BMJ Open Is Committed to Open Peer Review. As Part of This Commitment We Make the Peer Review History of Every Article We Publish Publicly Available

BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from

BMJ Open is committed to open peer review. As part of this commitment we make the peer review history of every article we publish publicly available.

When an article is published we post the peer reviewers’ comments and the authors’ responses online. We also post the versions of the paper that were used during peer review. These are the versions that the peer review comments apply to.

The versions of the paper that follow are the versions that were submitted during the peer review process. They are not the versions of record or the final published versions. They should not be cited or distributed as the published version of this manuscript.

BMJ Open is an open access journal and the full, final, typeset and author-corrected version of record of the manuscript is available on our site with no access controls, subscription charges or pay-per-view fees (http://bmjopen.bmj.com).

If you have any questions on BMJ Open’s open peer review process please email [email protected] http://bmjopen.bmj.com/ on September 23, 2021 by guest. Protected copyright. BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from

Rationale and Design of the Improving Care for Cardiovascular Disease in China (CCC) Project: A National Registry to Improve Management of Atrial Fibrillation

ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2017-020968

Article Type: Protocol

Date Submitted by the Author: 12-Dec-2017

Complete List of Authors: Hao, Yongchen; Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Department of Epidemiology Liu, Jing; Beijing Anzhen Hospital, Capital Medical University;Beijing Institute of Heart, Lung & Blood Vessel Diseases , Department of Epidemiology Smith, Sidney; University of North Carolina, Division of Cardiology Huo, Yong ; Peking University First Hospital, Department of Cardiology Fonarow, Gregg; University of California Los Angeles, Divisions of Cardiology Ge, Junbo; Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Department of Cardiology Liu, Jun; Beijing Anzhen Hospital, Capital Medical University, Beijing http://bmjopen.bmj.com/ Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China, Department of Epidemiology Taubert, Kathryn; American Heart Association, Department of Global Strategies Morgan, Louise; American Heart Association, International Quality Improvement Department Guo, Yang; Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China,

Department of Epidemiology on September 23, 2021 by guest. Protected copyright. Zhou, Mengge; Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China, Department of Epidemiology Zhao, Dong; Beijing Anzhen Hospital, Capital Medical University;Beijing Institute of Heart, Lung & Blood Vessel Diseases , Department of Epidemiology Ma, Chang-Sheng; Beijing AnZhen Hospital, Capital Medical University, Department of Cardiology

Keywords: Atrial fibrillation, quality improvement, healthcare, registry study

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Rationale and Design of the Improving Care for Cardiovascular Disease in 4 5 6 China (CCC) Project: 7 8 A National Registry to Improve Management of Atrial Fibrillation 9 10 1 1 2 3 4 11 Yongchen Hao, Jing Liu, Sidney C. Smith Jr, Yong Huo, Gregg C. Fonarow,

12 5 1 6 7 1 13 Junbo Ge, Jun Liu, Kathryn A. Taubert, Louise Morgan, Yang Guo, Mengge 14 1 1 8 15 Zhou, Dong Zhao, *Changsheng Ma, on behalf of the CCCAF Investigators 16 For peer review only 17 18 19 1 Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, 20 21 Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China 22 23 2 24 Division of Cardiology, University of North Carolina, USA 25 3 26 Department of Cardiology, Peking University First Hospital, China 27 4 28 Divisions of Cardiology, University of California, Los Angeles, CA, USA 29 30 5 Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, 31 32 Zhongshan Hospital, Fudan University, China http://bmjopen.bmj.com/ 33 34 6 Department of Global Strategies, American Heart Association, Switzerland 35 36 7 International Quality Improvement Department, American Heart Association, USA 37 38 8 39 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University,

40 on September 23, 2021 by guest. Protected copyright. 41 Beijing, China 42 43 44 45 Short title: Rationale and Design of CCCAF 46 47 48 49 50 51 52 53 54 55 56 57 1 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 4 5 * Corresponding author: 6 7 Dr. Changsheng Ma 8 9 Department of Cardiology, 10 11 Beijing Anzhen Hospital, Capital Medical University, 12 13 14 No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China. 15 16 Tel: +861064456412For peer review only 17 18 Fax: +861064456078 19 20 Email: [email protected]. 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 2 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Abstract 4 5 Introduction: Inadequate management of patients with atrial fibrillation (AF), the 6 7 commonest sustained arrhythmia, has been reported in China for anticoagulation 8 9 therapy and treatment for concomitant diseases. An effective quality improvement 10 11 program has been lacking to promote the use of evidencebased therapies and 12 13 14 improve outcome in patients with AF. 15 16 Methods andFor analysis: peer The Improving review Care for Cardiovascular only Disease in China 17 18 19 (CCC)AF program is a collaboration of the American Heart Association and the 20 21 Chinese Society of Cardiology. This program was designed to improve adherence to 22 23 AF guidelines and clinical outcomes for hospitalized patients with AF in China. 24 25 Launched in February 2015, 150 hospitals were recruited by geographiceconomic 26 27 regions across 30 provinces in China. Each month, 1020 inpatients with AF are 28 29 enrolled in each hospital. A webbased data collection platform is used to collect 30 31

32 clinical information for patients with AF, including patients’ demographics, http://bmjopen.bmj.com/ 33 34 admission information, medical history, inhospital care and outcomes, and discharge 35 36 medications for managing AF. The quality improvement initiative included monthly 37 38 benchmarked reports on hospital quality, training sessions, regular webinars, and 39 40 recognition of hospital quality achievement. Primary analyses will include adherence on September 23, 2021 by guest. Protected copyright. 41 42 to performance measures and guidelines. A generalized estimating equation model 43 44 45 was used to account for withinhospital correlation when sitespecific variance was a 46 47 concern. As of March 2017, 28 801 AF inpatients have been enrolled. 48 49 Ethics and dissemination: The study protocol was approved by the Ethics 50 51 52 Committee of Beijing Anzhen Hospital, Capital Medical University. Results will be 53 54 published in peerreviewed medical journals. 55 56 57 3 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Trial registration: NCT02309398 (www.clinicaltrials.gov). 4 5 6 Key words: Atrial fibrillation, quality improvement, healthcare, registry study 7 8 9 10 11 Strengths and limitations of this study 12 13 14 • CCCAF is a national hospitalbased quality improvement program with unique 15 16 tools includingFor monthlypeer benchmarked review reports ononly hospital quality, training 17 18 sessions, regular webinars, and recognition of hospital quality achievement. 19 20 • Data accuracy and completeness in this study is ensured by training sessions, 21 22 23 standardized webbased data collection platform, onsite quality control and 24 25 monitoring of data completeness. 26 27 • Experience from this program will help to guide development of the national 28 29 health quality improvement system. 30 31 • Participation is voluntary and only tertiary hospitals were recruited in the 32 http://bmjopen.bmj.com/ 33 CCCAF program. 34 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 4 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 INTRODUCTION 4 5 Atrial fibrillation (AF) is the commonest sustained arrhythmia and responsible for 6 7 major morbidity and health care costs. It is associated with a 4–5fold increased risk 8 9 for stroke, a 40%–90% increased risk for overall mortality, and impaired quality of 10 11 life.12 The prevalence of AF is estimated to be 0.77% in China, and more than 5 12 13 36 14 million Chinese adults aged older than 35 years currently have AF. There is wide 15 16 availability ofFor evidencebased peer guidelines review with effective treatmentsonly for improving 17 18 outcomes of AF.79 However, studies have indicated that there is low compliance with 19 20 evidencebased therapies in China, including assessment of thromboembolic risk, 21 22 anticoagulation therapy, heart rate control, rhythm control, and adequate treatment of 23 24 concomitant diseases.10,11 Multiple studies using a range of methodologies have 25 26 27 consistently documented that over 60% of patients who are candidates for 28 1013 29 anticoagulant therapy do not receive appropriate risk stratification or therapy. 30 31

32 Although previous registries have expanded understanding of clinical practice of http://bmjopen.bmj.com/ 33 34 AF in China, they have been limited in the representativeness of hospitals and lack of 35 10,12,13 36 quality improvement components. To promote the use of guidelines of 37 38 recommended therapies and to evaluate the effectiveness of quality improvement 39 40 efforts in China, the American Heart Association (AHA) and the Chinese Society of on September 23, 2021 by guest. Protected copyright. 41 42 Cardiology (CSC) launched the Improving Care for Cardiovascular Disease in China 43 44 45 (CCC) project – AF program. The CCCAF was modeled in part of the AHA Get

46 14 47 With The Guidelines (GWTG) program. It focuses on quality improvement efforts 48 49 with timely feedback for care of patients with AF. This program will advance the 50 51 quality of AF care by providing unique tools for quality improvement, following 52 53 trends in the adoption of evidencebased therapies in routine clinical practice, and by 54 55 observational treatment comparisons. 56 57 5 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 6 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 The purpose of this paper is to describe the objectives, organizational framework, 4 5 recruitment of hospitals and patients, data collection and management, quality control 6 7 of data collection, quality improvement tools for AF care, and progress to date of the 8 9 CCCAF program. 10 11 12 METHODS AND ANALYSIS 13 14 15 Study objectives 16 For peer review only 17 18 The overall objective of the CCCAF program is to improve patient care for AF by 19 20 development and implementation of quality improvement tools. This program aims to 21 22 promote the use of evidence‐based guidelines throughout the healthcare system and 23 24 improve cardiovascular health, using rapid cycle of data collection, analysis, feedback, 25 26 and process improvement. The specific aims of the CCCAF program are to: (1) 27 28 29 understand the current situation and main problems for management of patients 30 31 hospitalized with AF in China; (2) evaluate the effectiveness of the continuous quality

32 http://bmjopen.bmj.com/ 33 improvement efforts on the quality of care and outcomes of AF; and (3) explore and 34 35 optimize quality improvement strategies for care of AF in China. The timing and 36 37 dynamic monitoring of AF management will provide an opportunity to identify the 38 39 potential needs of further evidence in management of AF. Experience from this 40 on September 23, 2021 by guest. Protected copyright. 41 42 program may also help to guide development of the national health quality 43 44 improvement system and provide a blueprint for adaptation to other regions of the 45 46 world. 47 48 49 50 51 Organizational framework 52 53 54 As a collaborative program of the AHA and the CSC, the CCCAF is implemented by 55 56 the Beijing Institute of Heart, Lung and Blood Vessel Diseases. AHA secures the 57 6 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 7 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 project funding and CSC provided hospital network for CCCAF. As a continues 4 5 quality improvement program launched in February 2015, CCCAF has secured its 6 7 funding up to December 2018 currently. This program consists of a senior 8 9 management group (SMG) and a project management group. The senior management 10 11 group comprises 6 volunteer senior clinician leaders from AHA (Prof. Smith, Prof. 12 13 14 Fonarow and Prof. Taubert) and CSC (Prof. Huo, Prof. Ge and Prof. Ma). The SMG 15 16 members communicateFor peer frequently via review teleconference, emails only and facetoface meeting 17 18 to ensure the scientific integrity and supervise the implementation of CCCAF 19 20 program. The project management group is led by an international director (Ms. 21 22 Morgan) and a national director (Prof. Zhao), and oversees the daytoday 23 24 development and implementation of the program. There are 4 subgroups under the 25 26 27 management of a project coordinator (Prof. Jing Liu), including daytoday 28 29 management (Ms. Jun Liu and Ms. Zhou), data (Dr. Hao and Ms. Guo), and advisory 30 31 and education groups. Data collection and analysis are managed by daytoday

32 http://bmjopen.bmj.com/ 33 management group and data group, with guidance from SMG. 34 35 36 Hospital recruitment 37 38 39 Because hospital volumes and clinical capacities differ among geographic and

40 on September 23, 2021 by guest. Protected copyright. 41 economic regions, we recruited hospitals that are stratified by geographiceconomic 42 43 regions15. Mainland China includes 7 geographical regions: Northern, Northeast, 44 45 Eastern, Central, Southern, Southwest, and Eastern China. In each geographical region, 46 47 provinces are grouped into low, mediumlow, mediumhigh, and high levels according 48 49 to gross domestic product per capita. A detailed hospital sampling frame is shown in 50 51 52 Supplemental Table 1. In each geographiceconomic region, 10% of the tertiary 53 54 hospitals were recruited for our study in a voluntary manner, with a total of 150 55 56 hospitals. We prioritized tertiary hospitals that met specific criteria as follows: (1) the 57 7 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 8 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 average AF inpatient number per month was no less than 10; and (2) the director of the 4 5 Cardiology Department was willing to participate in the program. Traditional Chinese 6 7 medicine hospitals and specialized hospitals without cardiology wards were not 8 9 included in CCCAF program. The 150 hospitals were recruited in 2 phases. Hospitals 10 11 that were recruited in phases 1 and 2 are listed in Supplemental Table 2 and 12 13 14 Supplemental Table 3. 15 16 Patient recruitmentFor peer review only 17 18 19 In each hospital, the first 1020 AF inpatient cases of each month were consecutively 20 21 enrolled in the study, as identified based on discharge diagnosis through review of the 22 23 24 inpatient list. Study inclusion of AF was based on electrocardiograph results, which 25 26 were documented by 12lead electrocardiogram, 24hour Holter monitoring, or other 27 28 cardiac rhythm monitors. Patients with AF secondary to reversible condition (eg, 29 30 untreated thyroid disease and pulmonary embolism) were excluded from the study. 31 32 Clinical data elements were collected based on American College of Cardiology http://bmjopen.bmj.com/ 33 34 (ACC)/AHA recommendations on the clinical data standard for AF.16,17 As a quality 35 36 improvement initiative, the CCCAF program has high priority for collection of data 37 38 39 elements that are involved in assessment for quality of care. Moreover, additional data

40 on September 23, 2021 by guest. Protected copyright. 41 elements were gathered to facilitate indepth analysis. Data elements included 42 43 patients’ demographics, admission information, medical history, inhospital care and 44 45 outcomes, and discharge medications for management of AF. The case report form is 46 47 shown in Supplemental Table 4 (online only data supplement). Participating hospitals 48 49 were instructed to submit data for consecutive eligible patients to the CCCAF 50 51 52 database via a webbased data collection platform (Oracle Clinical Remote Data 53 54 Capture, Oracle Corporation). Each hospital assigned a data abstractor who was 55 56 responsible for data collection and entering the data elements abstracted from medical 57 8 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 9 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 charts. Online data entry for cases that were recruited for a particular month was 4 5 finished before the middle of the following month. 6 7 8 Quality control of data collection 9 10 18 11 Similar to the CCCAcute Coronary Syndrome (ACS) program, data accuracy and 12 13 completeness of the CCCAF program were ensured by the following 4 strategies. (1) 14 15 Training sessions were held before the launch of the program with itembyitem 16 For peer review only 17 explanations for all data elements. (2) The standardized webbased data collection 18 19 platform has automatic data checks and queries. (3) Data accuracy was also secured 20 21 by onsite quality control by thirdparty clinical research associates. Recruited cases 22 23 24 were compared with the inpatient list to ensure that cases were reported 25 26 consecutively rather than selectively, and 5% of reported cases were randomly 27 28 selected and compared with the original medical records. (4) Data completeness was 29 30 calculated as number of data elements filled in the database divided by number of 31 32 data elements that should be filled. Each month, data completeness was monitored http://bmjopen.bmj.com/ 33 34 and reports were provided as feedback to hospitals. For hospitals with data 35 36 completeness less than 90%, local investigators were contacted to improve quality of 37 38 39 data.

40 on September 23, 2021 by guest. Protected copyright. 41 Performance measures 42 43 44 Performance measures were developed to evaluate the quality of care for inpatients 45 46 with AF in the CCCAF program. These performance measures were constructed 47 48 1921 49 based on the statement of the ACC/AHA on AF performance measures 50 51 integrating recommendations from the most updated ACC/AHA guideline and 52 7,22 53 Chinese statement for AF. The quality of care presented in the monthly reports 54 55 was defined as primary and secondary performance measures. There are 6 primary 56 57 9 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 10 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 performance measures, including assessment of thromboembolic risk, anticoagulant 4 5 drug at discharge, prothrombin time (PT)/ international normalized ratio (INR) 6 7 planned followup, angiotensinconverting enzyme inhibitor (ACEI)/ angiotensin 8 9 receptor blocker (ARB) at discharge, betablockers at discharge, and statins at 10 11 discharge in AF inpatients with indications (Table 1). The full measure specifications 12 13 14 are shown in Supplemental Table 5. Eight secondary performance measures are 15 16 shown in TableFor 2 with theirpeer full measure review specifications shownonly in Supplemental Table 17 18 6. Measurespecific inclusion and exclusion criteria were applied so that only eligible 19 20 patients without documented intolerance or other contraindications for that specific 21 22 measure were included in the denominator. 23 24 25 The hospital composite score for primary performance measures was calculated in 26 27 an opportunitybased manner. This score was defined as the sum of total instances for 28 29 correct care given divided by the total number of eligible opportunities based on the 6 30 31 23

32 primary measures. Each patient at a CCCAF hospital contributes care opportunities http://bmjopen.bmj.com/ 33 34 to the relevant hospital’s composite performance scores. In the same way, the 35 36 composite score for secondary performance measures was calculated based on 8 37 38 secondary performance measures. 39

40 on September 23, 2021 by guest. Protected copyright. 41 The CCC team will update the performance measures and keep them aligned with 42 43 the new or updated clinical guidelines for management of AF when necessary. After 44 45 the new or updated AF guidelines are released, clinical experts will evaluate whether 46 47 applying these changes in guidelines to CCCAF performance measures and data 48 49 elements associated with them in the case report form is necessary. When changes are 50 51 52 adopted in the performance measures, hospitals have a transition period that allows 53 54 them to have flexibility in meeting recognition criteria for the updated performance 55 56 measures. 57 10 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 11 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Quality improvement tools 4 5 6 Improvement in adherence to guideline recommendations was facilitated through 7 8 monthly hospital quality reports, recognition of hospitals for achievement, training 9 10 programs, and online educational materials. 11 12 13 Monthly hospital quality reports 14 15 Each month, hospitals received quality reports on performance measures for AF via 16 For peer review only 17 18 online platform, accessed with a username and password. The content of hospital 19 20 quality reports included individual and composite scores for primary and secondary 21 22 performance measures, as well as data completeness of the reported AF cases. 23 24 Hospitalspecific data were summarized and compared against a variety of internal 25 26 and external benchmarks. Internal benchmarks included the trend of performance 27 28 measures over time. External benchmarks provided reasonable national performance 29 30 31 thresholds to help identify areas for potential improvement of performance. Two

32 http://bmjopen.bmj.com/ 33 external benchmarks were provided: overall national benchmarks and an achievable 34 35 benchmark of care that describes the composite guidelinerecommended treatment 36 37 provided at topperforming hospitals (e.g., the top 15%). These benchmarking quality 38 39 reports helped hospitals to identify areas for improvement and refine treatment 40 on September 23, 2021 by guest. Protected copyright. 41 processes to ensure they are in line with the guidelines. Frequencies of website visits 42 43 44 and downloads were tracked to evaluate engagement of each participating hospital. 45 46 Regional workshops 47 48 49 Regional workshops corresponding with CSC regional meetings occurred once or 50 51 twice per year to summarize progress, share experiences, discuss the problems that 52 53 may be encountered, and introduce stateoftheart evidencebased medicine and 54 55 56 clinical guidelines. These facetoface meetings served as venues where the 57 11 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 12 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 knowledge were shared, with discussion forums enabling delegates to identify 4 5 personal and local actions needed to improve clinical practice for AF. Educational 6 7 materials, such as flyers, pamphlets, or pocket guidelines, and measures with 8 9 CCCAF program branding were distributed to participating hospitals. 10 11 12 Hospital recognition 13 14 15 Hospitals demonstrating best practice received recognition through an announcement 16 For peer review only 17 ceremony at CSC annual meetings. There were 6 levels of recognition: gold, silver, 18 19 and bronze medals for AF performance measures, and awards for data reports, 20 21 progress, and active participation. Qualification criteria for recognition were the 22 23 18 24 same as those in the CCCACS program. Hospitals with best practice shared their 25 26 processes behind the achievement of good clinical practice for AF. 27 28 Online educational materials 29 30 31 The CCC websites provided a variety of online educational materials in the education 32 http://bmjopen.bmj.com/ 33 source center for healthcare professionals in the participating hospitals to view and 34 35 36 download. These webbased training materials included updated clinical guidelines 37 38 and scientific statements for AF and webinars. 39

40 on September 23, 2021 by guest. Protected copyright. Data management 41 42 43 All data were treated as protected health information and securely stored in a 44 45 passwordprotected computer system at the coordinating center. Ongoing data 46 47 48 cleaning was performed systematically. Data managers regularly queried data for 49 50 invalid and illogical values, identifying potential invalid values by searching for 51 52 outliers in continuous data distributions. When a potential error was detected, data 53 54 managers traced and reviewed the relevant records to resolve the issue. 55 56 57 12 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 13 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Statistical considerations 4 5 6 Recruitment of 1500 patients (10 in each of the 150 hospitals) with AF per month will 7 8 detect an improvement in the primary composite score from 45% at baseline to an 9 10 expected score of 51%, with 91% power at a significance level of 0.05 at a twosided 11 12 test. The projected 6% improvement (from 45% to 51%) in primary composite score 13 14 means that more 6% guideline recommended treatments will be correctly given for 15 16 AF patients. ForContinuous peer variables were review expressed as mean only ± SD or median 17 18 19 (interquartile range) and categorical variables as frequency and percentage. Missing 20 21 data were addressed on an analysisspecific basis. The chisquare trend test was 22 23 performed to evaluate the temporal trend of performance measures. Univariate and 24 25 multivariable approaches were used to identify factors associated with measures of 26 27 interest, including the use of guidelineindicated therapies and inhospital clinical 28 29 outcomes. Associations between patients’ characteristics and outcomes of interest 30 31

32 were reported with odds ratios and 95% confidence intervals using logistic regression. http://bmjopen.bmj.com/ 33 34 Multivariable adjustments were used to limit the influence of confounding factors. 35 36 Additionally, a generalized estimating equation model was used to account for 37 38 withinhospital correlation when sitespecific variance was a concern. A twosided P 39 40 value < 0.05 was considered statistically significant. Statistical analyses were on September 23, 2021 by guest. Protected copyright. 41 42 performed by SAS 9.2 (SAS Institute, Inc., Cary, NC) 43 44 45 Progress to date 46 47 48 In total, 150 public tertiary hospitals were recruited into the program, with 75 centers 49 50 in each of the 2 phases. Among them, 96 (64%) hospitals were from provincial 51 52 capitals and municipalities, while the other 54 (36%) were from prefecture level 53 54 cities (regional cities). The locations of participating centers are displayed in Figure 1. 55 56 57 13 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 14 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 A total of 28,801 AF inpatients were recruited from February 2015 to March 2017. 4 5 Table 3 shows the baseline demographic and clinical characteristics of the overall 6 7 population. The mean age of the population was 68.6 years and 15,738 (54.6%) were 8 9 men. Hypertension was the most prevalent concomitant disease, with a prevalence of 10 11 65.4%, followed by coronary artery disease (31.4%), heart failure (20.1%), and 12 13 14 diabetes mellitus (17.9%). 15 16 The overallFor quality peerof care for the review cohort of patients enrolledonly to date by the 17 18 19 composite performance measure score was 46.8%. The quality of care varied 20 21 between hospitals (Figure 2), with a wide range of composite scores ranging from 22 23 8.2% to 89.4% for primary performance measures. The composite score of the AF 24 25 secondary performance measures for all hospitals was 51.4%, with a wide range of 26 27 1.8%–96.2% (Figure 3). Adherence rates to each of the primary and secondary 28 29 performance measures are presented in Table 1 and Table 2. Data for quality reports 30 31

32 were exported for analysis each month, and quality reports were uploaded on the http://bmjopen.bmj.com/ 33 34 CCC website (www.cccheart.com). AF quality reports for February 2015 to March 35 36 2017 have been uploaded to the website. 37 38 39 DISCUSSION

40 on September 23, 2021 by guest. Protected copyright. 41 The growing AF population and increased recognition of mortality, morbidity, 42 43 diminished quality of life, and high healthcare costs associated with AF have led to 44 45 development of more effective treatments for AF and its complications. Currently, 46 47 there are several evidencebased, highly effective, guidelines of recommended 48 49 therapies that can significantly improve longterm care outcomes. The AHA, ACC, 50 51 52 and European Society of Cardiology (ESC) have compiled these therapies into 53 7,8 54 published guidelines. Despite the wide availability of these guidelines, studies have 55 56 indicated that there is low compliance with evidencebased therapies in China, even 57 14 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 15 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 10,11 3 among tertiary hospitals. Reasons for low compliance to guidelinebased therapies 4 5 include a lack of timely feedback, poor communication, and a lack of knowledge, 6 7 financial resource, or time.24,25 8 9 10 Accordingly, a variety of methods for increasing adherence to guidelines have 11 12 been initiated. Among them, three methods are widely used, which are increasing 13 14 reporting of the data, providing incentives to improve guideline adherence, and 15 16 providing hospitalsFor and peer physicians with review the tools and infrastructure only that necessary to 17 18 26 19 increase adherence. In 2008, the National Health and Family Planning Commission 20 21 of China launched a project for quality management of single diseases for acute 22 23 myocardial infarction, heart failure, and coronary artery bypass grafting. This project 24 25 aimed to enhance the reporting of these diseases and promote improvement in 26 27 quality.27 However, reporting without timely feedback and a lack of necessary 28 29 infrastructure for quality improvement prevented quality management of this single 30 31

32 diseases program from effective improvement in care. http://bmjopen.bmj.com/ 33 34 Previous registry studies have provided information on treatment and outcomes 35 36 for patients with AF in China (Table 4) 10,12,13,2831 and worldwide.3135 Zhang et al 37 38 10 39 enrolled 2016 patients with AF in 20 hospitals from 2008 to 2011. Among patients

40 on September 23, 2021 by guest. Protected copyright. 41 with nonvalvular AF, only 12.7% of those with a CHADS2 score of ≥2 were 42 43 prescribed oral anticoagulants, and this percentage was much lower than that in 44 45 developed countries reported by international registries.32,3639 As an ongoing registry, 46 47 the Chinese Atrial Fibrillation Registry was launched in 2011 with an enrollment goal 48 49 of 20,000 patients with AF in 32 hospitals in Beijing, with a followup of every 6 50 51 12 52 months until 2020. Although these registries have expanded understanding for 53 54 clinical practice and longterm outcomes of AF, they have been limited in a finite 55 56 number of hospitals and lack of quality improvement components. 57 15 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 16 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 In 2014, the AHA and CSC launched the CCCAF program, aiming to improve 4 5 quality of care for AF with timely feedback and quality improvement tools. The 6 7 CCCAF program is similar to the CCCacute coronary syndrome program.18 This 8 9 program will provide important national data for the characteristics and care of AF 10 11 inpatients. Through iterative assessment of guidelinebased care, the CCCAF 12 13 14 program provides opportunities for improving adherence to clinical practice 15 16 guidelines andFor other performance peer measures review at a hospital onlylevel. Performance feedback 17 18 reports may help hospitals to identify opportunities to improve patient care across a 19 20 broad range of performance measures. This program provides specific resources, such 21 22 as webinars and regional workshops to address the identified gaps. The CCCAF 23 24 program will also help in tracking the rate of diffusion of new knowledge and the 25 26 27 adoption of new guideline recommendations, highlighting areas for further quality 28 29 improvement. 30 31

32 The CCCAF program aims to improve adherence to guideline recommendations http://bmjopen.bmj.com/ 33 34 through monthly benchmarked hospital quality reports, recognition of achievement of 35 36 hospital quality, training programs, and regular webinars. As shown in the improve 37 38 treatment with oral anticoagulants in atrial fibrillation (IMPACTAF) study, 39 40 multifaceted educational intervention significantly increased the proportion of patients on September 23, 2021 by guest. Protected copyright. 41 42 treated with oral anticoagulants and has the potential to improve stroke prevention for 43 44 40 45 patients with AF. Currently, guidelinebased therapies for AF mainly focus on 46 47 antithrombotic management, rate and rhythm control, and therapy of concomitant 48 49 cardiac diseases. For antithrombotic management, risk stratification is an essential 50 51 step for recognizing candidate patients for therapy and deciding which patients have 52 53 sufficient risk to warrant oral anticoagulation. Quality improvement tools of the 54 55 CCCAF program are designed to prompt assessment of thromboembolic risk based 56 57 16 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 17 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 on easily used risk stratification scores, as well as the use of anticoagulant drugs at 4 5 discharge, PT/INR planned followup, and therapy of concomitant cardiac diseases 6 7 using ACEIs/ARBs, betablockers, and statins at discharge in patients with AF and 8 9 indications. Because patients with AF are usually admitted with concomitant 10 11 cardiovascular diseases, careful consideration of coprescription of anticoagulants 12 13 14 with antiplatelet therapy is warranted, balancing the bleeding risk and stroke risk. The 15 16 CCCAF programFor will peerprovide important review insight for patterns only of current clinical practice 17 18 for patients with AF and concomitant cardiovascular diseases (e.g., ACS) and 19 20 procedures (e.g., percutaneous coronary intervention). 21 22 23 The CCCAF program is distinguished by its unique resources, which include a 24 25 large hospital network and an international research team. These will facilitate the 26 27 translation of study findings to improvement of quality care for AF. Tertiary hospitals 28 29 provide the highest level of medical care in China, and affect secondary hospitals and 30 31

32 primary care centers. Improvement in the quality of care for AF among these tertiary http://bmjopen.bmj.com/ 33 34 hospitals may lead to spreading their experience to secondary hospitals and primary 35 36 care centers and enhance the dissemination of evidencebased interventions. 37 38 39 There are several limitations that should be mentioned. Participation is voluntary

40 on September 23, 2021 by guest. Protected copyright. 41 and only tertiary hospitals were recruited in the CCCAF program. The current 42 43 participating hospital profile tends to be that larger centers may have better baseline 44 45 performance than smaller centers possessing fewer resources. While participating 46 47 hospitals are instructed to include all consecutive AF admissions, identifying patients 48 49 with AF uniformly and accurately can be challenging, so there is the potential for 50 51 52 selection bias. Patient data are collected by medical chart review and thus dependent 53 54 on the quality, accuracy, and completeness of documentation. The inpatient focus of 55 56 the CCCAF program is a further limitation. The ability to track patients over time is 57 17 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 18 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 necessary to develop a more thorough understanding of downstream resource use, as 4 5 well as outcomes associated with specific therapies and procedures. Collection of 6 7 followup information and linking with administrative outcome databases will further 8 9 promote research on effectiveness of this project for improving quality. Also, results 10 11 presented here are preliminary and should be interpreted with caution. 12 13 14 As a national hospitalbased quality improvement program, CCCAF aims to 15 16 provide an opportunityFor peer to improve adherence review to clinical practiceonly guidelines for 17 18 managing AF. This program has unique tools for quality improvement which could 19 20 improve patients’ outcomes. 21 22 23 Ethics and dissemination 24 25 26 Central institutional review board (IRB) approval was granted for the aggregate 27 28 dataset for research and quality improvement by the Ethics Committee of Beijing 29 30 Anzhen Hospital, Capital Medical University. Participating sites were granted a 31 32 waiver of patient consent under the common rule. One hundred and eleven hospitals http://bmjopen.bmj.com/ 33 34 accepted central ethics approval and the other 39 sites applied IRB approval from 35 36 their own ethics committees. The study is listed at www.clinicaltrials.gov 37 38 39 (NCT02309398). Results will be published in peerreviewed medical journals.

40 on September 23, 2021 by guest. Protected copyright. 41 Acknowledgments 42 43 44 The authors acknowledge all participating hospitals for their contribution to the 45 46 program. Complete lists of participating hospitals and principal investigators are 47 48 49 provided in Supplemental Tables 2 and 3. 50 51 52 53 54 55 56 57 18 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 19 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 REFERENCES 4 5 6 1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for 7 8 stroke: the Framingham Study. Stroke. 1991;22:983988. 9 2. Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact 10 11 of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 12 13 1998;98(10):946952. 14 15 3. Hu D, Sun Y. Epidemiology, risk factors for stroke, and management of atrial 16 For peer review only 17 fibrillation in China. J Am Coll Cardiol. 2008;52:865868. 18 19 4. Zhou Z, Hu D, Chen J, Zhang R, Li K, Zhao X. An epidemiological survey of atrial 20 21 fibrillation in China. Chinese Journal of Internal Medicine. 2004;43:491494. 22 23 5. Li Y, Wu YF, Chen KP, et al. Prevalence of atrial fibrillation in China and its risk 24 25 factors. Biomed Environ Sci. 2013;26(9):709716. 26 27 6. Guo Y, Tian Y, Wang H, Si Q, Wang Y, Lip GY. Prevalence, incidence, and lifetime 28 29 risk of atrial fibrillation in China: new insights into the global burden of atrial 30 31 fibrillation. Chest. 2015;147(1):109119. 32 http://bmjopen.bmj.com/ 33 7. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the 34 35 management of patients with atrial fibrillation: executive summary: a report of the 36 37 American College of Cardiology/American Heart Association Task Force on practice 38 39 guidelines and the Heart Rhythm Society. Circulation. 2014;130:2071 2104. 40 on September 23, 2021 by guest. Protected copyright. 41 8. Camm AJ, Kirchhof P, Lip GY, et al. Guidelines for the management of atrial 42 43 fibrillation: the Task Force for the Management of Atrial Fibrillation of the European 44 45 Society of Cardiology (ESC). Europace. 2010;12(10):13601420. 46 47 9. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of 48 49 atrial fibrillation developed in collaboration with EACTS: The Task Force for the 50 51 management of atrial fibrillation of the European Society of Cardiology (ESC) 52 53 Developed with the special contribution of the European Heart Rhythm Association 54 55 (EHRA) of the ESC Endorsed by the European Stroke Organization (ESO). Eur 56 57 19 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 20 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Heart J. 2016; 37: 2893–2962 4 5 10. Zhang H, Yang Y, Zhu J, et al. Baseline characteristics and management of patients 6 7 with atrial fibrillation/flutter in the emergency department: results of a prospective, 8 9 multicentre registry in China. Intern Med J. 2014;44:742748. 10 11 11. Zhang S. Atrial fibrillation in mainland China: epidemiology and current 12 13 management. Heart. 2009;95:10521055. 14 15 12. Chang SS, Dong JZ, Ma CS, et al. Current Status and Time Trends of Oral 16 For peer review only 17 Anticoagulation Use Among Chinese Patients With Nonvalvular Atrial Fibrillation: 18 19 The Chinese Atrial Fibrillation Registry Study. Stroke. 2016; 47:18031810 20 21 13. Xiong Q, Shantsila A, Lane DA, et al. Sex differences in clinical characteristics and 22 23 inpatient outcomes among 2442 hospitalized Chinese patients with nonvalvular atrial 24 25 fibrillation: The Nanchang Atrial Fibrillation Project. Int J Cardiol. 26 27 2015;201:195199. 28 29 14. Ellrodt AG, Fonarow GC, Schwamm LH, et al. Synthesizing lessons learned from get 30 with the guidelines: the value of diseasebased registries in improving quality and 31

32 http://bmjopen.bmj.com/ outcomes. Circulation. 2013;128:24472460. 33 34 15. National Bureau of Statistics of China. China Statistical Year book 2013. China 35 36 Statistics Press. Beijing, China. 2013. 37 38 16. McNamara RL, Brass LM, Drozda Jr JP, et al. ACC/AHA key data elements and 39

40 on September 23, 2021 by guest. Protected copyright. definitions for measuring the clinical management and outcomes of patients with 41 42 atrial fibrillation: A report of the American College of Cardiology/American Heart 43 44 Association Task Force on clinical data standards (writing committee to develop data 45 46 standards on atrial fibrillation). Journal of the American College of Cardiology. 47 48 2004;44:475495. 49 50 17. Buxton AE, Calkins H, Callans DJ, et al. ACC/AHA/HRS 2006 key data elements 51 52 and definitions for electrophysiological studies and procedures: a report of the 53 54 American College of Cardiology/American Heart Association Task Force on Clinical 55 56 Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on 57 20 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 21 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Electrophysiology). J Am Coll Cardiol. 2006;48:23602396. 4 5 18. Hao Y, Liu J, Liu J, et al. Rationale and Design of the Improving Care for 6 7 Cardiovascular Disease in China (CCC) Project: a National Effort to Prompt Quality 8 9 Enhancement for Acute Coronary Syndrome. American Heart Journal. 2016 10 11 ;179:10715 12 13 19. Spertus JA, Eagle KA, Krumholz HM, Mitchell KR, Normand SL. American College 14 15 of Cardiology and American Heart Association methodology for the selection and 16 For peer review only 17 creation of performance measures for quantifying the quality of cardiovascular care. 18 19 Circulation. 2005;111:17031712. 20 21 20. Estes NA, 3rd, Halperin JL, Calkins H, et al. ACC/AHA/Physician Consortium 2008 22 23 clinical performance measures for adults with nonvalvular atrial fibrillation or atrial 24 25 flutter: a report of the American College of Cardiology/American Heart Association 26 27 Task Force on Performance Measures and the Physician Consortium for Performance 28 29 Improvement (Writing Committee to Develop Clinical Performance Measures for 30 Atrial Fibrillation): developed in collaboration with the Heart Rhythm Society. 31

32 http://bmjopen.bmj.com/ Circulation. 2008;117(8):11011120. 33 34 21. Bonow RO, Douglas PS, Buxton AE, et al. ACCF/AHA methodology for the 35 36 development of quality measures for cardiovascular technology: a report of the 37 38 American College of Cardiology Foundation/American Heart Association Task Force 39

40 on September 23, 2021 by guest. Protected copyright. on Performance Measures. Circulation. 2011;124:14831502. 41 42 22. Huang C, Zhang S, Huang D, et al. Current knowledge and management 43 44 recommendations of atrial fibrillation: 2015. Chinese Journal of Cardiac 45 46 Arrhythmias. 2015(5):321385. 47 48 23. Eapen ZJ, Fonarow GC, Dai D, et al. Comparison of composite measure 49 50 methodologies for rewarding quality of care: an analysis from the American Heart 51 52 Association's Get With The Guidelines program. Circ Cardiovasc Qual Outcomes. 53 54 2011;4:610618. 55 56 24. Cabana MD, Rand CS, Powe NR, et al. Why don't physicians follow clinical practice 57 21 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 22 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 guidelines? A framework for improvement. JAMA. 1999;282:14581465. 4 5 25. Berthiaume JT, Tyler PA, NgOsorio J, LaBresh KA. Aligning financial incentives 6 7 with "Get With The Guidelines" to improve cardiovascular care. Am J Manag Care. 8 9 2004;10:501504. 10 11 26. Lewis WR, Peterson ED, Cannon CP, et al. An organized approach to improvement 12 13 in guideline adherence for acute myocardial infarction: results with the Get With The 14 15 Guidelines quality improvement program. Arch Intern Med. 2008;168:18131819. 16 For peer review only 17 27. Chinese Hospital Association. Manual of single disease quality management. 18 19 Scientific and technical documentation press, Beijing, China. 2008. 20 21 28. Sun Y, Wang Y, Jiang J, Wang L, Hu D. Renal Dysfunction, CHADS2 Score, and 22 23 Adherence to the Anticoagulant Treatment in Nonvalvular Atrial Fibrillation: A 24 25 CrossSectional Study in Mainland China. Clin Appl Thromb Hemost. 2015. 26 27 29. Sun Y, Hu D, Li K, Zhou Z. Predictors of stroke risk in native Chinese with 28 29 nonrheumatic atrial fibrillation: retrospective investigation of hospitalized patients. 30 Clin Cardiol. 2009;32:7681. 31

32 http://bmjopen.bmj.com/ 30. Lip GYH, RushtonSmith SK, Goldhaber SZ, et al. Does Sex Affect Anticoagulant 33 34 Use for Stroke Prevention in Nonvalvular Atrial Fibrillation?: The Prospective Global 35 36 Anticoagulant Registry in the FIELDAtrial Fibrillation. Circulation: Cardiovascular 37 38 Quality and Outcomes. 2015;8:S12S20. 39

40 on September 23, 2021 by guest. Protected copyright. 31. Huisman MV, Rothman KJ, Paquette M, et al. Antithrombotic Treatment Patterns in 41 42 Patients with Newly Diagnosed Nonvalvular Atrial Fibrillation: The GLORIAAF 43 44 Registry, Phase II. Am J Med. 2015;128:13061313 e1301. 45 46 32. Lip GY, Laroche C, Ioachim PM, et al. Prognosis and treatment of atrial fibrillation 47 48 patients by European cardiologists: one year followup of the EURObservational 49 50 Research ProgrammeAtrial Fibrillation General Registry Pilot Phase (EORPAF 51 52 Pilot registry). Eur Heart J. 2014;35:33653376. 53 54 33. Lewis WR, Piccini JP, Turakhia MP, et al. Get With The Guidelines AFIB: novel 55 56 quality improvement registry for hospitalized patients with atrial fibrillation. Circ 57 22 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 23 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Cardiovasc Qual Outcomes. 2014;7:770777. 4 5 34. Kakkar AK, Mueller I, Bassand JP, et al. International longitudinal registry of 6 7 patients with atrial fibrillation at risk of stroke: Global Anticoagulant Registry in the 8 9 FIELD (GARFIELD). Am Heart J. 2012;163):1319 e11. 10 11 35. Piccini JP, Fraulo ES, Ansell JE, et al. Outcomes registry for better informed 12 13 treatment of atrial fibrillation: Rationale and design of ORBITAF. American Heart 14 15 Journal. 2011;162:606612.e601. 16 For peer review only 17 36. Lamberts M, Gislason GH, Olesen JB, et al. Oral anticoagulation and antiplatelets in 18 19 atrial fibrillation patients after myocardial infarction and coronary intervention. J Am 20 21 Coll Cardiol. 2013;62:981989. 22 23 37. Piccini JP, Hernandez AF, Zhao X, et al. Quality of care for atrial fibrillation among 24 25 patients hospitalized for heart failure. J Am Coll Cardiol. 2009;54:12801289. 26 27 38. Steinberg BA, Kim S, Piccini JP, et al. Use and associated risks of concomitant 28 29 aspirin therapy with oral anticoagulation in patients with atrial fibrillation: insights 30 from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation 31

32 http://bmjopen.bmj.com/ (ORBITAF) Registry. Circulation. 2013;128:721728. 33 34 39. Wieloch M, Sjalander A, Frykman V, Rosenqvist M, Eriksson N, Svensson PJ. 35 36 Anticoagulation control in Sweden: reports of time in therapeutic range, major 37 38 bleeding, and thromboembolic complications from the national quality registry. Eur 39

40 on September 23, 2021 by guest. Protected copyright. Heart J. 2011;32:22822289. 41 42 40. Vinereanu D, Lopes RD, Bahit MC, et al. A multifaceted intervention to improve 43 44 treatment with oral anticoagulants in atrial fibrillation (IMPACTAF): an 45 46 international, clusterrandomised trial. Lancet. 2017 (in press) 47 48 https://doi.org/10.1016/S01406736(17)321657 49 50 51 52 53 54 55 56 57 23 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 24 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Authors’ contributions: 4 5 6 The manuscript was prepared on behalf of the CCCAF Investigators. SS, Y Huo, GF, 7 8 JG, KT, CM and DZ conceived the study idea. Jing L, Jun L, LM, YG and MZ made 9 10 substantial contributions to the development of the study protocol. Y Hao drafted the 11 12 manuscript and all authors contributed to critical revisions of the paper. This final 13 14 manuscript was read and approved by all authors. 15 16 For peer review only 17 Funding 18 19 The CCC project is a collaborative program of the AHA and the CSC. The AHA was 20 21 funded by Pfizer for the quality improvement initiative through an independent grant 22 23 24 for learning and change. Pfizer provided no oversight on the goals, execution, or 25 26 publication of the program. The authors are solely responsible for the design and 27 28 conduct of this study, all study analyses, the drafting and editing of the manuscript, 29 30 and its final contents. 31 32 Disclosures http://bmjopen.bmj.com/ 33 34 The authors declare that they have no competing interests. 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 24 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 25 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Figure Legends 4 5 6 Figure 1. Distribution of hospitals for the CCCAF program. 7 8 Numerals on the map indicate the number of hospitals in the area. Adapted from 9 10 11 reference 18. 12 13 14 15 Figure 2. Distribution of CCCAF composite scores of primary performance measures 16 For peer review only 17 across hospitals from February 2015 to March 2017. 18 19 The composite scores were calculated based on the 6 primary performance measures, 20 21 using the sum of total instances when a required measure was performed (correct care 22 23 24 provided) divided by the total number of eligible opportunities. 25 26 27 28 Figure 3. Distribution of CCCAF composite scores of secondary performance 29 30 measures across hospitals from February 2015 to March 2017. 31 32 The composite scores were calculated based on 8 secondary performance measures, http://bmjopen.bmj.com/ 33 34 using the sum of total instances when a required measure was performed (correct care 35 36 provided) divided by the total number of eligible opportunities. 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 25 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from Page 26 of 34

) ) 8857 3382 / / denominator) denominator)

7721 1794 (

1 Proportion,% Proportion,% 57.0 (1245/2184) 57.0 (1245/2184) 87.2 ( 53. 61.2 (8524/13925) 61.2 (8524/13925) 46.8 (31081/66362) 46.8 (31081/66362) 42.3 42.3 (6413/15150) 23.6 23.6 (5384/22864) (Numerator/

harge disc

up up planned

BMJ Open http://bmjopen.bmj.com/ VASc≥2 2 DS 2 on September 23, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

Title of Performance Measure Measure Performance Title of For peer review only Proportion of AF patients with indications receiving ACEI/ARB ACEI/ARB discharge at receiving with indications AF patients of Proportion Proportion of AF patients with indication prescribed a statin at discharge at discharge a statin prescribed with indication AF patients of Proportion Proportion of AF patients with indication prescribed an anticoagulant drug at discharge at discharge anticoagulant drug an prescribed with indication AF patients of Proportion discharge blocker at a beta prescribed with indication AF patients of Proportion Proportion of patients discharged on warfarin who have PT/INR follow PT/INR who have on warfarin of discharged patients Proportion b c d a Proportion of patients with nonvalvular AF in whom assessment of thromboembolic risk risk thromboembolic of assessment whom AF in of with nonvalvular patients Proportion Composite scores of primary performance measures measures performance scores primary of Composite indications refer to AF patients with AMI; or coronary heart disease with comorbidity of hypertension, diabetes mellitus or chronic kidney chronic kidney mellitus or diabetes comorbidity of hypertension, with heart disease coronary AMI; or patients with AF to refer indications indications refer to nonvalvular AF patients AF patients with CHA to nonvalvular refer indications

PT, prothrombin time; INR, international normalized ratio; ACEI, angiotensinconverting enzyme inhibitor; ARB, angiotensin receptor blocker. blocker. receptor angiotensin ARB, inhibitor; enzyme angiotensinconverting ACEI, ratio; normalized international INR, time; prothrombin PT, a b 2 3 4 1 Project the CCCAF for Measures Performance Primary 1. Table 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 27 27 BMJ Open http://bmjopen.bmj.com/ on September 23, 2021 by guest. Protected copyright.

For peer review only For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml indications refer to AF patients with coronary heart disease, ischemic stroke/TIA, peripheral vascular disease or diabetes mellitus. disease or diabetes vascular peripheral stroke/TIA, ischemic disease, heart coronary patients with AF to refer indications indications refer to AF patients with heart failure failure patients with heart AF to refer indications

disease; or LVEF<40% according to the case records. case records. the according to disease; or LVEF<40% c d 1 2 3 Page 27 of 34 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from Page 28 of 34

)

) ) 8266 12243 5623 10989 / / / /10 denominator) denominator)

1263 7140 ( 10941 (

55608 (

5 (

Proportion,% Proportion,% 4 72.2 (888/1230) 72.2 (888/1230) 22. 52.4 (2010/3838) 52.4 (2010/3838) 15.0 (3422/22864) 15.0 (3422/22864) 19.2 (4397/22864) 19.2 (4397/22864) 65. 1.4 88.3 (25547/28615) 88.3 (25547/28615) 89. 5 (Numerator/

28 28 of <80 bpm closest bpm closest to discharge <80 of BMJ Open

http://bmjopen.bmj.com/ VASc score reported score reported VASc 2 score reported score 2 DS 2

on September 23, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Title of Performance Measure TitleMeasure Performance of For peer review only primary performance measures performance primary Proportion of AF patients with indication prescribed aldosterone antagonist at discharge at discharge antagonist aldosterone prescribed indication with patients AF of Proportion indications refer to AMI patients with LVEF<40% or heart failure or diabetes mellitus; or the heart failure patients with LVEF<35%. patients failure heart or the mellitus; or diabetes failure heart or with LVEF<40% patients AMI to refer indications

Proportion of AF patients who have a documented resting rate heart resting documented a have patients who AF ofProportion education therapy anticoagulation patients that receiving AF ofProportion a counseling advice or cessation smoking are patients given who AF ofProportion scores of Composite Proportion of nonvalvular AF patients who had a CHA a had AF patients who of nonvalvular Proportion education medical conventional patients that receiving AF ofProportion Proportion of nonvalvular AF patients who had a CHADS a had AF patients who of nonvalvular Proportion Proportion valvular AF patients prescribed warfarin at discharge at discharge warfarin AF patients prescribed valvular Proportion AF, atrial fibrillation fibrillation atrial AF, a

Table 2. Secondary Performance Measures for the CCCAF CCCAF Project for the Measures Performance Table Secondary 2. 2 3 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 29 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 1 Table 3. Characteristics of Enrolled Patients with AF 4 5 6 Men Women Overall 7 8 n=15738 n=13063 n=28801 9 10 11 Age 12 13 mean (SD), y 67.0(12.7) 70.6(11.2) 68.6 (12.1) 14 15 Age group, n (%) 16 For peer review only 17 <65 y 6528(41.5) 3823(29.3) 10351(35.9) 18 19 6574 y 4512(28.7) 4079(31.2) 8591(29.8) 20 21 22 ≥75 y 4698(29.9) 5161(39.5) 9859(34.2) 23 24 Healthcare insurance, n (%) 25 26 Urban employeesbasic insurance 6823(43.4) 5045(38.6) 11868(41.2) 27 28 Urban residentsbasic insurance 2817(17.9) 2782(21.3) 5599(19.4) 29 30 New rural cooperative insurance 2696(17.1) 2830(21.7) 5526(19.2) 31 32 Selfpaying 1654(10.5) 1186(9.1) 2840(9.9) http://bmjopen.bmj.com/ 33 34 Others 1748(11.1) 1220(9.3) 2968(10.3) 35 36 37 Medical history, n (%) 38 39 Hypertension 9973(63.4) 8874(67.9) 18847(65.4)

40 on September 23, 2021 by guest. Protected copyright. 41 CAD 5050(32.1) 3991(30.6) 9041(31.4) 42 43 Heart failure 2994(19.0) 2788(21.3) 5782(20.1) 44 45 Diabetes mellitus 2694(17.1) 2473(18.9) 5167(17.9) 46 47 Stroke/TIA 2187(13.9) 1843(14.1) 4030(14) 48 49 50 PAD 1647(10.5) 915(7.0) 2562(8.9) 51 52 Myocardial infarction 1191(7.6) 551(4.2) 1742(6.0) 53 54 Previous bleeding 96(0.6) 74(0.6) 170(0.6) 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 30 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Current smoker 5241(33.3) 413(3.2) 5654(19.6) 4 5 AF type 6 7 Newly diagnosed 1742(11.1) 1330(10.2) 3072(10.7) 8 9 Paroxysmal 6143(39.0) 5053(38.7) 11196(38.9) 10 11 12 Persistent 4256(27.0) 3405(26.1) 7661(26.6) 13 14 Permanent 2447(15.5) 2327(17.8) 4774(16.6) 15 16 UnknownFor peer review1150(7.3) only 948(7.3) 2098(7.3) 17 18 19 1 AF, atrial fibrillation; SD, standard deviation; CVD, cardiovascular disease; CAD, 20 21 2 coronary artery disease; PCI, percutaneous coronary intervention; TIA, transient 22 23 3 ischemic attack; PAD, peripheral artery disease. 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 30 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from

2013 present

2011 2011

No 2 2 year Follow up up Follow period Study

QI QI No No measure measure

size size 2442 2016 2016 No 1 year 20082011 10871 Sample Sample

31 31 BMJ Open http://bmjopen.bmj.com/ Inpatient Outpatient

1 736 on September 23, 2021 by guest. Protected copyright.

42 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

For peer China only review only

China only 20 department Emergency 13 China only 50 Outpatient 3017 No No 2012 10 30 858 Outpatient/inpatient 17184 No 1 year 20102013

28 30 31 China only 18 Inpatient 3425 No No 20002004 29 China only 32 Outpatient/inpatient 11496 No Up 2020 to present 2011 12 AF AF II Studies Studies Countries Sites Population CAFR Sun al. et Sun GLORIA GARFIELDAF GARFIELDAF Sun Y et al. al. et 2015 Y Sun Chinese AF registry AF registry Chinese Nanchang AF AF Project Nanchang CAFR, Chinese Atrial Fibrillation Registry Study; GLORIAAF, Global Registry on Longterm Oral Antithrombotic Treatment in Patients with Patients in Treatment Antithrombotic on Oral Longterm Registry Global GLORIAAF, Study; Registry Fibrillation Atrial Chinese CAFR, improvement. quality QI, Fibrillation; FIELDAtrial in the Registry Anticoagulant Global GARFIELDAF, Fibrillation; Atrial Table 4. Characteristics of AF Registries Involving in China Sites Involving AF Registries of Characteristics Table 4.

2 3 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 31 of 34 BMJ Open Page 32 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 1 Figure 1 4 5 6 7 8 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 2 29 30 3 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 32 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 33 of 34 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 1 Figure 2 4 2 5 6 7 8 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 3 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 33 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 34 of 34 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 1 Figure 3. 4 2 5 6 7 8 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 3 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 34 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from

Rationale and Design of the Improving Care for Cardiovascular Disease in China (CCC) Project: A National Registry to Improve Management of Atrial Fibrillation

ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2017-020968.R1

Article Type: Protocol

Date Submitted by the Author: 03-Mar-2018

Primary Subject Cardiovascular medicine Heading:

Secondary Subject Heading: Epidemiology

Keywords: Atrial fibrillation, quality improvement, healthcare, registry study

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Rationale and Design of the Improving Care for Cardiovascular Disease in 4 5 6 China (CCC) Project: 7 8 A National Registry to Improve Management of Atrial Fibrillation 9 10 1 1 2 3 4 11 Yongchen Hao, Jing Liu, Sidney C. Smith Jr, Yong Huo, Gregg C. Fonarow,

12 5 1 6 7 1 13 Junbo Ge, Jun Liu, Kathryn A. Taubert, Louise Morgan, Yang Guo, Mengge 14 1 1 8 15 Zhou, Dong Zhao, *Changsheng Ma, on behalf of the CCCAF Investigators 16 For peer review only 17 18 19 1 Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical 20 21 University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 22 23 24 China 25 2 26 Division of Cardiology, University of North Carolina, Chapel Hill, NC, USA 27 3 28 Department of Cardiology, Peking University First Hospital, Beijing, China 29 30 4 Divisions of Cardiology, Geffen School of Medicine at University of California, Los 31 32 Angeles, CA, USA http://bmjopen.bmj.com/ 33 34 5 Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, 35 36 Zhongshan Hospital, Fudan University, Shanghai, China 37 38 6 39 Department of Global Strategies, American Heart Association, Basel, Switzerland

40 on September 23, 2021 by guest. Protected copyright. 7 41 International Quality Improvement Department, American Heart Association, 42 43 Dallas, TX, USA 44 45 8 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 46 47 Beijing, China 48 49

50 51 52 Short title: Rationale and Design of CCCAF 53 54 55 56 57 1 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 * Corresponding author: 4 5 Dr. Changsheng Ma 6 7 Department of Cardiology, 8 9 Beijing Anzhen Hospital, Capital Medical University, 10 11 No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China. 12 13 14 Tel: +861064456412 15 16 Fax: +861064456078For peer review only 17 18 Email: [email protected]. 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 2 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Abstract 4 5 Introduction: Inadequate management of patients with atrial fibrillation (AF) has 6 7 been reported in China for anticoagulation therapy and treatment for concomitant 8 9 diseases. An effective quality improvement program has been lacking to promote the 10 11 use of evidencebased treatments and improve outcome in patients with AF. 12 13 14 Methods and analysis: The Improving Care for Cardiovascular Disease in China 15 16 (CCC)AF programFor is apeer collaboration review of the American Heart only Association and the 17 18 19 Chinese Society of Cardiology. This program is designed to promote adherence to 20 21 AF guideline recommendations and outcomes for inpatients with AF. Launched in 22 23 February 2015, 150 hospitals are recruited by geographiceconomic regions across 24 25 30 provinces in China. Each month, 1020 inpatients with AF are enrolled in each 26 27 hospital. A webbased data collection platform is used to collect clinical information 28 29 for patients with AF, including patients’ demographics, admission information, 30 31

32 medical history, inhospital care and outcomes, and discharge medications for http://bmjopen.bmj.com/ 33 34 managing AF. The quality improvement initiative includes monthly benchmarked 35 36 reports on hospital quality, training sessions, regular webinars, and recognitions of 37 38 hospital quality achievement. Primary analyses will include adherence to 39 40 performance measures and guidelines. To address intrahospital correlation, on September 23, 2021 by guest. Protected copyright. 41 42 generalized estimating equation models will be applied. As of March 2017, 28 801 43 44 45 AF inpatients have been enrolled. 46 47 Ethics and dissemination: This study protocol was approved by the Ethics 48 49 Committee of Beijing Anzhen Hospital, Capital Medical University. Results will be 50 51 52 published in peerreviewed medical journals. 53 54 Trial registration: NCT02309398 (www.clinicaltrials.gov). 55 56 57 3 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Key words: Atrial fibrillation, quality improvement, healthcare, registry study 4 5 6 7 8 Strengths and limitations of this study 9 10 11 • CCCAF is a nationwide quality improvement project with tools including 12 13 monthly benchmarked reports on hospital quality, training sessions, regular 14 15 webinars, and recognition for quality achievement. 16 For peer review only 17 18 • Data accuracy and completeness of this study is ensured by training sessions, 19 20 standardized webbased data collection tool, onsite quality control and 21 22 monitoring of data completeness. 23 24 • Experience from this program will help to guide development of the national 25 26 health quality improvement system. 27 28 • Participation is voluntary and only tertiary hospitals are recruited in the CCCAF 29 30 31 program, which may not be able to represent the care quality for the China

32 http://bmjopen.bmj.com/ 33 overall. 34 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 4 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 6 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 INTRODUCTION 4 5 As the commonest sustained arrhythmia, atrial fibrillation (AF) is responsible for 6 7 major morbidity and health care costs. It is associated with a 4–5fold increased risk 8 9 for stroke, a 40%–90% increased risk for overall mortality, and impaired quality of 10 11 life.12 The prevalence of AF is estimated to be 0.77% in China, and more than 5 12 13 36 14 million Chinese adults aged older than 35 years currently have AF. There is wide 15 16 availability ofFor evidencebased peer guidelines review with effective treatmentsonly for improving 17 18 outcomes of AF.79 However, poor compliance with evidencebased therapies have 19 20 been reported in China, including assessment of thromboembolic risk, anticoagulation 21 22 therapy, heart rate control, rhythm control, and adequate treatment of concomitant 23 24 diseases.10,11 Several studies with diversified methodologies have reported that more 25 26 27 than 60% of patients with AF that eligible for anticoagulant treatment receive no risk 28 1013 29 stratification for stroke or therapy. 30 31

32 Although previous registries have expanded understanding of clinical practice of http://bmjopen.bmj.com/ 33 34 AF in China, they have been limited in the representativeness of hospitals and lack of 35 10,12,13 36 quality improvement components. To promote the use of guidelines of 37 38 recommended therapies and to assess the performance of quality improvement 39 40 efforts, the Chinese Society of Cardiology (CSC) and the American Heart on September 23, 2021 by guest. Protected copyright. 41 42 Association (AHA) initiated the Improving Care for Cardiovascular Disease in China 43 44 45 (CCC) project – AF program. The CCCAF is on the Get With The Guidelines

46 14 47 (GWTG) initiative of AHA. As a quality improvement initiative with timely 48 49 feedback for care of patients with AF, CCCAF will enhance the quality of care for 50 51 AF through furnishing specially designed tools for quality improvement. 52 53 54 This paper aims to present the objectives, organizational framework and 55 56 governance, hospital and patient enrollment, data collection, quality improvement 57 5 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 7 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 tools for AF care, and current progress of the CCCAF program. 4 5 6 METHODS 7 8 Study objectives 9 10 11 The CCCAF program aims to promote implementation of guidelinerecommended 12 13 therapies for AF patients using rapid cycle of data collection, analysis, feedback, and 14 15 process improvement. The objectives of the CCCAF program include understand the 16 For peer review only 17 18 current situation and main problems for management of AF inpatients , assess the 19 20 performance of the current strategy on quality improvement for AF management, as 21 22 well as explore and refine the optimal approach to improve clinical management of 23 24 AF. The timing and dynamic monitoring of AF management will provide an 25 26 opportunity to identify the potential needs of further evidence in management of AF. 27 28 Experience from this program may also help to guide development of the national 29 30 31 health quality improvement system and provide a blueprint for adaptation to other

32 http://bmjopen.bmj.com/ 33 regions of the world. 34 35 36 Organizational framework and governance 37 38 As a collaborative project of the CSC and the AHA , the CCCAF is conducted by the 39

40 on September 23, 2021 by guest. Protected copyright. Beijing Institute of Heart, Lung and Blood Vessel Diseases. AHA secured the initial 41 42 43 project funding and CSC provided hospital network for CCCAF. As a continuous 44 45 quality improvement program launched in February 2015, CCCAF has secured its 46 47 funding up to December 2018. This program consists of a senior management group 48 49 (SMG) and a project management group (Figure S1). Six senior clinician volunteers 50 51 from AHA (Prof. Smith, Prof. Fonarow and Prof. Taubert) and CSC (Prof. Huo, Prof. 52 53 Ge and Prof. Ma) in the SMG communicate frequently via teleconferences, emails 54 55 56 and facetoface meetings to ensure the scientific integrity and supervise the 57 6 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 8 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 implementation of the CCCAF program. Under the leadership of the international 4 5 and national directors (Ms. Morgan and Prof. Zhao), the project management group 6 7 oversees the operation of the CCCAF project. The project coordinator (Prof. Jing 8 9 Liu) supervises for functional groups, namely daily routine management (Ms. Jun Liu 10 11 and Ms. Zhou), data (Dr. Hao and Ms. Guo), and advisory and education groups. Data 12 13 14 collection and analysis are managed by daily routine management group and data 15 16 group, with guidanceFor frompeer SMG. Researchers review from SMG, only daily routine management 17 18 group and participating hospitals have the access to analysis the data for publications. 19 20 21 Hospital recruitment 22 23 15 24 Hospitals were recruited by geographiceconomic regions and the detailed hospital 25 26 sampling frame is shown in Supplemental Table 1. A total of 150 hospitals were 27 28 recruited, accounting for about 10% of the tertiary hospitals in China. Tertiary 29 30 hospitals in the CCC AF program meet following criteria: (1) the annual number of 31 32 patients hospitalized with AF was over 120; and (2) the director of the Cardiology http://bmjopen.bmj.com/ 33 34 Department agreed to join the program. Traditional Chinese medicine hospitals and 35 36 specialized hospitals without cardiology wards were not included in CCCAF 37 38 39 program. Supplemental Table 2 and Supplemental Table 3 provide the information of

40 on September 23, 2021 by guest. Protected copyright. 41 the 150 CCC AF hospitals recruited in phases one and two. 42 43 44 Patient recruitment 45 46 In each hospital, the first 1020 hospitalized patients with AF are enrolled in a 47 48 49 consecutive manner. Study inclusion of AF is based on electrocardiograph results, 50 51 which are recorded by 12lead electrocardiography (ECG), 24hour Holter ECG , or 52 53 other cardiac rhythm monitors. Patients with AF secondary to reversible condition 54 55 (e.g., untreated thyroid disease and pulmonary embolism) are excluded from the 56 57 7 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 9 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 study. 4 5 Clinical data elements are collected referring to American College of Cardiology 6 7 (ACC)/AHA recommendations on the data standards for clinical research of AF.16,17 8 9 As a quality improvement initiative, the CCCAF program has high priority for 10 11 collection of data elements that are involved in assessment for quality of care. 12 13 14 Moreover, additional data elements are gathered to facilitate indepth analysis. Data 15 16 elements includeFor patients’ peer demographics, review admission information, only medical history, in 17 18 hospital care and outcomes, and discharge medications for management of AF, as 19 20 presented in the case report form (Supplemental Table 4). Collection of personal 21 22 identifiers allows the potential for linking our dataset to other health records including 23 24 death and hospitalization data in the future. Eligible patients with AF are reported to 25 26 27 the database using Oracle Clinical Remote Data Capture system (Oracle Corporation). 28 29 Each participating center assigns a data abstractor responsible for data collection. The 30 31 data abstractor collects the clinical information from medical records and enter it into

32 http://bmjopen.bmj.com/ 33 the online data reporting system before middle of the month after discharge of the 34 35 patient. 36 37 38 Quality control of data collection 39

40 on September 23, 2021 by guest. Protected copyright. 18 41 Similar to the CCCAcute Coronary Syndrome (ACS) program, four approaches 42 43 are adopted to secure the accuracy and completeness of data in the CCCAF 44 45 program. (1) Facetoface training workshops are conducted prior to the data entry, 46 47 with interpretations for each data item. (2) The standardized online reporting tool 48 49 checks the data automatically for invalid values and sends the system generated error 50 51 52 messages to data abstractor for validation. (3) Onsite quality control from the third 53 54 party is performed to ensure the data accuracy. Recruited cases are compared with 55 56 the inpatient list to make sure that cases are reported in a consecutive manner, and 57 8 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 10 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 five percent of the records are chosen at random for comparison with the medical 4 5 charts. (4) Data completeness is calculated as number of data elements filled in the 6 7 database divided by number of data elements that should be filled. Each month, data 8 9 completeness is inspected and sent to participating sites as feedback in the monthly 10 11 reports. For hospitals with data completeness less than 90%, local investigators are 12 13 14 contacted to improve quality of data. 15 16 PerformanceFor measures peer review only 17 18 19 Primary and secondary performance measures are designed to evaluate the quality of 20 21 care for patients hospitalized with AF in the CCCAF program. They are constructed 22 23 1921 24 referring to the ACC/AHA statements on AF performance measures integrating 25 26 recommendations from the most updated ACC/AHA guideline and Chinese statement 27 7,22 28 for AF. The six primary performance measures are assessment of thromboembolic 29 30 risk, anticoagulant drug at discharge, prothrombin time (PT)/ international 31 32 normalized ratio (INR) planned followup, angiotensinconverting enzyme inhibitor http://bmjopen.bmj.com/ 33 34 (ACEI)/ angiotensin receptor blocker (ARB), statins and betablockers at discharge 35 36 in AF inpatients with indications (Table 1). The full measure specifications are 37 38 39 shown in Supplemental Table 5. Eight secondary performance measures are shown in

40 on September 23, 2021 by guest. Protected copyright. 41 Table 2 with their full measure specifications shown in Supplemental Table 6. For 42 43 each performance measure, specialized inclusion and exclusion criteria are utilized 44 45 and only appropriate tolerable patients with no contraindications are counted as 46 47 denominators. 48 49 50 The hospital composite scores of primary performance measure are constructed 51 52 using an opportunitybased method. These scores are defined as the total number of 53 54 treatments correctly given divided by the sum of eligible opportunity of treatments 55 56 57 9 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 11 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 23 3 among the six primary performance measures. Patients at a CCCAF hospital 4 5 contribute eligible opportunities for care to the composite performance scores of this 6 7 hospital. In the same way, the composite score for secondary performance measures is 8 9 constructed using the eight secondary performance measures. 10 11 12 The CCC team will update the performance measures and keep them aligned with 13 14 the new or updated clinical guidelines for management of AF when necessary. After 15 16 the new or updatedFor AF peerguidelines are review released, clinical expertsonly will evaluate whether 17 18 19 applying these changes in guidelines to CCCAF performance measures and data 20 21 elements associated with them in the case report form is necessary. When changes are 22 23 adopted in the performance measures, hospitals have a transition period that allows 24 25 them to have flexibility in meeting recognition criteria for the update. 26 27 28 Quality improvement tools 29 30 31 Several quality improvement tools are designed to promote the adherence to AF

32 http://bmjopen.bmj.com/ 33 guidelines including monthly hospital quality report, annual hospital recognition, 34 35 training session, as well as online educational materials. 36 37 38 Monthly hospital quality report 39

40 on September 23, 2021 by guest. Protected copyright. Each month, hospitals receive sitespecific feedback reports on quality of care for AF 41 42 43 through the CCC website. The content of hospital quality report includes individual 44 45 and composite scores for primary and secondary performance measures, as well as 46 47 data completeness of the reported AF cases. External and internal benchmarks are 48 49 provided and compared with the hospitalspecific data in the report. External 50 51 benchmarks are designed to present rational nation level of performance thresholds 52 53 and help to find out the areas for further enhancement of performance. The monthly 54 55 56 hospital quality report provides two external benchmarks: the nationlevel 57 10 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 12 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 benchmark and the attainable benchmark of performance describing the composite 4 5 performance of care delivered by the 15% hospitals with topperforming. Internal 6 7 benchmark presents the time trend of performance measures using hospital specific 8 9 data. These benchmarking quality reports help hospitals to identify areas for 10 11 improvement and refine treatment processes to ensure they are in line with the 12 13 14 guidelines. Frequencies of website visit and download are recorded to assess 15 16 involvementFor of these participatingpeer hospitals. review only 17 18 19 Regional workshop 20 21 Regional workshops in line with CSC meetings occur once or twice each year to 22 23 24 outline the project update, exchange experience, consult the obstacles confronted, 25 26 and share the most recent advances in therapies of AF. These facetoface meetings 27 28 serve as venues where the knowledge are shared, with discussion forums enabling 29 30 delegates to identify personal and local actions needed to improve clinical practice 31 32 for AF. Recourses for education of AF healthcare professionals, including handout, http://bmjopen.bmj.com/ 33 34 bulletin, pocket guideline and booklet are delivered to attendees. 35 36 37 Hospital recognition 38 39

40 Participating hospitals with best practice are awarded during the annual scientific on September 23, 2021 by guest. Protected copyright. 41 42 sessions of CSC. Six types of awards are issued each year, including gold, silver, and 43 44 bronze prizes for AF performance measures, and recognitions for active 45 46 participation, progress, and data quality. Recognition criteria are the same as those in 47 48 18 49 the CCCACS program. Hospitals with best practice share their processes behind 50 51 the achievement of good clinical practice for AF. 52 53 Online educational materials 54 55 56 The CCC website provides a variety of online educational materials in the education 57 11 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 13 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 source center for healthcare professionals in the participating hospitals to view and 4 5 download. These webbased training materials include updated clinical guidelines and 6 7 scientific statements for AF and webinars. Webinars are specially designed by clinical 8 9 experts, focusing on the areas with gaps between clinical practice and guideline 10 11 recommendations identified in the program. 12 13 14 Data management 15 16 For peer review only 17 Data reported by hospitals is reserved at the central office in solidly protected 18 19 computer systems. Data managers perform regular data cleaning inspecting for the 20 21 potential illogical and invalid values. Invalid values are defined as outliers in numeric 22 23 24 variables and unexpected values in character variables. Once the data manager detect 25 26 the illogical and invalid values, they will review the related observations and trace to 27 28 solve the potential errors. 29 30 31 Statistical considerations

32 http://bmjopen.bmj.com/ 33 Recruitment of 1500 patients (10 in each of the 150 hospitals) with AF per month will 34 35 36 detect an improvement in the primary composite score from 45% at baseline to an 37 38 expected score of 51%, with 91% power in a twosided test with a significant level of 39

40 0.05. The projected 6% improvement (from 45% to 51%) in primary composite score on September 23, 2021 by guest. Protected copyright. 41 42 means that more 6% guideline recommended treatments will be correctly given for 43 44 AF patients. Researchers from SMG, project management group and participating 45 46 hospitals have the access to analysis the data in a deidentified way, in both hospital 47 48 49 level and patient level. Categorical variables are presented as frequencies and 50 51 percentages and continuous variables are as means and standard deviations or 52 53 medians and interquartile ranges. Missing data are managed based on the purpose of 54 55 the study and analysis method used. The chisquare trend test is performed to evaluate 56 57 12 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 14 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 the temporal trend of performance measures. Univariate and multivariable analysis 4 5 are performed to recognize the element related with outcomes concerned, e.g. the 6 7 implement of specific treatments and inhospital events. To address intrahospital 8 9 correlation, generalized estimating equation models will be applied. All statistical 10 11 analyses are performed by SAS version 9.2 (SAS Institute, Inc., Cary, North 12 13 14 Carolina). Twosided P values < 0.05 are considered statistically significant. 15 16 Progress to Fordate peer review only 17 18 19 A total of 150 tertiary hospitals were recruited into the program in two phases, with 20 21 96 (64%) sites in municipalities or provincial capitals, and 54 (36%) in regional 22 23 24 cities. The locations of participating centers are displayed in Figure 1. A total of 28 25 26 801 AF inpatients were recruited from February 2015 to March 2017. The 27 28 demographic and clinical information of the overall population is presented in Table 29 30 3. The mean age of the population was 68.6 years and 15 738 (54.6%) were men. 31 32 These patients had high prevalence of the concomitant diseases, including http://bmjopen.bmj.com/ 33 34 hypertension (65.4%), coronary artery disease (31.4%), heart failure (20.1%) and 35 36 diabetes mellitus (17.9%). 37 38 39 The composite score for primary performance measures was 46.8% in the AF 40 on September 23, 2021 by guest. Protected copyright. 41 patients recruited (Figure 2). There were remarkable variations in composite scores 42 43 44 for AF across centers, ranging from 8.2% to 89.4%. The composite score of the AF 45 46 secondary performance measures for all hospitals was 51.4%, with a wide range of 47 48 1.8%–96.2% (Figure 3). Table 1 and Table 2 present the adherence rates to each of 49 50 the primary and secondary performance measures. Hospitalspecific AF monthly 51 52 quality reports between February 2015 and March 2017 are deposited on the website 53 54 (www.cccheart.com). 55 56 57 13 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 15 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Patient and public involvement 4 5 6 Public and patients have not been engaged in proposal of the research question, 7 8 design, recruitment and implement of the study. The results will be dispersed to study 9 10 participants by public reporting. 11 12 13 DISCUSSION 14 15 The growing population with AF and expanded awareness of AF related mortality, 16 For peer review only 17 morbidity and impaired quality of life lead to development of further therapies for AF. 18 19 Currently, there are several evidencebased, highly effective, guidelines of 20 21 recommended therapies that can significantly improve longterm care outcomes. The 22 23 24 ACC, AHA and European Society of Cardiology have compiled these treatments into 25 7,8 26 clinical practice guidelines. Although these guidelines are widely available, studies 27 28 have suggested that the compliance with guidelinerecommended treatments is low in 29 30 China, even among tertiary hospitals.10,11 Reasons for low compliance to guideline 31 32 based therapies include a lack of timely feedback, poor communication, and a lack of http://bmjopen.bmj.com/ 33 34 knowledge, financial resource, or time.24,25 35 36 37 Accordingly, multiple strategies for improving adherence for clinical guideline are 38 39 developed. Among them, three strategies are widely used, which are increasing 40 on September 23, 2021 by guest. Protected copyright. 41 reporting of the data, offering incentives to increase adherence for guideline, and 42 43 44 providing hospitals and healthcare professionals with framework and instruments 45 26 46 which are essential for adherence improvement. In 2008, the National Health and 47 48 Family Planning Commission of China (currently known as National Health 49 50 Commission) launched a project for quality management of single diseases for heart 51 52 failure, acute myocardial infarction and coronary artery bypass grafting. This project 53 54 aimed to enhance the reporting of these diseases and promote improvement in 55 56 57 14 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 16 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 27 3 quality. However, reporting without timely feedback and a lack of necessary 4 5 infrastructure for quality improvement prevented quality management of this single 6 7 diseases program from effective improvement in care. 8 9 10 Previous registry studies have provided information on clinical management of 11 12 patients with AF in China (Table 4) 10,12,13,2831 and worldwide.3135 Zhang et al 13 14 enrolled 2016 patients with AF in 20 hospitals from 2008 to 2011.10 Among patients 15 16 with nonvalvularFor AF, peeronly 12.7% of review those with a CHADS only2 score of ≥2 received 17 18 19 treatments with oral anticoagulants, which was much lower than that in developed 20 32,3639 21 countries reported by international registries. As an ongoing registry, the 22 23 Chinese Atrial Fibrillation Registry was launched in 2011 with an enrollment goal of 24 25 20,000 patients with AF in Beijing from 32 hospitals, with a followup of every six 26 27 months up to 2020.12 Although these registries have expanded understanding for 28 29 clinical practice and longterm outcomes of AF, they have been limited in a finite 30 31

32 number of hospitals and lack of quality improvement components. http://bmjopen.bmj.com/ 33 34 In 2014, the AHA and CSC launched the CCCAF program, aiming to promote 35 36 the quality of care for AF using timely feedback and quality improvement tools. The 37 38 18 39 CCCAF program is similar to the CCCACS program. This program will contribute

40 on September 23, 2021 by guest. Protected copyright. 41 essential nationwide information regarding characteristic, management and inhospital 42 43 outcomes of AF inpatients. It supports hospitals for improvement in use of guideline 44 45 recommended treatments with providing hospitalspecific monthly quality reports. 46 47 Targeted tools, including regional workshops and webinars, can further help to 48 49 narrow the gaps identified between clinical practice and guideline recommendations. 50 51 52 As an ongoing registry, the CCCAF program have the potential to track the 53 54 expansion of new evidencebased therapies and highlight the fields calling for 55 56 additional quality improvement efforts. 57 15 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 17 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 The CCCAF program aims to improve implement of guidelinerecommended 4 5 therapies for AF with multiple quality improvement tools. As shown in the improve 6 7 treatment with oral anticoagulants in atrial fibrillation (IMPACTAF) study, 8 9 educational intervention with integrative education increased the percentage of 10 11 patients receiving oral anticoagulant treatments and can potentially improve stroke 12 13 40 14 prevention for patients with AF. Currently, guidelinebased therapies for AF mainly 15 16 focus on antithromboticFor peer management, review rate and rhythm control, only and therapy of 17 18 concomitant cardiac diseases. For antithrombotic management, risk stratification is an 19 20 essential step for recognizing candidate patients for therapy and deciding which 21 22 patients have sufficient risk to warrant oral anticoagulation. Quality improvement 23 24 tools of the CCCAF program are designed to prompt assessment of thromboembolic 25 26 27 risk based on easily used risk stratification scores, as well as the use of anticoagulant 28 29 drugs at discharge, PT/INR planned followup, and therapy of concomitant cardiac 30 31 diseases using ACEIs/ARBs, betablockers, and statins at discharge in AF patients

32 http://bmjopen.bmj.com/ 33 with indications. Because AF patients are usually admitted with concomitant 34 35 cardiovascular diseases, careful consideration of coprescription of anticoagulant and 36 37 antiplatelet therapies is warranted, balancing the risk of stroke and bleeding. The 38 39

40 CCCAF program will provide important insight for patterns of current clinical on September 23, 2021 by guest. Protected copyright. 41 42 practice for patients with AF and concomitant cardiovascular diseases (e.g., ACS) and 43 44 procedures (e.g., percutaneous coronary intervention). 45 46 47 The CCCAF program has several strengths, including involvement of 48 49 international research team and nationwide network of tertiary hospitals. It helps to 50 51 translate the research findings into action of quality improvement for care of AF. In 52 53 China, tertiary hospitals deliver toplevel healthcare and affect clinical practice in 54 55 primary and secondary healthcare facilities. Quality improvement in these tertiary 56 57 16 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 18 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 hospitals will lead to spreading the experience to healthcare facilities of other levels 4 5 and promote the diffusion of guidelinerecommended therapies. Moreover, data 6 7 quality of our study is ensured by multiple strategies including training, standardized 8 9 data collection platform, onsite quality control and monitoring of data completeness. 10 11 12 There are several limitations of CCCAF program that should be mentioned. 13 14 Participation is voluntary and only tertiary hospitals are enrolled in this study. These 15 16 centers tend Forto be bigger peer hospitals possessing review more resources, only which may 17 18 19 overestimate the care quality. While participating centers are trained to report the 20 21 eligible AF patients consecutively, selection bias may exist as it is challenging to 22 23 identify all AF patients in an accurate and uniform manner. As clinical information are 24 25 abstracted from inpatient records, quality of documentation has potential impact on 26 27 the current study. Moreover, CCCAF program only collects information during 28 29 hospitalization, future work tracking patients after discharge will promote further 30 31

32 researches regarding effectiveness of specific treatments on longterm outcomes. http://bmjopen.bmj.com/ 33 34 Also, results presented here are preliminary and should be interpreted with caution. 35 36 As a nationwide quality improvement program, CCCAF aims to provide an 37 38 opportunity to improve implement of guidelinerecommended therapies in managing 39 40 AF. This program has diversified tools for quality improvement which could improve on September 23, 2021 by guest. Protected copyright. 41 42 patients’ outcomes. 43 44 45 Ethics and dissemination 46 47 48 This study has been approved by the by the Ethics Committee of Beijing Anzhen 49 50 Hospital, with the waiver of patient consent. One hundred and eleven hospitals 51 52 accepted central ethics approval and the other 39 sites applied IRB approval from 53 54 their own ethics committees. The protocol is listed on www.clinicaltrials.gov 55 56 57 17 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 19 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 (NCT02309398). Results will be published in peerreviewed medical journals. 4 5 6 Acknowledgments 7 8 We thank all the researchers from 150 participating centers. Names of the principal 9 10 11 investigators and participating centers are presented in Supplemental Table 2 and 12 13 Supplemental Table 3. 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 18 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 20 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 REFERENCES 4 5 6 1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for 7 8 stroke: the Framingham Study. Stroke. 1991;22:983988. 9 2. Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact 10 11 of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 12 13 1998;98(10):946952. 14 15 3. Hu D, Sun Y. Epidemiology, risk factors for stroke, and management of atrial 16 For peer review only 17 fibrillation in China. J Am Coll Cardiol. 2008;52:865868. 18 19 4. Zhou Z, Hu D, Chen J, Zhang R, Li K, Zhao X. An epidemiological survey of atrial 20 21 fibrillation in China. Chinese Journal of Internal Medicine. 2004;43:491494. 22 23 5. Li Y, Wu YF, Chen KP, et al. Prevalence of atrial fibrillation in China and its risk 24 25 factors. Biomed Environ Sci. 2013;26(9):709716. 26 27 6. Guo Y, Tian Y, Wang H, Si Q, Wang Y, Lip GY. Prevalence, incidence, and lifetime 28 29 risk of atrial fibrillation in China: new insights into the global burden of atrial 30 31 fibrillation. Chest. 2015;147(1):109119. 32 http://bmjopen.bmj.com/ 33 7. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the 34 35 management of patients with atrial fibrillation: executive summary: a report of the 36 37 American College of Cardiology/American Heart Association Task Force on practice 38 39 guidelines and the Heart Rhythm Society. Circulation. 2014;130:2071 2104. 40 on September 23, 2021 by guest. Protected copyright. 41 8. Camm AJ, Kirchhof P, Lip GY, et al. Guidelines for the management of atrial 42 43 fibrillation: the Task Force for the Management of Atrial Fibrillation of the European 44 45 Society of Cardiology (ESC). Europace. 2010;12(10):13601420. 46 47 9. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of 48 49 atrial fibrillation developed in collaboration with EACTS: The Task Force for the 50 51 management of atrial fibrillation of the European Society of Cardiology (ESC) 52 53 Developed with the special contribution of the European Heart Rhythm Association 54 55 (EHRA) of the ESC Endorsed by the European Stroke Organization (ESO). Eur 56 57 19 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 21 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Heart J. 2016; 37: 28932962 4 5 10. Zhang H, Yang Y, Zhu J, et al. Baseline characteristics and management of patients 6 7 with atrial fibrillation/flutter in the emergency department: results of a prospective, 8 9 multicentre registry in China. Intern Med J. 2014;44:742748. 10 11 11. Zhang S. Atrial fibrillation in mainland China: epidemiology and current 12 13 management. Heart. 2009;95:10521055. 14 15 12. Chang SS, Dong JZ, Ma CS, et al. Current Status and Time Trends of Oral 16 For peer review only 17 Anticoagulation Use Among Chinese Patients With Nonvalvular Atrial Fibrillation: 18 19 The Chinese Atrial Fibrillation Registry Study. Stroke. 2016; 47:18031810 20 21 13. Xiong Q, Shantsila A, Lane DA, et al. Sex differences in clinical characteristics and 22 23 inpatient outcomes among 2442 hospitalized Chinese patients with nonvalvular atrial 24 25 fibrillation: The Nanchang Atrial Fibrillation Project. Int J Cardiol. 2015;201:195 26 27 199. 28 29 14. Ellrodt AG, Fonarow GC, Schwamm LH, et al. Synthesizing lessons learned from get 30 with the guidelines: the value of diseasebased registries in improving quality and 31

40 on September 23, 2021 by guest. Protected copyright. definitions for measuring the clinical management and outcomes of patients with 41 42 atrial fibrillation: A report of the American College of Cardiology/American Heart 43 44 Association Task Force on clinical data standards (writing committee to develop data 45 46 standards on atrial fibrillation). Journal of the American College of Cardiology. 47 48 2004;44:475495. 49 50 17. Buxton AE, Calkins H, Callans DJ, et al. ACC/AHA/HRS 2006 key data elements 51 52 and definitions for electrophysiological studies and procedures: a report of the 53 54 American College of Cardiology/American Heart Association Task Force on Clinical 55 56 Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on 57 20 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 22 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Electrophysiology). J Am Coll Cardiol. 2006;48:23602396. 4 5 18. Hao Y, Liu J, Liu J, et al. Rationale and Design of the Improving Care for 6 7 Cardiovascular Disease in China (CCC) Project: a National Effort to Prompt Quality 8 9 Enhancement for Acute Coronary Syndrome. American Heart Journal. 2016 10 11 ;179:10715 12 13 19. Spertus JA, Eagle KA, Krumholz HM, Mitchell KR, Normand SL. American College 14 15 of Cardiology and American Heart Association methodology for the selection and 16 For peer review only 17 creation of performance measures for quantifying the quality of cardiovascular care. 18 19 Circulation. 2005;111:17031712. 20 21 20. Estes NA, 3rd, Halperin JL, Calkins H, et al. ACC/AHA/Physician Consortium 2008 22 23 clinical performance measures for adults with nonvalvular atrial fibrillation or atrial 24 25 flutter: a report of the American College of Cardiology/American Heart Association 26 27 Task Force on Performance Measures and the Physician Consortium for Performance 28 29 Improvement (Writing Committee to Develop Clinical Performance Measures for 30 Atrial Fibrillation): developed in collaboration with the Heart Rhythm Society. 31

40 on September 23, 2021 by guest. Protected copyright. on Performance Measures. Circulation. 2011;124:14831502. 41 42 22. Huang C, Zhang S, Huang D, et al. Current knowledge and management 43 44 recommendations of atrial fibrillation: 2015. Chinese Journal of Cardiac 45 46 Arrhythmias. 2015(5):321385. 47 48 23. Eapen ZJ, Fonarow GC, Dai D, et al. Comparison of composite measure 49 50 methodologies for rewarding quality of care: an analysis from the American Heart 51 52 Association's Get With The Guidelines program. Circ Cardiovasc Qual Outcomes. 53 54 2011;4:610618. 55 56 24. Cabana MD, Rand CS, Powe NR, et al. Why don't physicians follow clinical practice 57 21 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 23 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 guidelines? A framework for improvement. JAMA. 1999;282:14581465. 4 5 25. Berthiaume JT, Tyler PA, NgOsorio J, LaBresh KA. Aligning financial incentives 6 7 with "Get With The Guidelines" to improve cardiovascular care. Am J Manag Care. 8 9 2004;10:501504. 10 11 26. Lewis WR, Peterson ED, Cannon CP, et al. An organized approach to improvement 12 13 in guideline adherence for acute myocardial infarction: results with the Get With The 14 15 Guidelines quality improvement program. Arch Intern Med. 2008;168:18131819. 16 For peer review only 17 27. Chinese Hospital Association. Manual of single disease quality management. 18 19 Scientific and technical documentation press, Beijing, China. 2008. 20 21 28. Sun Y, Wang Y, Jiang J, Wang L, Hu D. Renal Dysfunction, CHADS2 Score, and 22 23 Adherence to the Anticoagulant Treatment in Nonvalvular Atrial Fibrillation: A 24 25 CrossSectional Study in Mainland China. Clin Appl Thromb Hemost. 2015. 26 27 29. Sun Y, Hu D, Li K, Zhou Z. Predictors of stroke risk in native Chinese with 28 29 nonrheumatic atrial fibrillation: retrospective investigation of hospitalized patients. 30 Clin Cardiol. 2009;32:7681. 31

40 on September 23, 2021 by guest. Protected copyright. 31. Huisman MV, Rothman KJ, Paquette M, et al. Antithrombotic Treatment Patterns in 41 42 Patients with Newly Diagnosed Nonvalvular Atrial Fibrillation: The GLORIAAF 43 44 Registry, Phase II. Am J Med. 2015;128:13061313 e1301. 45 46 32. Lip GY, Laroche C, Ioachim PM, et al. Prognosis and treatment of atrial fibrillation 47 48 patients by European cardiologists: one year followup of the EURObservational 49 50 Research ProgrammeAtrial Fibrillation General Registry Pilot Phase (EORPAF 51 52 Pilot registry). Eur Heart J. 2014;35:33653376. 53 54 33. Lewis WR, Piccini JP, Turakhia MP, et al. Get With The Guidelines AFIB: novel 55 56 quality improvement registry for hospitalized patients with atrial fibrillation. Circ 57 22 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 24 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Cardiovasc Qual Outcomes. 2014;7:770777. 4 5 34. Kakkar AK, Mueller I, Bassand JP, et al. International longitudinal registry of 6 7 patients with atrial fibrillation at risk of stroke: Global Anticoagulant Registry in the 8 9 FIELD (GARFIELD). Am Heart J. 2012;163):1319 e11. 10 11 35. Piccini JP, Fraulo ES, Ansell JE, et al. Outcomes registry for better informed 12 13 treatment of atrial fibrillation: Rationale and design of ORBITAF. American Heart 14 15 Journal. 2011;162:606612.e601. 16 For peer review only 17 36. Lamberts M, Gislason GH, Olesen JB, et al. Oral anticoagulation and antiplatelets in 18 19 atrial fibrillation patients after myocardial infarction and coronary intervention. J Am 20 21 Coll Cardiol. 2013;62:981989. 22 23 37. Piccini JP, Hernandez AF, Zhao X, et al. Quality of care for atrial fibrillation among 24 25 patients hospitalized for heart failure. J Am Coll Cardiol. 2009;54:12801289. 26 27 38. Steinberg BA, Kim S, Piccini JP, et al. Use and associated risks of concomitant 28 29 aspirin therapy with oral anticoagulation in patients with atrial fibrillation: insights 30 from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation 31

40 on September 23, 2021 by guest. Protected copyright. Heart J. 2011;32:22822289. 41 42 40. Vinereanu D, Lopes RD, Bahit MC, et al. A multifaceted intervention to improve 43 44 treatment with oral anticoagulants in atrial fibrillation (IMPACTAF): an 45 46 international, clusterrandomised trial. Lancet. 2017;390:17371746. 47 48 49 50 51 52 53 54 55 56 57 23 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 25 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Authors’ contributions: 4 5 6 The manuscript was prepared on behalf of the CCCAF Investigators. SS, Y Huo, GF, 7 8 JG, KT, CM and DZ conceived the study idea. Jing L, Jun L, LM, YG and MZ made 9 10 substantial contributions to the development of the study protocol. Y Hao drafted the 11 12 manuscript and all authors contributed to critical revisions of the paper. This final 13 14 manuscript was read and approved by all authors. 15 16 For peer review only 17 Funding 18 19 The CCC project is a collaborative program of the AHA and the CSC. The AHA was 20 21 funded by Pfizer for the quality improvement initiative through an independent grant 22 23 24 for learning and change. Pfizer provided no oversight on the goals, execution, or 25 26 publication of the program. The authors are solely responsible for the design and 27 28 conduct of this study, all study analyses, the drafting and editing of the manuscript, 29 30 and its final contents. 31 32 Disclosures http://bmjopen.bmj.com/ 33 34 The authors declare that they have no competing interests. 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 24 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 26 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Figure Legends 4 5 6 Figure 1. Distribution of hospitals for the CCCAF program. 7 8 Numerals on the map indicate the number of hospitals in the area. From Hao Y, Liu J, 9 10 11 Liu J, et al: Rationale and Design of the Improving Care for Cardiovascular Disease in 12 13 China (CCC) Project: a National Effort to Prompt Quality Enhancement for Acute 14 15 Coronary Syndrome. American Heart Journal. 2016 ;179:10715. 16 For peer review only 17 18 19 Figure 2. Distribution of CCCAF composite scores of primary performance measures 20 21 across hospitals from February 2015 to March 2017. 22 23 24 The composite scores were calculated based on the 6 primary performance measures, 25 26 using the sum of total instances when a required measure was performed (correct care 27 28 provided) divided by the total number of eligible opportunities. 29 30 31 32 Figure 3. Distribution of CCCAF composite scores of secondary performance http://bmjopen.bmj.com/ 33 34 measures across hospitals from February 2015 to March 2017. 35 36 The composite scores were calculated based on 8 secondary performance measures, 37 38 39 using the sum of total instances when a required measure was performed (correct care

40 on September 23, 2021 by guest. Protected copyright. 41 provided) divided by the total number of eligible opportunities. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 25 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from

8857) 3382) / / denominator) denominator)

(1794

1 Proportion,% Proportion,% 57.0 (1245/2184) 57.0 (1245/2184) 87.2 87.2 (7721 53. 61.2 (8524/13925) 61.2 (8524/13925) 46.8 (31081/66362) 46.8 (31081/66362) 42.3 (6413/15150) 23.6 (5384/22864) (Numerator/

discharge

up up planned

BMJ Open http://bmjopen.bmj.com/ VASc≥2. 2 DS 2 Title of Performance Measure Measure Title of Performance on September 23, 2021 by guest. Protected copyright. Composite scores of primary performance measures performance primary ofmeasures scores Composite For peer review only For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Proportion of AF patients with indications receiving ACEI/ARB at discharge at ACEI/ARB indications receiving AF with patients of Proportion Proportion of AF patients with indication prescribed a statin at discharge at discharge statin a prescribed indication AF with patients of Proportion Proportion of AF patients with indication prescribed an anticoagulant drug at discharge at discharge drug an anticoagulant prescribed indication AF with patients of Proportion discharge blocker at a beta prescribed indication AF with patients of Proportion a follow PT/INR who have on warfarin of Proportion discharged patients b c d

7 7, 22 7, 22 7, 22 7, 22 7, 22 7, 22 risk thromboembolic assessment inof AF whom nonvalvular of Proportion with patients Reference Reference indications refer to nonvalvular AF patients patients with CHA AF to indications nonvalvular refer angiotensin receptor blocker. angiotensin blocker. receptor AF, atrial fibrillation; PT, prothrombin time; INR, international normalized ratio; ACEI, angiotensinconverting enzyme inhibitor; ARB, ARB, inhibitor; enzyme angiotensinconverting ACEI, ratio; normalized international time; INR, prothrombin PT, fibrillation; atrial AF,

a Table 1. Primary Performance Measures for the CCCAF Project Project the CCCAF for Measures Primary Performance Table 1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 27 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from Page 28 of 74 27 27 BMJ Open http://bmjopen.bmj.com/ on September 23, 2021 by guest. Protected copyright.

For peer review only For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml indications refer to AF patients with acute myocardial infarction; or coronary heart disease with comorbidity of hypertension, diabetes mellitus mellitus diabetes of hypertension, with comorbidity heart disease or coronary infarction; myocardial with patients acute AF to indications refer or diabetes disease peripheral vascular attack, ischemic stroke/transient ischemic disease, heart with patients coronary AF to indications refer indications refer to AF patients with heart failure. failure. with patients heart AF to indications refer

b c d or chronic kidney disease; or left ventricular ejection fraction <40% according to the case records. case torecords. the according <40% fraction ejection ventricular or left disease; or chronic kidney mellitus. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from

12243) 5623) 10989) / / / denominator) denominator)

(1263 (7140 (10941 5 5 0 0 Proportion,% Proportion,% 4 4 72.2 (888/1230) 72.2 (888/1230) 22. 52.4 (2010/3838) 52.4 (2010/3838) 15.0 (3422/22864) 15.0 (3422/22864) 19.2 (4397/22864) 19.2 (4397/22864) 65. 88.3 (25547/28615) 88.3 (25547/28615) 89. 51.4 51.4 (55608/108266) (Numerator/

VASc score reported reported score VASc score reported reported score 2 2 DS 2 28 28

BMJ Open http://bmjopen.bmj.com/ Title of Performance Measure Measure Title of Performance performance measures performance

on September 23, 2021 by guest. Protected copyright. secondary For peer review only For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Proportion of AF patients with indication prescribed aldosterone antagonist at discharge at discharge antagonist prescribed aldosterone indication AF with patients Proportion of

Proportion of AF patients who have a documented resting heart rate of <80 bpm closest bpm closest to discharge of heart resting rate <80 documented a have AF patients who ofProportion anticoagulation education therapy receiving AF patients that ofProportion a counseling or cessation advice smoking are AF patients given who ofProportion of Composite scores

20 20 22 22 CHADS a who had AF patients of Proportion nonvalvular 7, 22 7, 22 at discharge warfarin patients prescribed AF valvular Proportion 7, 22 7, 22 7, 22 7, 22 CHA a who had AF patients of Proportion nonvalvular 7, 22 education conventional medical receiving AF patients that of Proportion Reference Reference indications refer to acute myocardial infarction patients with left ventricular ejection fraction (LVEF)<40% or heart failure or diabetes mellitus; failure mellitus; or diabetes or heart (LVEF)<40% fraction ejection ventricular left with patients infarction myocardial acute to indications refer

AF, atrial fibrillation. fibrillation. atrial AF, a or the heart failure patients patients failure with LVEF<35%. or the heart

Table 2. Secondary Performance Measures for the CCCAF CCCAF Project for the Measures Performance Table Secondary 2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 29 of 74 BMJ Open Page 30 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Table 3. Characteristics of Enrolled Patients with AF enrolled from February 2015 to 4 5 March 2017 6 7 8 Men Women Overall 9 10 n=15738 n=13063 n=28801 11 12 13 Age 14 15 mean (SD), y 67.0(12.7) 70.6(11.2) 68.6 (12.1) 16 For peer review only 17 Age group, n (%) 18 19 <65 y 6528(41.5) 3823(29.3) 10351(35.9) 20 21 22 6574 y 4512(28.7) 4079(31.2) 8591(29.8) 23 24 ≥75 y 4698(29.9) 5161(39.5) 9859(34.2) 25 26 Healthcare insurance, n (%) 27 28 Urban employeesbasic insurance 6823(43.4) 5045(38.6) 11868(41.2) 29 30 Urban residentsbasic insurance 2817(17.9) 2782(21.3) 5599(19.4) 31 32 New rural cooperative insurance 2696(17.1) 2830(21.7) 5526(19.2) http://bmjopen.bmj.com/ 33 34 Selfpaying 1654(10.5) 1186(9.1) 2840(9.9) 35 36 37 Others 1748(11.1) 1220(9.3) 2968(10.3) 38 39 Medical history, n (%)

40 on September 23, 2021 by guest. Protected copyright. 41 Hypertension 9973(63.4) 8874(67.9) 18847(65.4) 42 43 CAD 5050(32.1) 3991(30.6) 9041(31.4) 44 45 Heart failure 2994(19.0) 2788(21.3) 5782(20.1) 46 47 Diabetes mellitus 2694(17.1) 2473(18.9) 5167(17.9) 48 49 50 Stroke/TIA 2187(13.9) 1843(14.1) 4030(14) 51 52 PAD 1647(10.5) 915(7.0) 2562(8.9) 53 54 Myocardial infarction 1191(7.6) 551(4.2) 1742(6.0) 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 31 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 Previous bleeding 96(0.6) 74(0.6) 170(0.6) 4 5 Current smoker 5241(33.3) 413(3.2) 5654(19.6) 6 7 AF type 8 9 Newly diagnosed 1742(11.1) 1330(10.2) 3072(10.7) 10 11 12 Paroxysmal 6143(39.0) 5053(38.7) 11196(38.9) 13 14 Persistent 4256(27.0) 3405(26.1) 7661(26.6) 15 16 PermanentFor peer review2447(15.5) only 2327(17.8) 4774(16.6) 17 18 Unknown 1150(7.3) 948(7.3) 2098(7.3) 19 20 21 AF, atrial fibrillation; SD, standard deviation; CVD, cardiovascular disease; CAD, 22 23 coronary artery disease; PCI, percutaneous coronary intervention; TIA, transient 24 25 ischemic attack; PAD, peripheral artery disease. 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

2013 present

2011 2011

No 2 2 year Follow up up Follow Study period

QI QI No No measure measure

size size 2442 2016 2016 No 1 year 20082011 10871 Sample Sample

31 31 BMJ Open http://bmjopen.bmj.com/ Inpatient Outpatient

1 736 on September 23, 2021 by guest. Protected copyright.

42 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

For peer China only review only

China only 20 department Emergency 13 China only 50 Outpatient 3017 No No 2012 10 30 858 Outpatient/inpatient 17184 No 1 year 20102013

28 30 31 China only 18 Inpatient 3425 No No 20002004 29 China only 32 Outpatient/inpatient 11496 No Up 2020 to present 2011 12 AF AF II Studies Studies Countries Sites Population CAFR Sun al. et Sun GLORIA GARFIELDAF GARFIELDAF Sun Y et al. etal. 2015 Y Sun Chinese AF registry AF registry Chinese Nanchang AF AF Project Nanchang CAFR, Chinese Atrial Fibrillation Registry Study; GLORIAAF, Global Registry on Longterm Oral Antithrombotic Treatment in Patients in Patients with Treatment Antithrombotic on Oral Longterm GlobalRegistry Study; GLORIAAF, Registry Fibrillation Atrial Chinese CAFR, Table 4. Characteristics of AF Registries Involving China Sites in Involving AF Registries of Characteristics Table 4.

Atrial Fibrillation; GARFIELDAF, Global Anticoagulant Registry in the FIELDAtrial Fibrillation; QI, quality improvement. improvement. quality QI, Fibrillation; FIELDAtrial in the Registry Anticoagulant Global GARFIELDAF, Fibrillation; Atrial 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 33 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Figure 1. Distribution of hospitals for the CCC-AF program. 32 Numerals on the map indicate the number of hospitals in the area. Adapted from reference 18. http://bmjopen.bmj.com/ 33 34 102x76mm (300 x 300 DPI) 35 36 37 38 39

40 on September 23, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 34 of 74 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 Figure 2. Distribution of CCC-AF composite scores of primary performance measures across hospitals from 38 February 2015 to March 2017. 39 The composite scores were calculated based on the 6 primary performance measures, using the sum of total

40 instances when a required measure was performed (correct care provided) divided by the total number of on September 23, 2021 by guest. Protected copyright. 41 eligible opportunities.

42 554x521mm (300 x 300 DPI) 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 35 of 74 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39 Figure 3. Distribution of CCC-AF composite scores of secondary performance measures across hospitals from on September 23, 2021 by guest. Protected copyright. 40 February 2015 to March 2017. 41 The composite scores were calculated based on 8 secondary performance measures, using the sum of total 42 instances when a required measure was performed (correct care provided) divided by the total number of 43 eligible opportunities. 44 45 536x543mm (300 x 300 DPI) 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 36 of 74

1 2 3

4 SUPPLEMENTAL MATERIAL BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 6 7 8 9 Contents 10 11 12 Supplemental Tables 13 14 15 Table S1. Hospital Sampling Frame of CCC-AF ...... 2 16 17 Table S2. List of Hospitals for Phase One ...... 3 18 For peer review only 19 20 Table S3. List of Hospitals for Phase Two ...... 7 21 22 Table S4. Case Report Form of CCC-AF ...... 11 23 24 25 Table S5. Definition of Primary Performance Measures ...... 18 26 27 Table S6. Definition of Secondary Performance Measures...... 29 28 29 30 31 32 Supplemental Figures 33 34 Figure S1. Organizational Framework and Governance of the CCC-AF Program ...... 40 35

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 23, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 37 of 74 BMJ Open

1 2 3 Table S1. Hospital Sampling Frame of CCC-AF

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 6 No. of Enrolled Enrolled GDP per No. of hospitals 7 & Territories * Provinces hospitals in hospitals hospitals 8 capital # needed（10%） the area in Phase 1 in Phase 2 9 10 Low NA ------11 Medium-low Shanxi 49 5 4 1 12 Northern Medium-high Hebei 55 5 4 2 13 China 14 Beijing, Tianjin, Inner High 123 12 13 1 15 Mongolia 16 Low NA ------17 18 Northeast Medium-lowFor peerHeilongjiang review77 only7 1 5 19 China Medium-high Jilin 39 4 2 1 20 High Liaoning 101 10 2 9 21 22 Low Anhui, Jiangxi 84 8 3 5 23 Medium-low NA ------24 Eastern Medium-high Fujian, Shandong 129 12 1 12 25 China 26 Shanghai, Jiangsu, High 240 23 13 11 27 Zhejiang 28 29 Low NA ------30 Central Medium-low Henan, Hunan 134 13 7 7 31 China Medium-high Hubei 60 6 0 5 32 33 High NA ------34 Low Guangxi 50 5 2 2 35 Southern Medium-low Hainan 11 1 2 0 36 http://bmjopen.bmj.com/ 37 China Medium-high NA ------38 High Guangdong 105 10 5 4 39 40 Low Guizhou, Yunnan, Tibet 82 8 3 2 Southwest 41 Medium-low Sichuan 83 8 0 5 42 China Medium-high Chongqing 22 2 3 0 43

44 High NA ------on September 23, 2021 by guest. Protected copyright. 45 Low Gansu 34 3 2 0 46 Western Medium-low Qinghai, Xinjiang 29 3 5 0 47 China 48 Medium-high Shaanxi, Ningxia 51 5 3 3 49 High NA ------50 51 Total 1558 150 75 75 52 &Mainland China includes seven geographical regions: Northern, Northeast, Eastern, Central, Southern, 53 54 Southwest, and Western China. *GDP per capital is from National Bauru of Statistical, provinces are 55 56 grouped into quadruplets according to GDP per capital, low:<29608.00 RMB, medium-low: 57 29608.00-36393.00 RMB, medium-high: 36394.00-54095.00 RMB, high: >54095.00 RMB. 58 59 60 #Numbers of hospitals are from China Statistical Yearbook 2013. 2

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 38 of 74

1 2 3

4 Table S2. List of Hospitals for Phase One BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 6 Hospitals Territories Provinces City Investigator 7 8 Northern Shanxi Cardiovascular Hospital Shanxi Taiyuan Bao Li 9 China 10 11 Nanjing Drum Tower Hospital, The Biao Xu, 12 Affiliated Hospital of Nanjing Eastern China Jiangsu Nanjing Guangshu 13 University Medical School Han 14 Southern 15 Hainan General Hospital Hainan Haikou Bin Li 16 China 17 The Second Hospital of Jilin Northeast 18 For peer reviewJilin onlyChangchun Bin Liu 19 University China 20 The 2nd Affiliated Hospital of Northeast Heilongjiang Harbin Bo Yu 21 Harbin Medical University China 22 The Ninth Hospital Affiliated to 23 Changqian 24 Shanghai Jiaotong University Eastern China Shanghai Shanghai Wang 25 School of Medicine 26 Chuanyu 27 Henan Provincial People's Hospital Central China Henan Zhengzhou 28 Gao 29 Northern 30 Shanxi Provincial People's Hospital Shanxi Taiyuan Chunlin Lai China 31 32 Xinqiao Hospital, Third Military Southwest Cui Bin, Lan Chongqing Chongqing 33 Medical University China Huang 34 Northern 35 China Meitan General Hospital Beijing Beijing Di Wu

36 China http://bmjopen.bmj.com/ 37 Fakuan The 309th Hospital of Chinese Northern 38 Beijing Beijing Tang, Jun 39 People's Liberation Army China 40 Xiao 41 Zhongda Hospital, Southeast Eastern China Jiangsu Nanjing Genshan Ma 42 University 43

The First Affiliated Hospital of Northeast on September 23, 2021 by guest. Protected copyright. 44 Liaoning Jinzhou Guizhou Tao 45 Liaoning Medical University China 46 Xinjiang Uygur Autonomous Northwest 47 Xinjiang Urumchi Guoqing Li 48 Region People’s Hospital China 49 Sir Run Run Shaw Hospital, Guosheng 50 College of Medicine, Zhejiang Eastern China Zhejiang Hangzhou 51 Fu 52 University 53 Beijing Friendship Hospital, Capital Northern Beijing Beijing Hongwei Li 54 Medical University China 55 The First Affiliated Hospital of Honhju 56 Eastern China Anhui Bengbu 57 Bengbu Medical College Wang 58 Northern Huifeng 59 General Hospital of TISCO Shanxi Taiyuan China Wang 60 3

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 39 of 74 BMJ Open

1 2 3 Hospitals Territories Provinces City Investigator 4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Southern 6 Dongguan People's Hospital Guangdong Dongguan Jianfeng Ye 7 China 8 Panyu Hospital of Chinese Southern 9 Guangdong Guangzhou Jianhao Li 10 Medicine China 11 Northern Peking University First Hospital Beijing Beijing Jie Jiang 12 China 13 Sun Yat-sen Memorial Hospital, Southern Jingfeng 14 Guangdong Guangzhou 15 Sun Yat-sen University China Wang 16 Southern 17 Guangdong General Hospital Guangdong Guangzhou Jiyan Chen China 18 For peer review only 19 Hospital of Xinjiang Production & Northwest Xinjiang Urumchi Junming Liu 20 Construction Corps China 21 The Military General Hospital of Northern 22 Beijing Beijing Junxia Li 23 Beijing PLA China 24 The First Affiliated Hospital of Southern 25 Guangxi Nanning Lang Li Guangxi Medical University China 26 27 Tongren Hospital Affiliated to 28 Shanghai Jiaotong University Eastern China Shanghai Shanghai Li Jiang 29 School of Medicine 30 31 Binzou City Center Hospital Eastern China Shandong Binzhou Lijun Meng 32 The First Affiliated Hospital of 33 Central China Henan Zhengzhou Ling Li 34 Zhengzhou University 35 Northwest Xijing Hospital Shaanxi Xi'an Ling Tao 36 China http://bmjopen.bmj.com/ 37 The Affiliated Hospital of Guizhou Southwest 38 Guizhou Guiyang Lirong Wu 39 Medical University China 40 First Affiliated Hospital of the 41 Northern People's Liberation Army General Beijing Beijing Miao Tian 42 China 43 Hospital

44 The Second People's Hospital of Southwest Minghua on September 23, 2021 by guest. Protected copyright. 45 Yunnan Kunming 46 Yunnan Province China Han 47 Southern Moshui Haikou People's Hospital Hainan Haikou 48 China Chen 49 Northwest 50 Gansu Provincial Hospital Gansu Lanzhou Ping Xie 51 China 52 The First Affiliated Hospital of 53 Pingshuan Henan University of Science and Central China Henan Luoyang 54 Dong 55 Technology 56 Qiaoqing 57 Chenzhou First People's Hospital Central China Hunan Chenzhou Zhong 58 59 People’s Hospital of Qinghai Northwest Qinghai Xining Rong Chang 60 Province China 4

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 40 of 74

1 2 3 Hospitals Territories Provinces City Investigator 4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Affiliated Hospital of Ningxia Northwest 6 Ningxia Yinchuan Shaobin Jia 7 Medical University China 8 Shaoping Beijing Anzhen Hospital, Capital Northern 9 Beijing Beijing Nie, Xiaohui 10 Medical University China 11 Liu 12 North Jiangsu People's Hospital Eastern China Jiangsu Yangzhou Shenghu He 13 14 Shanghai Sixth People's Hospital Eastern China Shanghai Shanghai Shixin Ma 15 16 Northern 17 The First Hospital of Handan Hebei Handan Shuanli Xin 18 For peerChina review only 19 Huai'an First People's Hospital Eastern China Jiangsu Huai'an Shuren Ma 20 21 The First Affiliated Hospital of Southwest Chongqing Chongqing Suxin Luo 22 Chongqing Medical University China 23 Northern 24 Navy General Hospital Beijing Beijing Tianchang Li 25 China 26 Zhejiang Provincial Hospital of 27 Eastern China Zhejiang Hangzhou Wei Mao 28 TCM 29 The Third Xiangya Hospital of Weihong Central China Hunan Changsha 30 Central South University Jiang 31 Affiliated Hospital of Qinghai Northwest 32 Qinghai Xining Weijun Liu 33 University China 34 Teda International Cardiovascular Northern 35 Tianjin Tianjin Wenhua Lin Hospital China 36 http://bmjopen.bmj.com/ 37 The Second Hospital of Hebei Northern Hebei Shijiazhuang Xianghua Fu 38 Medical University China 39 Xianxian 40 Changhai Hospital of Shanghai Eastern China Shanghai Shanghai 41 Zhao 42 The Second Affiliated Hospital to Xiaoshu 43 Eastern China Jiangxi Nanchang Nanchang University Cheng 44 on September 23, 2021 by guest. Protected copyright. 45 Northern Hebei General Hospital Hebei Shijiazhuang Xiaoyong Qi 46 China 47 Northern Inner Xingsheng 48 Inner Mongolia People's Hospital Hohhot 49 China Mongolia Zhao 50 The General Hospital of Shenyang Northeast 51 Liaoning Shenyang Yaling Han 52 Military Region China 53 The First Hospital of Jilin Northeast Jilin Changchun Yang Zheng 54 University China 55 Northern 56 Tianjin Chest Hospital Tianjin Tianjin Yin Liu 57 China 58 Hunan Provincial People's Hospital Central China Hunan Changsha Ying Guo 59 60 5

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 41 of 74 BMJ Open

1 2 3 Hospitals Territories Provinces City Investigator 4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Southwest 6 People's Hospital of Yuxi City Yunnan Yuxi Yinglu Hao 7 China 8 The People's Hospital of Guangxi Southern Yingzhong 9 Guangxi Nanning Zhuang Autonomous Region China Lin 10 11 The First Teaching Hospital of Northwest Xinjiang Urumchi Yitong Ma 12 Xinjiang Medical University China 13 Northern Inner 14 Baogang Hospital Baotou Yongdong Li 15 China Mongolia 16 Tianjin Medical University General Northern 17 Tianjin Tianjin Yuemin Sun 18 Hospital For peerChina review only 19 The Second Affiliated Hospital of Central China Henan Zhengzhou Yulan Zhao 20 Zhengzhou University 21 22 Nanfang Hospital of Southern Southern Guangdong Guangzhou Yuqing Hou 23 Medical University China 24 The First Affiliated Hospital to 25 Eastern China Jiangxi Nanchang Zeqi Zheng 26 Nanchang University 27 The First Affiliated Hospital of Northwest Zheng 28 Gansu Lanzhou 29 Lanzhou University China Zhang 30 Northern The Third Hospital of Shijiazhuang Hebei Shijiazhuang Zhenguo Ji 31 China 32 33 Wuxi People's Hospital Eastern China Jiangsu Wuxi Zhenyu Yang 34 35

36 Jiangsu Province Hospital Eastern China Jiangsu Nanjing Zhijian Yang http://bmjopen.bmj.com/ 37 38 The Second Hospital of Shanxi Northern Zhiming 39 Shanxi Taiyuan Medical University China Yang 40 41 The Affiliated Hospital of Xuzhou Zhirong Eastern China Jiangsu Xuzhou 42 Medical College Wang 43 Southwest Hospital, Third Military Southwest Zhiyuan 44 Chongqing Chongqing on September 23, 2021 by guest. Protected copyright. 45 Medical University China Song 46 The First Affiliated Hospital of Northwest 47 Shaanxi Xi'an Zuyi Yuan 48 Xi’an Jiaotong University China 49 50 51 52 53 54 55 56 57 58 59 60 6

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 42 of 74

1 2 3

4 Table S3. List of Hospitals for Phase Two BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 6 Hospitals Territories Provinces City Investigator 7 8 Yangzhou First People's Hospital Eastern China Jiangsu Yangzhou Aihua Li 9 10 Hospital 463 of Chinese People's Northeast Liaoning Shenyang Bosong Yang 11 Liberation Army China 12 Northwest 13 The Central Hospital of Mianyang Sichuan Mianyang Caidong Luo 14 China 15 Chunyan Liaocheng People's Hospital Eastern China Shandong Liaocheng 16 Zhang 17 Chunyang 18 Yancheng Third People'sFor Ho spitalpeer Eastern review China Jiangsu only Yancheng 19 Wu 20 The Second Xiangya Hospital of Daoquan 21 Central China Hunan Changsha 22 Central South University Peng 23 Northwest The Central Hospital of Panzhihua Sichuan Panzhihua Dawen Xu 24 China 25 Northeast 26 The First Hospital of Qiqihaer City Heilongjiang Qiqihaer Gang Xu 27 China 28 The Third the People‘s Hospital of Gengsheng 29 Eastern China Anhui Bengbu 30 Bengbu Sang 31 Northeast The First Hospital of Jiamusi Heilongjiang Jiamusi Guixia Zhang 32 China 33 Guoxiong 34 Zhoushan People's Hospital Eastern China Zhejiang Zhoushan 35 Chen

36 Northeast http://bmjopen.bmj.com/ 37 Dalian Municipal Central Hospital Liaoning Dalian Hailong Lin 38 China 39 Renmin Hospital of Wuhan Central China Hubei Wuhan Hong Jiang 40 University 41 Northwest 42 Ningxia People's Hospital Ningxia Yinchuan Hong Luan 43 China

44 The First People's Hospital of on September 23, 2021 by guest. Protected copyright. 45 Northwest Yunnan Province (Kunhua Yunnan Kunming Hong Zhang 46 China 47 Hospital) 48 The Central Hospital of Zhoukou Central China Henan Zhoukou Hualing Liu 49 50 Anyang District Hospital Central China Henan Anyang Hui Liu 51 Sichuan Provincial People’s Northwest 52 Sichuan Chengdu Jianhong Tao 53 Hospital China 54 Mudanjiang Cardiovascular Northeast Heilongjiang Mudanjiang Jianwen Liu 55 Disease Hospital China 56 57 Yichang Central Hospital Central China Hubei Yichang Jiawang Ding 58 59 60 Qilu Hospital of Shandong Eastern China Shandong Jinan Jifu Li 7

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 43 of 74 BMJ Open

1 2 3 Hospitals Territories Provinces City Investigator 4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 University 6 7 Affiliated Hospital of Jiangsu Eastern China Jiangsu Zhenjiang Jinchuan Yan 8 University 9 The First People's Hospital of Southern 10 Guangxi Nanning Jinru Wei 11 Nanning City China 12 The First Affiliated Hospital of Eastern China Fujian Fuzhou Jinzi Su 13 Fujian Medical University 14 Northwest 15 Chengdu Third People’s Hospital Sichuan Chengdu Jiong Tang 16 China 17 18 Yantaishan hospitalFor peerEastern review China Shandong only Yantai Juexin Fan 19 Qingdao Municipal Hospital Eastern China Shandong Qingdao Jun Guan 20 Zhongshan Hospital Affiliated to 21 Eastern China Shanghai Shanghai Junbo Ge 22 Fudan University 23 Kaihong Longyan First Hospital Eastern China Fujian Longyan 24 Chen 25 Affiliated Hospital of Guangdong Southern 26 Guangdong Guangzhou Keng Wu 27 Medical College China 28 29 Jiangxi Provincial People's Hospital Eastern China Jiangxi Nanchang Lang Ji 30 Anhui Provincial Hospital Eastern China Anhui Hefei Likun Ma 31 32 33 Xiangtan City Central Hospital Central China Hunan Xiangtan Lilong Tang 34 Northeast 35 The First Hospital of Haerbin City Heilongjiang Harbin Lin Wei

36 China http://bmjopen.bmj.com/ 37 Man Zhang, 38 Central Hospital Affiliated to Northeast Liaoning Shenyang Kaiming 39 Shenyang Medical College China 40 Chen 41 Manhua 42 The Central Hospital of Wuhan Central China Hubei Wuhan 43 Chen

44 Hangzhou First People's Hospital Eastern China Zhejiang Hangzhou Ningfu Wang on September 23, 2021 by guest. Protected copyright. 45 Peiying 46 The Central Hospital of Xuzhou Eastern China Jiangsu Xuzhou 47 Zhang 48 The Second hospital of Dalian Northeast 49 Liaoning Dalian Peng Qu 50 Medical University China 51 The First Affiliated Hospital of Northeast 52 Liaoning University of Traditional Liaoning Shenyang Ping Hou 53 China 54 Chinese Medicine 55 Beijing Tsinghua Changgung Northern Beijing Beijing Ping Zhang 56 Hospital China 57 Guizhou Provincial People's Northwest 58 Guizhou Guiyang Qiang Wu 59 Hospital China 60 8

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 44 of 74

1 2 3 Hospitals Territories Provinces City Investigator 4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 The First Affiliated Hospital of 6 Eastern China Fujian Xiamen Qiang Xie 7 Xiamen University 8 9 Quanzhou First Hospital Eastern China Fujian Quanzhou Rong Lin 10 11 Southern Wuzhou People's Hospital Guangxi Wuzhou Shaowu Ye 12 China 13 Northeast 14 The Central Hospital of Jilin Jilin Changchun Shuangbin Li 15 China 16 Xiangya Hospital Central South 17 Central China Hunan Changsha Tianlun Yang University 18 For peer review only 19 Southern Guangzhou Red Cross Hospital Guangdong Guangzhou Tongguo Wu 20 China 21 The First Affiliated Hospital of Southern 22 Guangdong Guangzhou Wei Wang 23 Guangzhou Medical College China 24 The First Affiliated Hospital of Weijian 25 Eastern China Zhejiang Wenzhou Wenzhou Medical University Huang 26 27 The Second Affiliated Hospital of Eastern China Jiangsu Suzhou Weiting Xu 28 Soochow University 29 30 Wuhan Asia Heart Hospital Central China Hubei Wuhan Xi Su 31 32 The First Affiliated Hospital of Xiangjun 33 Eastern China Jiangsu Suzhou 34 Soochow University Yang 35 Affiliated Hospital of Yan'an Northwest Xiaochuan Shaanxi Yan'an 36 University China Ma http://bmjopen.bmj.com/ 37 The First People's Hospital of 38 Eastern China Shandong Jining Xiaofei Sun 39 Jining 40 Northern Xiaoping 41 The Central Hospital of Taiyuan Shanxi Taiyuan 42 China Chen 43 West China Hospital of Sichuan Northwest Xiaoping Sichuan Chengdu 44 University China Chen on September 23, 2021 by guest. Protected copyright. 45 The Third Affiliated Hospital of Southern 46 Guangdong Guangzhou Ximing Chen 47 Guangzhou Medical College China 48 The First Affiliated Hospital of Xingsheng 49 Eastern China Anhui Wuhu Wannan Medical College Tang 50 51 Tangdu Hospital of The Fourth Northwest Shaanxi Xi'an Xue Li 52 Military Medical University China 53 Shanghai East Hospital Affiliated 54 Eastern China Shanghai Shanghai Xuebo Liu 55 to Tongji University 56 Xiamen Cardiovascular Disease 57 Eastern China Fujian Xiamen Yan Wang Hospital 58 59 60 9

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 45 of 74 BMJ Open

1 2 3 Hospitals Territories Provinces City Investigator 4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Zhongnan hospital of Wuhan Yanggan 6 Central China Hubei Wuhan 7 University Wang 8 9 Fujian Provincial Hospital Eastern China Fujian Fuzhou Yansong Guo 10 11 The First Affiliated hospital of Northeast Liaoning Dalian Yanzong Yang 12 Dalian Medical University China 13 The First People's Hospital of 14 Central China Hunan Changde Yi Huang 15 Changde 16 The First Affiliated Hospital of Northeast 17 Liaoning Shenyang Yingxian Sun 18 China Medical UniversityFor peerChina review only 19 The Fourth Affiliated Hospital of Northeast 20 Liaoning Shenyang Yuanzhe Jin China Medical University China 21 22 Northern Cangzhou Central Hospital Hebei Cangzhou Zesheng Xu 23 China 24 Zewei 25 The Central Hospital of Shaoyang Central China Hunan Shaoyang 26 Ouyang 27 The People's Hospital of Liaoning Northeast 28 Liaoning Shenyang Zhanquan Li 29 Province China 30 The First Affiliated Hospital of Northeast Heilongjiang Jiamusi Zhaofa He 31 Jiamusi University China 32 33 Northern Tangshan Gongren Hospital Hebei Tangshan Zheng Ji 34 China 35

36 Huaibei Miners General Hospital Eastern China Anhui Huaibei Zhenqi Su http://bmjopen.bmj.com/ 37 38 39 Linyi People's Hospital Eastern China Shandong Linyi Zhihong Ou 40 41 42 43

44 on September 23, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 10

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 46 of 74

1 2 3 Table S4. Case Report Form of CCC-AF

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Improving Care for Cardiovascular Disease in China : 6 A collaborative project of AHA and CSC 7 Atrial Firbrillation-CRF 8 9 A. Demographics 10 Name: _____ Sex : O Male O Female Date of Birth: ______11 12Medical Record ID: _____ Personal ID: ______O Unknown Other ID: ______13 Tel.: ______Relationship of Contact Person with Patient: ______Name of Contact Person: ______14 15Tel. of the contact person:______Ethnic Group: O Han O Manchu O Zhuang O Hui O Mongol O Uyghur O Kazak O Other 16Address: Province City District Street No. O Unknown Zip code: ______O Unknown 17 Education: O Primary school or below O Middle school O High school O University/college undergraduate 18 For peer review only O Master’s degree or above O Unknown 19 20 Occupation: O Managerial, administrative or official O Professional and technical O Service O Agriculture O Manufacturing 21 O Retired O Unemployed O Others 22

23Marriage Status : O Single O Married O Divorced O Widowed O Other 24 Medical Insurance: O Urban employees-basic medical insurance O Urban residents - basic medical insurance 25 O New rural cooperative medical insurance O Commercial medical insurance O Full government-paying 26 O Self-paying O Other medical insurance O Other 27 28B. Arrival and Admission Information 29 30Department：O Cardiology O Internal medicine O Other: ______Ward Number: ______Doctor in Charge: ______31Arrival Date and Time： ___/___/______: ____ O MM/DD/YYYY only O Unknown 32 33Admit Date：___/___/______Intra-hospital transportation: O No O Yes 34Point of Origin for Admission or Visit: O Clinic O Emergency room O Transferred from another hospital O Unknown 35

36C. Medical History http://bmjopen.bmj.com/ 37 □ □ □ 38 None Heart failure Upper gastrointestinal hemorrhage 39 □ Smoker □ Family history of AF □ Gastrointestinal 40 □ Alcohol use □ Cardiac transplantation □ Other 41 □ Hypertension history □ Cardiomyopathy □ Obstructive sleep apnea 42 □ Uncontrolled, SBP > 160 mmHg □ Ischemic O CPAP 43 □ Diabetes □ Non-Ischemic □ COPD 44 □ Coronary artery disease □ Rheumatic heart disease □ Renal Disease on September 23, 2021 by guest. Protected copyright. 45 □ Prior MI □ Mechanical prosthetic heart valve □ Dialysis 46 □ Transplant 47 □ Prior PCI □ Mitral stenosis □ Cr >2.6 mg/dL or >200, μmol/L 48 Medical History □ Bare metal stent □ CVA/TIA □ Liver disease (Cirrhosis, 49 (Select all that apply) □ Drug eluting stent □ Ischemic stroke 50 □ CRT-D (cardiac resynchronization □ ICH Bilirubin >2x Normal, AST/ALT/AP >3x Normal) 51 therapy w/ICD) □ TIA □ Thyroid Disease 52 □ CRT-P (cardiac resynchronization □ Cognitive impairment □ Hyperthyroidism 53 therapy-pacing only) □ Depression 54 □ Hypothyroidism □ Pacemaker □ Peripheral arterial disease 55 □ Sinus node dysfunction/ sick sinus □ Anemia 56 □ Deep vein thrombosis syndrome □ Cancer 57 □ PIulmonary embolism □ Prior major bleeding or 58 □ LAA occlusion device 59 □ Left ventricular hypertrophy predisposition to bleeding (bleeding 60 diathesis, anemia, etc.) 11

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 47 of 74 BMJ Open

1 2 3 Labile INR? Ο Yes Ο No O Unknown

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Prior AF Procedures □ None □ Cardioversion □ Ablation □ AF surgery (Surgical MAZE) 6 7 D. Diagnosis 8 □ Atrial flutter 9 □ Valvular atrial fibrillation □ Nonvalvular atrial fibrillation 10 If Atrial Fibrillation: If Atrial Flutter: 11 O First detected atrial fibrillation O Typical atrial flutter 12 O Paroxysmal atrial fibrillation O Atypical atrial flutter O Persistent atrial fibrillation O Unknown 13Atrial Arrhythmia Type 14 (If Persistent Atrial Fibrillation,the type of your first detected atrial fibrillation 15 is: O Paroxysmal atrial fibrillation 16 O Persistent atrial fibrillation) 17 O Permanent/long standing persistent atrial fibrillation 18 O UnknownFor peer review only 19 Was Atrial Fibrillation/Flutter the patient’s primary 20 O No O Yes diagnosis? 21 22 O Acute MI O Surgery O CVA/TIA If not, what was the patient’s primary diagnosis? 23 O Heart Failure O COPD O Other 24 25 □ None □ Heart failure □ Ischemic stroke 26Were any of the following first detected on this □ Acute MI □ Liver disease □ ICH 27admission? □ Coronary artery disease □ Mitral stenosis □ TIA 28 □ Diabetes □ Peripheral aterial disease □ Pulmonary embolism 29 30E. Medications at Admission 31 32 □ Patient on no meds prior to admission □ Aspirin 33 □ Beta blocker Aspirin was used for 34 Beta blocker was used for □ Atrial fibrillation 35 □ Heart failure □ Acute coronary syndrome

36 □ Antihypertension □ Primary prevention of CVD http://bmjopen.bmj.com/ 37 □ Arrhythmia □ ACE inhibitor 38 □ Ca channel blocker □ Aldosterone antagonist 39 O Dihydropyridine □ 40 Alpha blockers 41 O Non-dihydropyridine □ Angiotensin receptor blocker (ARB) 42 □ Antiarrhythmic □ Anticoagulation Therapy 43 □ Amiodarone □ Warfarin (Coumadin)

□ Dofetilide on September 23, 2021 by guest. Protected copyright. 44 Medications Used Prior to Admission □ Dabigatran (Pradaxa) 45 □ Dronedarone □ Argatroban (Select all that apply) 46 □ Flecainide □ Apixaban (Eliquis) 47 □ Propafenone □ Desirudin (Iprivask) 48 □ Sotalol □ 49 Fondaparinux (Atrixa) □ 50 Other (Beta blocker and Ca channel blocker □ Rivaroxaban (Xarelto) 51 not included) □ Lepirudin (Refludan) 52 □ Antiplatelet agent (not aspirin) □ Other anticoagulant 53 □ Aggrenox (Dipyridamole) □ Digoxin 54 □ Brilinta (Ticagrelor) □ Diuretic 55 □ Clopidogrel □ Hydralazine Nitrate 56 □ Prasugrel (Effient) □ NSAIDS/COX-2 Inhibitor 57 □ Ticlid (Ticlopidine) □ 58 Statin □ Other 59 60 12

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 48 of 74

1 2 3 F. Exam/ Labs at Admission

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 □ No reported symptoms □ Chestpain/tightness/discomfort □ Exercise intolerance 6 Presentation Symptoms Related to AF □ Syncope □ Weakness □ Dyspnea at exertion 7 (Select all that apply) □ Fatigue □ Palpitations dyspnea at rest □ Lightheadedness/dizziness 8 9 O EHRA I No symptoms 10Classification of AF-related Symptoms (EHRA O EHRA II Mild symptoms; normal daily activity not affected 11 score) O EHRA III Severe symptoms; normal daily activity affected 12 O EHRA IV Disabling symptoms; normal daily activity discontinued 13 14 Height ______cm □ Unknown Weight ______kg □ Unknown 15Initial Vital Signs Heart Rate ______bpm □ Unknown BP ______/______mmHg (SBP/DBP) □ Unknown 16 17Initial Presenting Rhythm(s) □ Atrial fibrillation □ Sinus rhythm □ Paced 18(Select all that apply) For□ Atrial flutter peer review□ Atrial onlytachycardia □ Other 19 20If Paced, underlying Atrial Rhythm O Sinus Rhythm O Atrial fib/flutter O Sinus arrest O Not available 21If Paced, Pacing Type O Atrial pacing O Ventricular pacing O Atrial pacing 22 Automated ECG O No O Yes 23 24 Resting Heart Rate (bpm)___ □ Not Available QTc (ms) ______□ Not Available 25Initial EKG Findings QRS duration (ms)_____ □ Not Available PR interval(ms)_____ □ Not Available 26 27 LVEF _____% □ Not available 28 Obtained: O This Admission O W/in the last year O > 1 year ago 29 Echocardiography Result Left ventricular end-diastolic diameter (LVEDD):___ mm □ Not available 30 Left ventricular end-systolic diameter(LVESD):____ mm □ Not available 31 Thrombus: O No O Yes 32 Atrium Size:______mm □ Not available 33 34 Platelet Count ______g/L □ Not available Hematocrit ______% □ Not available 35 Hemoglobin ______g/L □ Not available INR ______□ Not available

36 http://bmjopen.bmj.com/ 37Labs SCr _____ O mg/dL O μmol/L □ Not available BUN ______O mg/dL Oμmol/L □ Not available 38(closest to admission) K ____O mEq/L O mmol/L O mg/dL □ Not available Mg ______O mg/dL Ommol/L □ Not available 39 TSH _____ mlU/L □ Not available BNP______O pg/mLO pmol/L O ng/L □ Not available 40 41 NT-BNP ______(pg/mL) □ Not available 42 43G. In-Hospital Care

44 on September 23, 2021 by guest. Protected copyright. □ No procedures □ CRT-D (cardiac resynchronization therapy w/ICD) 45 46 □ A-Fib ablation □ CRT-P (cardiac resynchronization therapy-pacing only) 47 □ A-Flutter ablation □ ICD only 48 If A -Fib or A -Flutter ablation selected above: □ LAA occlusion device O Cryoablation 49 □ Mechanical prosthetic heart valve Procedures during this hospitalization O Radio frequency ablation 50 □ Pacemaker □ Cardioversion (check all that apply below) 51 □ PCI/Cardiac catheterization 52 □Chemical □ Bare metal stent 53 □Electrical □ Drug eluting stent 54 □TEE guided 55 □ Surgical MAZE 56 57 58 59 60 13

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 49 of 74 BMJ Open

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from □ None □ Antiplatelet agent (not aspirin) □ Anticoagulant 5 6 □ Antiarrhythmic □ Aggrenox (Dipyridamole) □ Warfarin 7 □ Amiodarone □ Brilinta (Ticagrelor) □ Dabigatran 8 □ Dofetilide □ Clopidogrel □ Apixiban Oral Medications during hospitalization 9 □ Dronedarone □ Prasugrel (Effient) □ Rivaroxiban Select all that apply 10 □ Flecainide □ Ticlid (Ticlopidine) □ Ca channel blocker 11 □ Propafenone □ Other □ Beta Blocker 12 □ Sotalol □ Aspirin □ Digoxin 13 □ Other 14 15Parenteral In-Hospital Anticoagulation O None O Unfractionated Heparin iv. O LMW Heparin O Other iv. Anticoagulant 16CHADS2 reported?(in medical record) 17 O No O Yes, Score______18If yes, total reported score in medical record For peer review only 19H. Discharge Information 20 21Discharge Date/Time___/___/______: ____ □ MM/DD/YYYY only 22Vital Signs BP-Supine ______/______mmHg (systolic/diastolic) □ Not documented 23 24(closest to discharge) Heart Rate ______bpm □ Not documented 25Discharge Rhythm(s) □ Atrial Fibrillation □ Sinus Rhythm □ Paced 26 (closest to discharge) □ Atrial Flutter □ Atrial Tachycardia □ Other 27 28EKG findings (closest to discharge): Resting Heart Rate (bpm) □ Not Available QTc (ms) □ Not Available 29 QRS duration(ms) □ Not Available PR interval(ms) □ Not Available 30Discharge EKG QRS Morphology O Normal O RBBB O LBBB O NS-TVCD O Not Available 31 32Labs Platelet Count ______g/L □ Not Available INR ______□ Not Available

33(closest to discharge) SCr ______O mg/dL O μmol/L □ Not Available 34 35I. Discharge Medication

36 http://bmjopen.bmj.com/ Prescribed? O No O Yes 37 38 If yes, Medication: ______Dosage: ______mg Frequency:______times/day age: Frequency: 39Anticoagulation Therapy Medication: ______Dosage: ______mg Frequency:______times/day 40

41 Contraindicated? O No O Yes 42 □ Are there any relative or absolute contraindications to oral anticoagulant therapy? (Check all that apply) 43

44 □ Allergy □ Unable to adhere/monitor on September 23, 2021 by guest. Protected copyright. 45 □ High bleeding risk □ Occupational risk 46 □ Comorbid illness (e.g. renal/liver) 47 □ Prior intracranial hemorrhage □ Need for dual antiplatelet □ Patient refusal/preference 48 □ Bleeding Event □ Current pregnancy 49 □ Frequent falls/frailty 50 51 □ Physician preference 52 □ Recent operation therapy 53 Prescribed? O No O Yes 54 55Aspirin If yes, Medication: ______Dosage: ______mg Frequency:______times/day 56 Contraindicated? O No O Yes 57 Prescribed? O No O Yes 58 59Other Antiplatelet(s) If yes, Medication: ______Dosage: ______mg Frequency:______times/day 60 Medication: ______Dosage: ______mg Frequency:______times/day 14

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 50 of 74

1 2 3 Contraindicated? O No O Yes

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Prescribed? O No O Yes 6Beta Blocker If yes, Medication: ______Dosage: ______mg Frequency:______times/day 7 Contraindicated? O No O Yes 8 9 Prescribed? O No O Yes 10Calcium Channel Blocker If yes, Medication: ______Dosage: ______mg Frequency:______times/day 11 Contraindicated? O No O Yes 12 13 Prescribed? O No O Yes 14 Medication: ______Dosage: ______mg Frequency:______times/day If yes, 15Other Antiarrhythmic 16 Were Dofetilide or Sotalol newly initiated or dose increased this hospitalization? O No O Yes 17 18 If yes, was a QTFor interval documented peer after 5 dosesreview and prior to discharge? only O No O Yes 19 Prescribed? O No O Yes 20 ACEI If yes, Medication: ______Dosage: ______mg Frequency:______times/day 21 22 Contraindicated? O No O Yes 23 Prescribed? O No O Yes 24 ARB If yes, Medication: ______Dosage: ______mg Frequency:______times/day 25 26 Contraindicated? O No O Yes 27 Prescribed? O No O Yes 28 Aldosterone Antagonist If yes, Medication: ______Dosage: ______mg Frequency:______times/day 29 30 Contraindicated? O No O Yes 31 Prescribed? O No O Yes 32 33Digoxin If yes, Medication: ______Dosage: ______mg Frequency:______times/day 34 Contraindicated? O No O Yes 35 Prescribed? O No O Yes

36Statin Therapy http://bmjopen.bmj.com/ 37 Contraindicated? O No O Yes 38 Prescribed? O No O Yes Hydralazine Nitrate 39 Contraindicated? O No O Yes 40 41 □ Diuretic O No O Yes □ NSAIDS/COX-2 Inhibitor O No O Yes Other Medications at Discharge 42 43

44J. Risk Interventions on September 23, 2021 by guest. Protected copyright. 45 46Smoking Cessation Counseling Given O No/ Not Documented O Yes O Not Applicable 47Rhythm Control/Rate Control Strategy O Rhythm Control Strategy Planned O Rate Control Strategy Planned O No Documentation of Strategy 48Planned/Intended 49 50Patient and/or caregiver received education □ All were addressed (Check all yes) 51and/or resource materials regarding all of the Risk factors O No O Yes Stroke Risk O No O Yes 52following: Management O No O Yes Medication Adherence O No O Yes 53 54 Follow-up O No O Yes When to call provide O No O Yes 55Anticoagulation Therapy Education Given O No O Yes 56 57 58 59 60 15

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 51 of 74 BMJ Open

1 2 3PT/INR Planned Follow-up O No O Yes Who will be following patients INR? O Home INR Monitoring

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 O Anticoagulation Warfarin Clinic 6 O Managed by Physician associated with hospital 7 O Managed by outside physician 8 9 O Not documented 10 Date of INR test planned post discharge: ___/___/______□ Not Documented 11 12 System Reason for no PT/INR Planned Follow-up O No O Yes 13 14 15TLC (Therapeutic Lifestyle Change) Diet O No/ Not Documented O Yes O Not Applicable 16Obesity Weight Management O No/ Not Documented O Yes O Not Applicable 17 Activity Level/Recommendation O No/ Not Documented O Yes O Not Applicable 18 For peer review only 19Screening for obstructive sleep apnea (Berlin O No/ Not Documented O Yes O Not Applicable 20Questionnaire) 21 Referral for evaluation of obstructive sleep O No/ Not Documented O Yes O Not Applicable 22 23apnea if positive screen 24Discharge medication instruction provided O No/ Not Documented O Yes O Not Applicable 25 26K. Admin 27 Principal Diagnosis:______Principal Diagnosis Code:______28 29Other Diagnose 1: ______Other Diagnose Code1:______30Other Diagnose 2: ______Other Diagnose Code2:______31 Other Diagnose 3: ______Other Diagnose Code 3:______32 33Other Diagnose 4: ______Other Diagnose Code 4:______34Other Diagnose 5: ______Other Diagnose Code 5:______35 Other Diagnose 6: ______Other Diagnose Code 6:______

36 http://bmjopen.bmj.com/ 37Other Diagnose 7: ______Other Diagnose Code 7:______38Principal Procedure:______Principal Procedure Code:______Date: ___/___/____ □ Date UTD 39 Other Procedure 1:______Other Procedure Code 1:______Date: ___/___/____ □ Date UTD 40 41Other Procedure 2:______Other Procedure Code 2:______Date: ___/___/____ □ Date UTD 42Other Procedure 3:______Other Procedure Code 3:______Date: ___/___/____ □ Date UTD 43 Other Procedure 4:______Other Procedure Code 4:______Date: ___/___/____ □ Date UTD

44 on September 23, 2021 by guest. Protected copyright. 45During this hospital stay, was the patient enrolled in a clinical trial in which patients with the same condition as the measure set were being studied? O No O Yes 46 L. CHADS2 Calculation Tool 47

48(Enabled if “No” is selected for CHADS2 Reported (in medical record)?) 49 □ Prior stroke or TIA 50 51 □ Age> 75 52 □ Hypertension 53 □ Diabetes 54 55 □ Congestive Heart Failure 56 57M. Other Risk Scores 58 59NOTE: CHADS2-VASc is an extension of the CHADS2 score. It contains additional risk categories and can be used as a complimentary tool in the assessment of 60thromboembolic risk in atrial fibrillation patients. The AHA/ACC Guidelines support the use of the CHADS2 score in assessment of thromboembolic risk and 16

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 52 of 74

1 2 3 indication for anticoagulation therapy is stratified using the CHADS2 score.

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 CHADS2-VASc Score □ Congestive Heart Failure 6 7 □ Diabetes 8 □ Hypertension (blood pressure consistently above 140/90 or treated with hypertension medication) 9 □ Prior stroke/TIA/Thromboembolism 10 11 □ Age≥75 12 □ Vascular Disease History (CAD, Prior MI, or PAD) 13 □ Age 65-74 14 □ 15 16Adapted from a methodology used by the American College of Chest Physicians: Lip GY, Niewlatt R, Pisters R, Lane DA, Crijns HJ, et al. Refining clinical risk stratification for predicting stroke and 17thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. CHEST 2010 Feb;137(2):263-72. doi: 18 For peer review only 10.1378/chest.09-1584. Epub 2009 Sep 17. http://journal.publications.chestnet.org/article.aspx?articleid=1045174 19 20 DISCLAIMER: These tools (ATRIA and HAS-BLED) are presented for informational purposes only and not as an endorsement of their use in clinical decision making. Many 21 22of the same risk factors for warfarin-related hemorrhage are also risk factors for AF-associated ischemic stroke. The use of these tools as an exclusion for anticoagulation 23is not part of AHA/ACC guideline-recommended care for patients with AF. Additionally, some of the component elements in the HAS-BLED score, such as Labile INR and 24 Prior Major Bleeding or Pre-Disposition to Bleeding may be difficult to reliably ascertain from the information available in the health record. The HAS- BLED score should 25 26be interpreted with this in mind. 27 28ATRIA Risk Score □ Age ≥ 75 years 29 □ 30 Anemia (Defined as Hemoglobin < 13 g/dL in men and < 12 g/dL in women) 31 □ History of Hypertension 32 □ Severe Renal Disease (defined as a GFR < 30ml/min or on dialysis) 33 □ Prior hemorrhage (intracranial, gastrointestinal, other hemorrhage) 34 35Adapted from a methodology used by the American College of Cardiology: Fang MC, Go AS, Chang Y, et al. A New Risk Scheme to Predict Warfarin-Associated

36Hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 2011;58(4):395-401. doi:10.1016/j.jacc.2011.03.031. http://bmjopen.bmj.com/ 37 http://content.onlinejacc.org/article.aspx?articleid=1146658#Abstract 38 39 40 HAS-BLED Score □Age 41 42 □ Hypertension History (uncontrolled, >160 mmHg systolic) 43 □ Renal Disease (Dialysis, transplant, Cr >2.6 mg/dL or >200 μmol/L)

44 on September 23, 2021 by guest. Protected copyright. 45 □ Liver Disease (Chronic Hepatic Disease, including (e.g.) Cirrhosis, Bilirubin >2x Normal, AST/ALT/AP >3x Normal) 46 □ Stroke History 47 □ Prior Major Bleeding or Predisposition to Bleeding (bleeding diathesis, anemia, etc.) 48 □ 49 Labile INR (Unstable/high INRs or time in therapeutic range <60%) 50 □ Age > 65 51 □ Medication Usage Predisposing to Bleeding (Antiplatelet agents, NSAIDs) 52 □ Alcohol Usage History (>20 units per week) 53 54Adapted from a methodology used by the American College of Chest Physicians: Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HM, Lip GH. A novel user-friendly score 55(has-bled) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the euro heart survey. Chest, 2010;138(5):1093-1100. 56 http://journal.publications.chestnet.org/article.aspx?articleid=1086288 57 58 59 60 17

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 53 of 74 BMJ Open

1 2 3 Table S5. Definition of Primary Performance Measures

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 6 Primary performance measure 1: 7 8 Proportion of patients with nonvalvular atrial fibrillation in whom assessment of 9 thromboembolic risk 10 11 The proportion of patients with nonvalvular atrial fibrillation in whom assessment of 12 thromboembolic risk using CHADS2 or CHA2DS2-VASc score have been documented in medical 13 records. 14 15 AF patients reporting CHADS2 or CHA2DS2-VASc risk score to assess the 16 thromboembolic risk factors. 17 18 Numerator ForRelevant peer data elements: review only 19 (CHADS =“Yes” and CHADS score is not NA), or(CHA DS -VASc 20 2 2 2 2 21 score=“Yes” and CHA2DS2 –VASc score is not NA） 22 23 Include: 24 25 Nonvalvular AF patients 26 Relevant data elements: 27 28 Atrial arrhythmia type=“Nonvalvular atrial fibrillation” 29 30 Exclude: 31 ① Patients with a medical history of mitral stenosis or a mechanical 32 prosthetic heart valve 33 34 ② Patients who are newly diagnosed with mitral stenosis this 35 hospitalization Denominator 36 ③ Patients who have a mechanic prosthetic heart valve implanted http://bmjopen.bmj.com/ 37 during their hospitalization 38 39 ④ Patients for whom there is a documented contraindication to 40 anticoagulation therapy 41 42 Relevant data elements: 43 ① Medical history of mitral stenosis=“Yes” or mechanic prosthetic 44 on September 23, 2021 by guest. Protected copyright. 45 heart valve=“Yes” 46 ② Mitral stenosis =“Yes” 47 ③ Mechanic prosthetic heart valve=“Yes” 48 ④ Contraindication to anticoagulation therapy=“Yes” 49 50 51 Evaluation time At discharge 52 53 Data sources Case records 54 55 Reasons for evaluation 56 57 The assessment of thromboembolic risk factors according to baseline characters is the foundation 58 to make right decisions for anticoagulation therapy. 59 60 18

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 54 of 74

1 2 3 Guidelines

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 AHA/ACC 2014 AF guidelines 6 7 Class I 8 In patients with nonvalvular AF, the CHA2DS2-VASc score is recommended for assessment of 9 stroke risk. (Level of evidence: B) 10 In patients with AF, antithrombotic therapy should be individualized based on shared decision 11 making after discussion of the absolute and RRs of stroke and bleeding, and the patient’s values 12 13 and preferences. (Level of Evidence: C) 14 For patients with atrial flutter, antithrombotic therapy is recommended according to the same 15 risk profile used for AF. (Level of Evidence: C) 16 ESC 2010 AF guidelines 17 18 Class I For peer review only

19 The CHADS2 [cardiac failure, hypertension, age, diabetes, stroke (doubled)] score is 20 recommended as a simple initial (easily remembered) means of assessing stroke risk in 21 non-valvular AF. (Level of Evidence: A) 22 23 Ways of reporting 24 25 Percentages and numerator/denominator 26 27 28 29 30 31 32 33 34 35

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 23, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 19

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 55 of 74 BMJ Open

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Primary performance measure 2： 6 Proportion of AF patients with indication prescribed an anticoagulant drug at hospital 7 8 discharge 9 10 AF patients receiving warfarin, dabigatran, argatroban or rivaroxaban at 11 12 discharge 13 Relevant data elements: 14 Numerator 15 Anticoagulation therapy=“Yes”, and 16 Warfarin=“Yes” or dabigatran=“Yes” or argatroban=“Yes” or 17 18 For peerrivaroxaban=“Yes” review only 19 Include: 20 21 Nonvalvular AF patients with CHA2DS2-VASc≥2 22 23 Relevant data elements: 24 25 Atrial arrhythmia type=“Nonvalvular atrial fibrillation”, and 26 27 CHA2DS2-VASc score ≥2 28 Exclude: 29 30 ① Patients with a medical history of mitral stenosis or a mechanical 31 prosthetic heart valve 32 ② Patients who are newly diagnosed with mitral stenosis this 33 34 hospitalization 35 ③ Patients who have a mechanic prosthetic heart valve implanted

36 during their hospitalization http://bmjopen.bmj.com/ 37 Denominator ④ Patients for whom there is a documented contraindication to 38 39 anticoagulation therapy 40 ⑤ Expire during hospitalization 41 Relevant data elements: 42 43 ① Mitral stenosis=“Yes”or mechanic prosthetic heart valve=“Yes” 44 ② Mitral stenosis=“Yes” on September 23, 2021 by guest. Protected copyright. 45 46 ③ Mechanic prosthetic heart valve=“Yes” 47 ④ Contraindication to anticoagulation therapy=“Yes” or any of the 48 following is “Yes”: allergy, occupational risk, prior intracranial 49 hemorrhage, bleeding event, frequent falls/frailty, recent 50 51 operation therapy, unable to adhere/monitor, high bleeding risk, 52 comorbid illness (e.g. renal/liver), patient refusal/preference, or 53 current pregnancy 54 ⑤ Expire=“Yes” 55 56 57 Evaluation time At discharge 58 59 Data sources Case records 60 20

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 56 of 74

1 2 3 Reasons for evaluation

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 6 The reasonable anticoagulation therapy can better the quality of life and long-term prognosis of AF 7 patients. 8 9 Guidelines 10 11 AHA/ACC 2014 AF guidelines 12 Class I 13 For patients with nonvalvular AF with prior stroke, transient ischemic attack (TIA), or a CHA DS - VASc 14 2 2 15 score of 2 or greater, oral anticoagulants are recommended. Options include: 16  Warfarin (INR 2.0 to 3.0) (Level of Evidence: A) 17  Dabigatran, rivaroxaban or apixaban (Level of Evidence: B) 18 For patients with atrialFor flutter, peer antithrombotic review therapy is recommended only according to the same risk 19 profile used for AF. (Level of Evidence: C) 20 21 Class IIa 22 For patients with nonvalvular AF and a CHA DS -VASc score of 0, it is reasonable to omit 23 2 2 antithrombotic therapy (81, 82). (Level of Evidence: B) 24 25 Class IIb 26 For patients with nonvalvular AF and a CHA DS -VASc score of 1, no antithrombotic therapy or 27 2 2 28 treatment with an oral anticoagulant or aspirin may be considered. (Level of Evidence: C ) 29 ESC 2010 AF guidelines 30 31 Class I 32 For the patients with a CHADS2 score of >= 2, chronic oral anticoagulant (OAC) therapy with a vitamin 33 K antagonist (VKA) is recommended in a dose adjusted regimen to achieve an INR range of 2.0–3.0 34 (target 2.5), unless contraindicated. (Level of Evidence: A) 35

36 Ways of reporting http://bmjopen.bmj.com/ 37 38 Percentages and numerator/denominator 39 40 41 42 43

44 on September 23, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 21

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 57 of 74 BMJ Open

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Primary performance measure 3： 6 Proportion of patients discharged on warfarin who have PT/INR follow-up planned 7 8 prior to hospital discharge 9 10 The proportion of patients discharged on warfarin who have PT/INR follow-up planned prior to 11 hospital discharge. 12 13 Patients who have PT/INR follow-up planned prior to hospital discharge 14 Numerator Relevant data elements: 15 16 PT/INR follow-up plan=“Yes” 17 18 ForInclude: peer review only 19 20 Patients discharged on warfarin 21 Relevant data elements: 22 23 Anticoagulation therapy=“Yes”, and warfarin=“Yes” 24 Exclude: 25 Denominator 26 ① System reason for no PT/INR planned follow-up 27 ② Expire during hospitalization 28 29 Relevant data elements: 30 ① System reason for no PT/INR planned follow-up=“Yes” 31 ② Expire=“Yes” 32 33 34 Evaluation time At discharge 35

36 Data sources Case records http://bmjopen.bmj.com/ 37 38 Reasons for evaluation 39 40 Regular anticoagulation therapy, PT/INR planned follow-up and systematic anticoagulation 41 management can lower the risk of thromboembolism and bleeding events. 42 43 Guidelines 44 on September 23, 2021 by guest. Protected copyright. 45 AHA/ACC 2014 AF guidelines 46 Class I 47 48 Among patients treated with warfarin, the INR should be determined at least weekly during initiation 49 of antithrombotic therapy and at least monthly when anticoagulation (INR in range) is stable. (Level of 50 Evidence: A) 51 52 For patients with nonvalvular AF unable to maintain a therapeutic INR level with warfarin, use of a 53 54 direct thrombin or factor Xa inhibitor (dabigatran, rivaroxaban, or apixaban) is recommended. (Level 55 of Evidence: C) 56 57 Ways of reporting 58 59 Percentages and numerator/denominator 60 22

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 58 of 74

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Primary performance measure 4： 6 Proportion of AF patients with indications receiving ACEI/ARB at discharge 7 8 The proportion of AF patients with indications receiving ACEI/ARB at discharge 9 10 The indications refer to: the diagnosis with AMI during this hospitalization; the diagnosis with 11 coronary heart disease during this hospitalization and the comorbidity of hypertension, diabetes 12 mellitus or chronic kidney disease; LVEF<40% according to the case records. 13 14 AF patients receiving ACEI or ARB at discharge 15 16 Numerator Relevant data elements: 17 ACEI =“Yes”， or ARB =“Yes” 18 For peer review only 19 20 Include: 21 AF patients with the following indications: 22 23 ① Patients who are newly diagnosed with AMI this hospitalization； 24 or 25 26 ② Patients who are diagnosed with coronary heart disease during 27 their hospitalization and the comorbidity of hypertension, 28 diabetes mellitus or chronic kidney disease； or 29 30 ③ LVEF<40% according to the case records 31 32 Relevant data elements: 33 34 ① AMI=“Yes”； or 35 Denominator ② Coronary heart disease=“Yes”, and （a medical history of

36 http://bmjopen.bmj.com/ 37 hypertension=“Yes”, or diabetes mellitus=“Yes”, or 38 kidney disease=“Yes”）; or 39 ③ LVEF< 40% 40 41 Exclude: 42 43 ① Contraindication to ACEI and ARB

44 ② Expire during hospitalization on September 23, 2021 by guest. Protected copyright. 45 46 Relevant data elements:

47 48 ① Contraindication to ACEI=“Yes”， and Contraindication to ARB 49 =“Yes” 50 ② Expire=“Yes” 51 52 Evaluation time At discharge 53 54 55 Data sources Case records 56 57 Reasons for evaluation 58 59 ACEI/ARB can lower the recurrence risk of AF. 60 23

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 59 of 74 BMJ Open

1 2 3 Guidelines

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 6 AHA/ACC 2014 AF guidelines 7 Class IIa 8 An ACE inhibitor or angiotensin-receptor blocker (ARB) is reasonable for primary prevention of 9 10 new-onset AF in patients with HF with reduced LVEF. (Level of Evidence: B) 11 12 Class IIb 13 Therapy with an ACE inhibitor or ARB may be considered for primary prevention of new-onset AF 14 in the setting of hypertension (34, 151). (Level of Evidence: B) 15 16 Class III: No Benefit 17 18 Therapy with an ACEFor inhibitor, peer ARB, or statin review is not beneficial foronly primary prevention of AF in 19 patients without cardiovascular disease. (Level of Evidence: B) 20 21 AHA/ACC 2014 NSTE-ACS guidelines 22 CLASS I 23 24 1. ACE inhibitors should be started and continued indefinitely in all patients with LVEF less than 25 26 0.40 and in those with hypertension, diabetes mellitus, or stable CKD, unless contraindicated. 27 (Level of Evidence: A) 28 29 2. ARBs are recommended in patients with HF or MI with LVEF less than 0.40 who are ACE 30 inhibitor intolerant . (Level of Evidence: A) 31 32 3. Aldosterone blockade is recommended in patients post-MI without significant renal 33 dysfunction (creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) or hyperkalemia (Kþ >5.0 34 35 mEq/L) who are receiving therapeutic doses of ACE inhibitor and beta blocker and have a LVEF

36 0.40 or less, diabetes mellitus, or HF. (Level of Evidence: A) http://bmjopen.bmj.com/ 37 38 Ways of reporting 39 40 Percentages and numerator/denominator 41 42 43

44 on September 23, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 24

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 60 of 74

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Primary performance measure 5: 6 Proportion of AF patients with indication prescribed a beta blocker at hospital 7 8 discharge 9 10 The proportion of AF patients with indication prescribed a beta blocker at hospital discharge. 11 12 The indication refers to heart failure. 13 14 AF patients receiving beta blocker at discharge 15 Numerator Relevant data elements: 16 17 Beta blocker=“Yes” 18 For peer review only 19 Include: 20 21 AF patients with heart failure 22 23 Relevant data elements: 24 Were any of the following first detected on this admission？Heart 25 26 failure =“Yes” 27 Denominator 28 Exclude: 29 ① Contraindication to beta blocker 30 ② Expire during hospitalization 31 32 Relevant data elements: 33 34 ① Contraindication to beta blocker=“Yes” 35 ② Expire=“Yes” 36 http://bmjopen.bmj.com/ 37 38 Evaluation time At discharge 39 40 Data sources Case records 41 42 Reasons for evaluation 43

44 Beta blocker can lower the all-cause mortality and cardiovascular mortality of AF patients. on September 23, 2021 by guest. Protected copyright. 45 46 47 Guidelines 48 ESC 2010 AF guidelines 49 50 Class I 51 Blockers are recommended as first-line therapy to control the ventricular rate in patients with 52 heart failure and low LVEF. (Level of Evidence: A) 53 54 AHA/ACC 2014 AF guidelines 55 Class I 56 57 Control of resting heart rate using either a beta blocker or a nondihydropyridine calcium channel 58 antagonist is recommended for patients with persistent or permanent AF and compensated HF 59 with preserved EF (HFpEF) (96). (Level of Evidence: B) 60 25

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 61 of 74 BMJ Open

1 2 3 In the absence of pre-excitation, intravenous beta blocker administration (or a

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 nondihydropyridine calcium channel antagonist in patients with HFpEF) is recommended to slow 6 the ventricular response to AF in the acute setting, with caution needed in patients with overt 7 congestion, hypotension, or HF with reduced LVEF (180-183). (Level of Evidence: B) 8 9 10 Ways of reporting 11 Percentages and numerator/denominator 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 23, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 26

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 62 of 74

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Primary performance measure 6： 6 Proportion of AF patients with indication prescribed a statin at hospital discharge 7 8 9 The proportion of AF patients with coronary heart disease, ischemic stroke/TIA, peripheral 10 vascular disease (or diabetes mellitus) prescribed a statin at hospital discharge 11 12 AF patients receiving statin at discharge 13 14 Numerator Relevant data elements: 15 Statin=“Yes” 16 17 Include: 18 For peerAF patients withreview coronary heart onlydisease, ischemic stroke/TIA, 19 peripheral vascular disease (or diabetes mellitus) 20 21 Relevant data elements: 22 23 In the medical history, coronary heart disease, peripheral vascular

24 disease, ischemic stroke, TIA or diabetes mellitus=“Yes” or during 25 this hospitalization，coronary heart disease, diabetes mellitus, Denominator 26 peripheral vascular disease, ischemic stroke or TIA=“Yes” 27 Exclude: 28 29 ① Contraindication to statin 30 ② Expire during hospitalization 31 32 Relevant data elements: 33 ① Contraindication to statin=“Yes” 34 ② Expire=“Yes” 35

36 http://bmjopen.bmj.com/ 37 Evaluation time At discharge 38 39 Data sources Case records 40 41 Reasons for evaluation 42 43 NA

44 Guidelines on September 23, 2021 by guest. Protected copyright. 45 46 AHA/ACC 2014 AF guidelines 47 Class IIb 48 49 Statin therapy may be reasonable for primary prevention of new-onset AF after coronary artery 50 surgery. (Level of Evidence: A) 51 52 Class III: No Benefit 53 Therapy with an ACE inhibitor, ARB, or statin is not beneficial for primary prevention of AF in 54 patients without cardiovascular disease. (Level of Evidence: B) 55 56 ACC F/ AHA 2013 STEMI guidelines 57 58 Class I 59 High-intensity statin therapy should be initiated or continued in all patients with STEMI and no 60 27

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 63 of 74 BMJ Open

1 2 3 contraindications to its use. (Level of Evidence: B)

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 AHA/ACC 2014 NSTE- guidelines 6 Class I 7 8 High-intensity statin therapy should be initiated or continued in all patients with NSTE-ACS and 9 no contraindications to its use. (Level of Evidence: A) 10 11 Ways of reporting 12 13 Percentages and numerator/denominator 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 23, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 28

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 64 of 74

1 2 3

4 Table S6. Definition of Secondary Performance Measures BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 6 7 Secondary performance measure 1： 8 9 Proportion of nonvalvular AF patients who had a CHADS2 score reported 10 The proportion of nonvalvular AF patients who had a CHADS score reported to assess the risk of 11 2 12 thromboembolism 13 The nonvalvular AF patients who had a CHADS2 score reported 14 Numerator Relevant data elements: 15 CHADS =“Yes” and CHADS score is not NA 16 2 2 17 18 ForInclude: peer review only 19 Nonvalvular AF patients 20 Relevant data elements: 21 22 Atrial arrhythmia type=“Nonvalvular atrial fibrillation” 23 Exclude: 24 25 ①Patients with a medical history of mitral stenosis or a mechanical 26 prosthetic heart valve 27 28 ②Patients who are newly diagnosed with mitral stenosis this 29 Denominator hospitalization 30 ③Patients who have a mechanic prosthetic heart valve implanted 31 during their hospitalization 32 33 ④Patients for whom there is a documented contraindication to 34 anticoagulation therapy 35 Relevant data elements: 36 http://bmjopen.bmj.com/ 37 ① Mitral stenosis=“Yes”or mechanic prosthetic heart valve=“Yes” 38 ② Mitral stenosis=“Yes” 39 40 ③ Mechanic prosthetic heart valve=“Yes” 41 ④ Contraindication to anticoagulation therapy=“Yes” 42 43 Evaluation time At discharge

44 on September 23, 2021 by guest. Protected copyright. 45 46 Data sources Case records 47 48 Reasons for evaluation 49 The assessment of thromboembolic risk factors according to baseline characters is the foundation 50 51 to make right decisions for anticoagulation therapy. 52 Guidelines 53 54 ESC 2010 AF guidelines 55 Class I 56 The CHADS [cardiac failure, hypertension, age, diabetes, stroke (doubled)] score is 57 2 58 recommended as a simple initial (easily remembered) means of assessing stroke risk in 59 non-valvular AF. (Level of Evidence: A) 60 29

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 65 of 74 BMJ Open

1 2 3 Ways of reporting

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Percentages and numerator/denominator 6 7 8 9 10 11 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 23, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 30

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 66 of 74

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Secondary performance measure 2： 6 Proportion of nonvalvular AF patients who had a CHA DS -VASc score reported 7 2 2 8 The proportion of nonvalvular AF patients who had a CHA2DS2-VASc score reported to assess the 9 risk of thromboembolism 10 11 The nonvalvular AF patients who had a CHA2DS2-VASc score reported 12 Numerator Relevant data elements: 13 14 CHA2DS2-VASc score=“Yes”, and CHA2DS2-VASc score is not NA 15 Include: 16 17 Nonvalvular AF patients 18 ForRelevant peer data elements: review only 19 20 Atrial arrhythmia type=“Nonvalvular atrial fibrillation” 21 Exclude: 22 ① Patients with a medical history of mitral stenosis or a mechanical 23 prosthetic heart valve 24 25 ② Patients who are newly diagnosed with mitral stenosis this 26 hospitalization 27 Denominator ③ Patients who have a mechanic prosthetic heart valve implanted 28 during their hospitalization 29 30 ④ Patients for whom there is a documented contraindication to 31 anticoagulation therapy 32 Relevant data elements: 33 34 ① Medical history of mitral stenosis=“Yes”or mechanic prosthetic 35 heart valve=“Yes”

36 http://bmjopen.bmj.com/ ② Mitral stenosis =“Yes” 37 38 ③ Mechanic prosthetic heart valve=“Yes” 39 ④ Contraindication to anticoagulation therapy=“Yes” 40 41 Evaluation time At discharge 42 43 Data sources Case records

44 on September 23, 2021 by guest. Protected copyright. 45 Reasons for evaluation 46 47 The assessment of thromboembolic risk factors according to baseline characters is the foundation 48 49 to make right decisions for anticoagulation therapy. 50 51 Guidelines 52 53 AHA/ACC 2014 AF guidelines 54 Class I 55 In patients with nonvalvular AF, the CHA2DS2-VASc score is recommended for assessment of 56 stroke risk. (Level of evidence: B) 57 58 In patients with AF, antithrombotic therapy should be individualized based on shared decision 59 making after discussion of the absolute and RRs of stroke and bleeding, and the patient’s values 60 and preferences. (Level of Evidence: C) 31

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 67 of 74 BMJ Open

1 2 3 For patients with atrial flutter, antithrombotic therapy is recommended according to the same

4 risk profile used for AF. (Level of Evidence: C) BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 6 Ways of reporting 7 8 Percentages and numerator/denominator 9 10 11 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 23, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 32

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 68 of 74

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Secondary performance measure 3： 6 Proportion of AF patients who have a documented resting heart rate of <80 bpm 7 8 closest to hospital discharge 9 The proportion of AF patients who have a documented resting heart rate of <80 bpm closest to 10 11 hospital discharge 12 AF patients who have a documented resting heart rate of <80 bpm closest 13 to hospital discharge 14 Numerator 15 Relevant data elements: 16 Resting heart rate(bpm) <80 17 18 ForInclude: peer review only 19 20 Nonvalvular AF patients 21 22 Relevant data elements: 23 Atrial arrhythmia type =“Nonvalvular atrial fibrillation” 24 25 Denominator Exclude: 26 ① Data missing of resting heart rate closest to hospital discharge 27 28 ② Expire during hospitalization 29 30 Relevant data elements: 31 ① Resting heart rate(bpm) is NA 32 ② Expire=“Yes” 33 34 Evaluation time At discharge 35

36 Data sources Case records http://bmjopen.bmj.com/ 37 38 Reasons for evaluation 39 40 Rate control can better cardiac function and lower the risk of thromboembolism. 41 42 43 Guidelines

44 on September 23, 2021 by guest. Protected copyright. 45 AHA/ACC 2014 AF guidelines 46 Class IIa 47 48 A heart rate control (resting heart rate <80 bpm) strategy is reasonable for symptomatic 49 management of AF. (Level of Evidence: B) 50 51 Class IIb 52 A lenient rate-control strategy (resting heart rate <110 bpm) may be reasonable as long as 53 patients remain asymptomatic and LV systolic function is preserved. (Level of Evidence: B) 54 55 56 Ways of reporting 57 Percentages and numerator/denominator 58 59 60 33

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 69 of 74 BMJ Open

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Secondary performance measure 4： 6 Proportion of providing anticoagulation therapy education 7 8 The proportion of AF patients who receive anticoagulation drugs at discharge that receiving 9 anticoagulation therapy education during the hospitalization 10 The anticoagulation therapy education refers to receiving education about anticoagulation 11 12 therapy or education materials: the effect of anticoagulation drugs, the meaning of TNR planned 13 follow-up and the side effect of anticoagulation drugs. 14 15 AF patients that receiving anticoagulation therapy education 16 Numerator Relevant data elements: 17 18 For peerAnticoagulation review therapy education only=“Yes” 19 Include: 20 Patients that receiving anticoagulation therapy at discharge 21 22 Relevant data elements: 23 Anticoagulation therapy=“Yes” 24 Denominator 25 Exclude: 26 Expire during hospitalization 27 28 Relevant data elements: 29 Expire=“Yes” 30 31 Evaluation time At discharge 32 33 34 Data sources Case records 35

36 Reasons for evaluation http://bmjopen.bmj.com/ 37 38 Regular anticoagulation therapy, PT/INR planned follow-up and systematic anticoagulation 39 management can lower the risk of thromboembolism and bleeding events. The anticoagulation 40 41 therapy education is helpful to patients’ compliance and prognosis. 42 43 Guidelines

44 on September 23, 2021 by guest. Protected copyright. 45 NA 46 Ways of reporting 47 48 Percentages and numerator/denominator 49 50 51 52 53 54 55 56 57 58 59 60 34

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 70 of 74

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Secondary performance measure 5： 6 Proportion of AF patients that receiving conventional medical education 7 8 9 The proportion of AF patients that receiving the following conventional medical education: risk 10 factors, risk of stroke, management, compliance of drugs, follow-up and when to seek medical 11 help 12 13 14 AF patients that receiving three or more of the following medical education 15 during hospitalization: risk factors, stroke risk, management, medication 16 adherence, follow-up and when to call provide. 17 Numerator 18 ForRelevant peer data elements: review only 19 20 Three or more of risk factors, management, follow-up, stroke risk, 21 22 medication adherence and when to call provide are “Yes” 23 24 Include: 25 AF patients 26 Exclude: 27 Denominator Expire during hospitalization 28 29 Relevant data elements: 30 Expire=“Yes” 31 32 Evaluation time At discharge 33 34 35 Data sources Case records

36 http://bmjopen.bmj.com/ 37 Reasons for evaluation 38 39 The medical education during hospitalization about risk factors, stroke risk, management, 40 medication adherence, follow-up and when to call provide is helpful to patients’ compliance and 41 42 prognosis. 43

44 Guidelines on September 23, 2021 by guest. Protected copyright. 45 46 NA 47 Ways of reporting 48 49 Percentages and numerator/denominator 50 51 52 53 54 55 56 57 58 59 60 35

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 71 of 74 BMJ Open

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Secondary performance measure 6: 6 7 Proportion of AF patients with indication prescribed aldosterone antagonist at 8 discharge 9 10 The proportion of AF patients with indication prescribed aldosterone antagonist at discharge. 11 12 The indications refer to: the patient was diagnosed with AMI during this hospitalization with 13 14 LVEF<40% or heart failure or diabetes mellitus; OR, the heart failure patients with LVEF<35%. 15 16 AF patients prescribed aldosterone antagonist 17 Relevant data elements: 18 Numerator For peer review only 19 Aldosterone antagonist =“Yes” 20 21 Included: 22 23 ① The patient was diagnosed with AMI during this hospitalization with 24 LVEF<40% or heart failure or diabetes mellitus; or 25 ② The heart failure patients with LVEF<35%. 26 27 Relevant data elements: 28 ① AMI=“Yes”， and ( LVEF < 40% , or a medical history of heart 29 failure=“Yes” or a medical history of diabetes mellitus=“Yes”, or 30 heart failure=“Yes” or diabetes mellitus=“Yes”）; or 31 32 ② LVEF< 35% , and ( a medical history of heart failure=“Yes” or heart 33 Denominator failure=“Yes”) 34 Excluded population: 35

36 ① Contraindication to aldosterone antagonist http://bmjopen.bmj.com/ 37 ② Expire during hospitalization 38 39 ③ With chronic kidney disease 40 Relevant data elements: 41 42 ① Contraindication to aldosterone antagonist= “Yes” 43 ② Expire=“Yes”

44 on September 23, 2021 by guest. Protected copyright. 45 ③ Kidney disease=“Yes” 46 47 Evaluation time At discharge 48 49 Data sources Case records 50 51 52 Reasons for evaluation 53 NA 54 55 Guidelines 56 ACC F/ AHA 2013 STEMI guidelines 57 58 Class I 59 An aldosterone antagonist should be given to patients with STEMI and no contraindications who 60 36

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 72 of 74

1 2 3 are already receiving an ACE inhibitor and beta blocker and who have an EF less than or equal to

4 0.40 and either symptomatic HF or diabetes mellitus. (Level of Evidence: B) BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 6 AHA/ACC 2014 NSTE-ACS guidelines 7 CLASS I 8 9 Aldosterone blockade is recommended in patients post-MI without significant renal dysfunction 10 (creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) or hyperkalemia (Kþ >5.0 mEq/L) who 11 12 are receiving therapeutic doses of ACE inhibitor and beta blocker and have a LVEF 0.40 or less, 13 diabetes mellitus, or HF. (Level of Evidence: A) 14 15 Ways of reporting 16 Percentages and numerator/denominator 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 23, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 37

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 73 of 74 BMJ Open

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Secondary performance measure 7： 6 Proportion valvular AF patients prescribed warfarin at hospital discharge 7 8 The proportion valvular AF patients prescribed warfarin at hospital discharge 9 10 The valvular AF patients prescribed warfarin at hospital discharge 11 12 Numerator Relevant data elements: 13 Anticoagulation therapy=“Yes”, and warfarin=“Yes” 14 15 Include: 16 Valvular AF patients 17 18 ForRelevant peer data elements: review only 19 20 Atrial arrhythmia type=“valvular atrial fibrillation” 21 Exclude: Denominator 22 ① Contraindication to anticoagulation therapy 23 ② Expire during hospitalization 24 25 Relevant data elements: 26 27 ① Contraindication to anticoagulation therapy=“Yes” 28 ② Expire=“Yes” 29 30 Evaluation time At discharge 31 32 Data sources Case records 33 34 35 Reasons for evaluation

36 NA http://bmjopen.bmj.com/ 37 38 Guidelines 39 ESC 2010 AF guidelines 40 41 Class I 42 Oral anticoagulant therapy (INR 2.0–3.0) is indicated in patients with mitral stenosis and AF 43 (paroxysmal, persistent, or permanent). (Level of Evidence: C)

44 on September 23, 2021 by guest. Protected copyright. 45 Oral anticoagulant therapy (INR 2.0–3.0) is recommended in patients with AF and clinically 46 significant mitral regurgitation. (Level of Evidence: C) 47 48 Ways of reporting 49 Percentages and numerator/denominator 50 51 52 53 54 55 56 57 58 59 60 38

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 74 of 74

1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 Secondary performance measure 8： 6 Proportion of AF patients who are given smoking cessation advice or counseling 7 8 9 The proportion of AF patients with a history of smoking who are given smoking cessation advice 10 or counseling 11 12 The history of smoking refers to that the patients smoked one year before hospitalization. 13 14 The patients with a history of smoking who are given smoking cessation 15 advice or counseling 16 Relevant data elements: 17 Numerator 18 For peerIn the smoking review cessation advice only or counseling, distribution of 19 publicity materials=“Yes”, or making smoking cessation plans with 20 patients/families=“Yes”, or prescription of anti-tobacco remedy 21 22 Include: 23 Patients with a history of smoking 24 25 Relevant data elements: 26 Smoking=“Yes” 27 Denominator 28 Exclude: 29 Expire during hospitalization 30 31 Relevant data elements: 32 Expire=“Yes” 33 34 35 Evaluation time At discharge

36 http://bmjopen.bmj.com/ 37 Data sources Case records 38 39 Reasons for evaluation 40 41 NA 42 Guidelines 43

44 NA on September 23, 2021 by guest. Protected copyright. 45 46 Ways of reporting 47 Percentages and numerator/denominator 48 49 50 51 52 53 54 55 56 57 58 59 60 39

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 75 of 74 BMJ Open

1 2 3 Figure S1. Organizational Framework and Governance of the CCC-AF Program

4 BMJ Open: first published as 10.1136/bmjopen-2017-020968 on 5 July 2018. Downloaded from 5 6 7 8 9 10 11 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 NHFPC, National Health and Family Planning Commission of the People’s Republic of China; 25 26 CHFP, Commission of Health and Family Planning; CSC, Chinese Society of Cardiology; AHA, 27 28 American Heart Association 29 30 31 32 33 34 35

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 23, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 40

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml