10-Year Results from the China PEACE-Retrospective Cathpci Study

Supplementary Online Content

Zheng X, Curtis JP, Hu S, et al; China PEACE Collaborative Group. Coronary catheterization and percutaneous coronary intervention in China: 10-year results from the China PEACE-Retrospective CathPCI Study. JAMA Intern Med. Published online March 14, 2016. doi:10.1001/jamainternmed.2016.0166.

eAppendix 1. China PEACE-Retrospective CathPCI Study Site Investigators and Consultants eMethods. Supplemental Methods eTable 1. Multilevel Logistic Regression Model for In-Hospital Death eTable 2. Multilevel Logistic Regression Model for In-Hospital Death or Treatment Withdrawal eTable 3. Multilevel Logistic Regression Model for Composite End Points eTable 4. Multilevel Logistic Regression Model for Any Bleeding eTable 5. Multilevel Logistic Regression Model for Major Bleeding eTable 6. Multilevel Logistic Regression Model for Access Bleeding eTable 7. Multilevel Logistic Regression Model for Blood Transfusion eTable 8. Demographic, Clinical and Angiographic Characteristics of Patients Undergoing PCI eTable 9. Trends in Percutaneous Coronary Intervention Indication eTable 10. Medications Used During Hospitalization for Patients Undergoing PCI eTable 11. Trends in Percutaneous Coronary Intervention Quality Metrics eTable 12. Unadjusted Rate of Adverse Outcomes of Patients Undergoing Primary PCI eFigure. Study Profile (Flow Chart)

This supplementary material has been provided by the authors to give readers additional information about their work.

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eAppendix 1. China PEACE-Retrospective CathPCI Study Site Investigators and Consultants

Investigators by Hospital Affiliated Hospital of Guiyang Medical College, Lirong Wu, Jiulin Chen; Affiliated Hospital of Hainan Medical College, Tianfa Li, Jun Wang; Affiliated Zhongshan Hospital of Dalian University, Qin Yu, Xiaofei Liu; Changda Hospital of Anshan City, Xiang Jin, Ting Cai; Dalian Municipal Central Hospital, Yongchao Zhi, Lili Sun; Fourth Hospital of Baotou City, Baohong Zhang, Yonghou Yin, Bin Tian; Fourth People's Hospital of Zigong City, Yong Yi, Chaoyong Wu; Fujian Provincial Hospital, Yansong Guo, Xinjing Chen; Fuling Center Hospital of Chongqing City, Liquan Xiang, Lin Ning; General Hospital of the Yangtze River Shipping, Xiuqi Li, Xing’an Wu; Guilin People's Hospital, Wei Zhang, Yanni Zhuang, Hua Lu; Haerbin 242 Hospital, Yin Zhou, Qiuling Hu; Henan Provincial People's Hospital, Chuanyu Gao, Jianghong Zhang, You Zhang; Heze Municipal Hospital, Wentang Niu, Xiaolei Ma, Yong Wang; HGKY Group Company General Hospital, Xiaowen Pan, Yanlong Yan; Hua Xin Hospital, First Hospital of Tsinghua University, Lifu Miao, Yanping Yin, Zhiying Zhang; Huizhou Municipal Central Hospital, Yuansheng Shen, Zhiming Li, Lizhen He; Hunan Province Mawangdui Hospital, Zhiyi Rong, Wei Luo; Ji'an Municipal Central People's Hospital, Xueqiao Wang; Jiangxi Provincial People's Hospital, Qing Huang, Xiaohe Wu; Jilin Integrated Traditional Chinese & Western Medicine Hospital, Jilin Province, Jiangping Shi; Jilin Province People's Hospital, Hui Dai, Yuming Du, Wei Guo; Jingzhou Central Hospital, Xin Li, Qin Xu; Jiuquan City People's Hospital, Yuanfeng Yuan, Zhirong Li; Jixi People's Hospital of the Jixi Municipal People's Hospital Medical Group, Jinbo Gao; Liaoyang Central Hospital, Rihui Liu, Peng Guo; Liaoyuan Central Hospital, Chaoyang Guo, Xiangjun Liu, Rujun Zhao, Zeyong Yu; Longyan First Hospital, Kaihong Chen, Yong Fang, Ying Liao; Nanjing First Hospital, Shaoliang Chen, Haibo Jia, Hongjuan Peng; Nantong Third People's Hospital, Song Chen, Dongya Zhang, Ying Wang; Nanyang Central Hospital, Yudong Li, Jianbu Gao, Shouzhong Yang; Peking University People's Hospital, Chenyang Shen, Yunfeng Liu; Peking University Shenzhen Hospital, Chun Wu, Huan Qu, Saiyong Chen; Qinghai Red Cross Hos, Jianqing Zhang, Chunmei Wei, Yanmei Shen; Quzhou People's Hospital, Xiaoming Tu, Zhenyan Gao; Shangluo Central Hospital, Yingmin Guan, Wenfeng Wang, Ting Xiao; Shangqiu Changzheng People's Hospital, Qian Wang; Shenyang Weikang Hospital, Xujie Fu, Shu Zhang; Shougang Shuicheng Iron & Steel (Group) Co Ltd General Hospital, Min Zhang, Kai Fu, Xiaojing Duan; Shuangshan Hospital of Anshan, Rui Xiao, Ruixia Wu, Bin Li; The Affiliated Hospital of Beihua University, Feng Sun, Qi Zhang; The Fifth People's Hospital of Dalian, Jing Zhang, Yang Zhong; The First Affiliated Hospital of Hebei Northern Institute, Fangjiang Fang, Xiaoyuan Wang; The First Affiliated Hospital of Henan University of Science & Technology, Pingshuan Dong, Laijing Du, Wei Liu; The First Affiliated Hospital of Jia Mu Si University, Zhaofa He, Meihua Jin; The First Hospital of Fuzhou City, Ting Jiang, Zhuoyan Chen; The First Hospital of Xi’an, Manli Cheng, Yuqiang Ji; The First People's Hospital of Guangyuan, Yizhi Pan, Jian Liu; The First People's Hospital of Guangyuan, Tianxun Wang, Ping Yang; The Fourth People's Hospital of Shangqiu shi, Guiyu Huang, Jianjun Pan, Qingliang Cai, Qianying Wang; The General Hospital of Yongzhou, Mingli Lv; The Second Affiliated Hospital of Harbin Medical University, Bo Yu, Yousheng Xu, Zhengqiu Wang; The Second Affiliated Hospital of Kunming Medical University, Jun Shu, Ge Zhang, Kai Li; The Second People's Hospital of Liaoyuan City, Aimin Zhang, Yongfen Kang; Tianjin Medical University General Hospital, Zheng Wan, Bo Bian; Tibet Autonomous Region People's Hospital, Xuejun Hu, Dawa Ciren; Tongchuan Mining Bureau Central Hospital, Guojiong Jia, Jieli Pan; Tongliao City Horqin District First People's Hospital, Junping Fang, Xinli Yu; Ulanqab Central Hospital, Dacheng Wang, Dajun Liu, Xinhong Cao; Wuhai People's Hospital, Zhaohai Zhou, Lei Shi; Wuhu Second People's Hospital, Wuwang Fang, Manxin Chen; Yuanzhou District People's Hospital of Guyuan City, Xiaoping Gao, Meiying Cai, Lining You; Yuncheng Central Hospital, Xuexin Li, Shuqin Li, Yingjia Li.

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Consultants

Paul S. Chan, MD, MSc, Jersey Chen, MD, MPH, David J. Cohen, MD, MSc, Nihar R. Desai, MD, MPH, Kumar Dharmarajan MD, MBA, Mikhail N. Kosiborod, MD, Jing Li, MD, PhD, Xi Li, MD, PhD, Zhenqiu Lin, PhD, Frederick A. Masoudi, MD, MSPH, Jennifer Mattera, DrPH, MPH, Brahmajee K. Nallamothu, MD, MPH, Khurram Nasir, MD, MPH, Sharon-Lise T. Normand, PhD, Joseph S. Ross, MD MHS, John A. Spertus, MD, MPH, Henry H. Ting, MD, Xiao Xu, PhD

St. Luke’s Mid America Heart Institute/University of Missouri Kansas City (PSC, DJC, MNK, JAS), Kansas City, Missouri, United States; Kaiser Permanente (JC), Mid-Atlantic Permanente Research Institute, Rockville, Maryland, United States; Center for Outcomes Research and Evaluation (NRD, KD, ZL, JM, JSR, XX), Yale-New Haven Hospital, New Haven, Connecticut, United States; Division of Cardiology (KD), Department of Internal Medicine, Columbia University Medical Center, New York, New York, United States; State Key Laboratory of Cardiovascular Disease (JL, XL), China Oxford Centre for International Health Research, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Division of Cardiology (FAM), University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States; Veterans Affairs Health Services Research and Development Center of Excellence (BKN), Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, United States; Department of Internal Medicine (BKN) and Center for Healthcare Outcomes and Policy (BKN), University of Michigan, Ann Arbor, Michigan, United States; Research Director, Center for Prevention and Wellness (KN), Baptist Health South Florida, Miami, Florida, United States; Department of Biostatistics (S-LTN), Harvard School of Public Health, Boston, Massachusetts, United States; Department of Health Care Policy (S-LTN), Harvard Medical School, Boston, Massachusetts, United States; Section of General Internal Medicine and the Robert Wood Johnson Clinical Scholars Program (JSR), Department of Internal Medicine, Yale University School of Medicine, Connecticut, United States; Division of Cardiovascular Diseases (HHT) and Knowledge and Evaluation Research Unit (HHT), Mayo Clinic College of Medicine, Rochester, Minnesota. United States; Department of Obstetrics, Gynecology, and Reproductive Sciences (XX), Yale School of Medicine, New Haven, Connecticut, United States

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eMethods. Supplemental Methods

Definitions of Variables

Risk factors (including hypertension, diabetes and dyslipidemia) were defined using documentation in the admission notes, discharge diagnoses, or corroborating laboratory test results.

Estimated glomerular filtration (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease formula.

A successful PCI procedure was defined as the achievement of a minimum intracoronary stenosis diameter reduction to 50% or intra-stent stenosis diameter reduction to 20% in the presence of grade 3 TIMI flow. Procedural success was considered documented if all the required information for its definition could be abstracted from medical chart, including information on residual stenosis and TIMI flow.

Obstructive coronary heart disease was defined as diameter 50% or greater stenosis of the left anterior descending, left circumflex, right coronary artery or left main (LM) coronary artery. Significant stenosis of LM was considered 2-vessel disease, and significant stenosis of LM and right coronary disease was considered 3-vessel disease. Significant stenosis of at least two vessels was considered multi-vessel disease.

Any bleeding was defined as any documented bleeding event or the drop in hemoglobin of≥3 g/dL during hospitalization.

Major bleeding was defined as any intracranial bleeding, absolute hemoglobin decrease of at least 50 g/L, bleeding resulting in hypovolemic shock, or fatal bleeding (bleeding that resulted directly in death within 7 days).

Repeated target vessel revascularization was defined as PCI performed in a vessel treated during the index procedure or any coronary-artery bypass grafting (CABG) procedure performed after the index procedure.

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eMethods. Supplemental Methods

Sampling design

We intended to establish a national-representative sample of hospitals that could perform coronary catheterization and percutaneous coronary intervention (PCI), and a national-representative sample of patients undergoing these procedures in each study year (2001, 2006, and 2011). We used a stratified two-stage random sampling design to achieve that.

First of all, we restricted hospitals to those in urban areas, as coronary catheterization and PCI are rarely performed in rural areas. We considered an area urban if it is part of a downtown or suburban area within a direct-controlled municipality (Beijing, Tianjin, Shanghai, Chongqing) or 1 of 283 prefectural-level cities. Since economic development and medical resources are not identical throughout Mainland China, we separately identified hospitals based on 3 official economic-geographic regions in China, i.e. Eastern, Central and Western (as Central and Western urban regions have similar per capita income and health services capacity, we combined Central and Western regions into 1 stratum, and finally got 2 study strata: Eastern-urban and Central/Western-urban).

In the first stage, we identified hospitals using a simple random sampling procedure within each of the 2 study strata. The sampling framework consisted of the highest-level hospitals in each of the predefined urban regions (833 hospitals in 287 urban regions). Hospital level is officially defined by the Chinese government based on clinical resource capacity. We excluded military hospitals, prison hospitals, specialized hospitals without a cardiovascular disease division, and traditional Chinese medicine hospitals. Since the number of hospitals has remained stable over the past decade, we decided to select representative hospitals from 2011 to reflect current practices and trace this hospital cohort backward to 2006 and 2001 to describe temporal trends.

In the second stage, we drew cases based on the local database of each hospital for patients undergoing coronary catheterization or PCI in each study year. We ordered eligible cases on each hospital’s list by the date of coronary catheterization and selected cases using systematic random sampling with pre specified sample size.

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Weight calculation

Weight of each case, reflecting how many hospitalizations the selected cases could represent, is proportional to the inverse sampling fraction of hospitals within each stratum and the sampling fraction of cases within each hospital to account for differences in the sampling fraction for each time period in all analyses. For example in Eastern-urban stratum, 35 hospitals were sampled from 412 candidate hospitals (the highest-level hospitals in each Eastern urban regions). One hospital refused to participate, 2 hospitals were ineligible for not providing care for cardiovascular diseases, and 32 hospitals got involved. For each of them, the sampling weights is 12.875 (412/32). In one of the sampled hospital (hospital ID is 810), 180 cases were sampled randomly from 982 cases in 2011 (within-hospital weight is 9.093 [982/180], overall weight is 117.072 [12.875*9.093]); 90 cases were sampled randomly from 409 cases in 2006 (within-hospital weight is 4.544 [409/90], overall weight is 58.504 [12.875*4.544]); 90 cases were sampled randomly from 476 cases in 2001 (within-hospital weight is 5.289 [476/90], overall weight is 68.096 [12.875*5.289]).

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eTable 1. Multilevel Logistic Regression Model for In-Hospital Death Predictors Un-weighted Weighted number β S.E. OR 95%CI P number value Tota Outcome Tota Outcome Lower Upper l (%) l (%) Year 2001 407 3(0.74%) 177 1(0.83%) 0 - 1 - - - 2006 1393 18(1.29%) 1142 10(0.89%) 0.5670 0.6842 1.7629 0.4611 6.7400 .41 2011 3660 31(0.85%) 3830 18(0.47%) 0.1401 0.6410 1.1504 0.3275 4.0407 .83 Gender Male 4055 34(0.84%) 3768 19(0.51%) 0 - 1 - - - Female 1405 18(1.28%) 1382 10(0.74%) 0.4284 0.3264 1.5348 0.8094 2.9101 .19 Age <60 2244 11(0.49%) 2118 5(0.21%) 0 - 1 - - - 60-69 1520 12(0.79%) 1459 10(0.68%) 0.4796 0.3948 1.6154 0.7450 3.5024 .22 70-79 1450 21(1.45%) 1321 11(0.8%) 1.0930 0.3966 2.9832 1.3713 6.4898 .006 >=80 246 8(3.25%) 251 4(1.77%) 1.9204 0.4785 6.8235 2.6714 17.4291 <.001 Co-morbidities Hypertension No 2193 23(1.05%) 1997 15(0.76%) 0 - 1 - - - Yes 3267 29(0.89%) 3153 14(0.46%) -0.1684 0.2838 0.8450 0.4845 1.4736 .55 Dyslipidemia No 1773 31(1.75%) 1589 18(1.12%) 0 - 1 - - - Yes 3687 21(0.57%) 3561 12(0.33%) -1.1335 0.2977 0.3219 0.1796 0.5769 <.001 Diabetes No 4064 36(0.89%) 3790 22(0.57%) 0 - 1 - - - Yes 1396 16(1.15%) 1359 8(0.57%) 0.2603 0.3507 1.2973 0.6525 2.5793 .46 Current smoking No 3535 37(1.05%) 3290 21(0.63%) 0 - 1 - - - Yes 1925 15(0.78%) 1859 9(0.48%) -0.2978 0.2920 0.7425 0.4189 1.3160 .31 Prior MI No 3983 40(1.00%) 3745 22(0.60%) 0 - 1 - - - Yes 1477 12(0.81%) 1405 7(0.51%) -0.2139 0.2512 0.8074 0.4935 1.3210 .39 Prior PCI No 4985 52(1.04%) 4671 29(0.63%) 0 - 1 - - - Yes 475 0(0.00%) 479 0(0.00%) -22.812 . 0.0000 . . . 9 Prior CABG No 5443 52(0.96%) 5127 29(0.57%) 0 - 1 - - - Yes 17 0(0.00%) 22 0(0.00%) -19.724 . 0.0000 . . . 1 Prior stroke No 5099 43(0.84%) 4806 25(0.53%) 0 - 1 - - - Yes 361 9(2.49%) 344 4(1.19%) 1.1007 0.3987 3.0063 1.3762 6.5673 .006

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CABG: coronary artery bypass graft; CAD: coronary artery disease; eGFR: estimated glomerular filtration rate; MI: myocardial infarction; NSTEMI: non ST-segment elevation myocardial infarction; PCI: percutaneous coronary Presentations at admission eGFR < 60 No 4790 34(0.71%) 4558 18(0.41%) 0 - 1 - - - Yes 670 18(2.69%) 591 11(1.86%) 1.3511 0.3145 3.8618 2.085 7.1527 <.001 eGFR unmeasured No 4943 46(0.93%) 4715 27(0.58%) 0 - 1 - - - Yes 517 6(1.16%) 434 2(0.51%) 0.2231 0.4902 1.2500 0.4783 3.2668 .65 Heart failure No 5294 50(0.94%) 5000 29(0.57%) 0 - 1 - - - Yes 166 2(1.20%) 149 1(0.52%) 0.2461 0.7023 1.2790 0.3229 5.0660 .73 Cardiogenic shock No 5404 49(0.91%) 5106 28(0.54%) 0.0000 - 1 - - - Yes 56 3(5.36%) 43 2(3.92%) 1.8223 0.6503 6.1860 1.7293 22.1279 .005 Cardiac arrest No 5458 52(0.95%) 5148 29(0.57%) 0.0000 - 1 - - - Yes 2 0(0.00%) 1 0(0.00%) -17.7213 . 0.0000 . . . Discharge diagnosis STEMI No 3304 10(0.30%) 3288 7(0.21%) 0 - 1 - - - Yes 2156 42(1.95%) 1861 23(1.22%) 1.8786 0.3513 6.5444 3.2871 13.0295 <.001 intervention; STEMI: ST-segment elevation myocardial infarction. Intra-class correlation coefficient=0.1955. S.E.: standard error; OR: odds ratio, CI: confidence interval.

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eTable 2. Multilevel Logistic Regression Model for In-Hospital Death or Treatment Withdrawal Predictors Un-weighted Weighted number β S.E. OR 95%CI P number value Total Outcome Total Outcome Lower Upper (%) (%) Year 2001 407 4(0.98%) 177 2(1.00%) 0 - 1 - - - 2006 1393 19(1.36%) 1142 11(0.96%) 0.3316 0.5709 1.3932 0.4551 4.2651 .56 2011 3660 35(0.96%) 3830 23(0.59%) -0.0276 0.5247 0.9728 0.3478 2.7204 .96 Gender Male 4055 38(0.94%) 3768 22(0.59%) 0 - 1 - - - Female 1405 20(1.42%) 1382 13(0.94%) 0.4230 0.3091 1.5265 0.8329 2.7976 .17 Age <60 2244 14(0.62%) 2118 7(0.35%) 0 - 1 - - - 60-69 1520 12(0.79%) 1459 10(0.68%) 0.2371 0.3630 1.2675 0.6223 2.5818 .51 70-79 1450 23(1.59%) 1321 12(0.87%) 0.9429 0.3626 2.5673 1.2614 5.2254 .009 >=80 246 9(3.66%) 251 7(2.68%) 1.7999 0.4231 6.0488 2.6395 13.862 <.001 Co-morbidities Hypertension No 2193 26(1.19%) 1997 18(0.90%) 0 - 1 - - - Yes 3267 32(0.98%) 3153 18(0.56%) -0.1930 0.2789 0.8244 0.4772 1.4242 .49 Dyslipidemia No 1773 35(1.97%) 1589 21(1.34%) 0 - 1 - - - Yes 3687 23(0.62%) 3561 14(0.40%) -1.1657 0.2882 0.3117 0.1772 0.5484 <.001

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Diabetes No 4064 41(1.01%) 3790 27(0.72%) 0 - 1 - - - Yes 1396 17(1.22%) 1359 8(0.60%) 0.1903 0.3302 1.2096 0.6333 2.3106 .56 Current smoking No 3535 42(1.19%) 3290 26(0.80%) 0 - 1 - - - Yes 1925 16(0.83%) 1859 9(0.49%) -0.3609 0.2817 0.6970 0.4013 1.2106 .20 Prior MI No 3983 43(1.08%) 3745 26(0.69%) 0 - 1 - - - Yes 1477 15(1.02%) 1405 10(0.68%) -0.0618 0.2375 0.9401 0.5902 1.4974 .79 Prior PCI No 4985 58(1.16%) 4671 35(0.76%) 0 - 1 - - - Yes 475 0(0%) 479 0(0%) -22.9233 . 0.0000 . . . Prior CABG No 5443 58(1.07%) 5127 35(0.69%) 0 - 1 - - - Yes 17 0(0.00%) 22 0(0.00%) -19.8344 . 0.0000 . . . Prior stroke No 5099 48(0.94%) 4806 29(0.6%) 0 - 1 - - - Yes 361 10(2.77%) 344 6(1.85%) 1.0979 0.3712 2.9980 1.4483 6.2060 .003 Presentations at admission eGFR <60 No 4790 40(0.84%) 4558 24(0.54%) 0 - 1 - - - Yes 670 18(2.69%) 591 11(1.86%) 1.1873 0.3091 3.2784 1.7888 6.0085 <.001

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eGFR unmeasured No 4943 51(1.03%) 4715 33(0.69%) 0 - 1 - - - Yes 517 7(1.35%) 434 3(0.62%) 0.2750 0.4582 1.3166 0.5363 3.2318 .55 Heart failure No 5294 56(1.06%) 5000 35(0.69%) 0 - 1 - - - Yes 166 2(1.20%) 149 1(0.52%) 0.1316 0.6999 1.1407 0.2894 4.4967 .85 Cardiogenic shock No 5404 53(0.98%) 5106 31(0.61%) 0 - 1 - - - Yes 56 5(8.93%) 43 4(9.62%) 2.2924 0.4196 9.8983 4.3494 22.526 <.001 Cardiac arrest No 5458 58(1.06%) 5148 35(0.69%) 0 - 1 - - - Yes 2 0(0.00%) 1 0(0.00%) -17.8316 . 0.0000 . . . Discharge diagnosis STEMI No 3304 11(0.33%) 3288 7(0.21%) 0 - 1 - - - Yes 2156 47(2.18%) 1861 28(1.52%) 1.8978 0.3235 6.6715 3.5386 12.5781 <.001 CABG: coronary artery bypass graft; CAD: coronary artery disease; eGFR: estimated glomerular filtration rate; MI: myocardial infarction; NSTEMI: non ST-segment elevation myocardial infarction; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction. Intra-class correlation coefficient=0.1259. S.E.: standard error; OR: odds ratio, CI: confidence interval.

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eTable 3. Multilevel Logistic Regression Model for Composite End Points Predictors Un-weighted Weighted number β S.E. OR 95%CI P number value Total Outcome Total Outcome Lower Upper (%) (%) Year 2001 407 13(3.19%) 177 5(2.72%) 0 - 1 - - - 2006 1393 60(4.31%) 1142 42(3.72%) 0.3106 0.3686 1.3642 0.6624 2.8097 .40 2011 3660 191(5.22%) 3830 169(4.42%) 0.5121 0.3887 1.6687 0.7790 3.5748 .19 Gender Male 4055 197(4.86%) 3768 170(4.50%) 0 - 1 - - - Female 1405 67(4.77%) 1382 47(3.40%) -0.0195 0.1807 0.9807 0.6882 1.3974 .91 Age <60 2244 79(3.52%) 2118 72(3.41%) 0 - 1 - - - 60-69 1520 78(5.13%) 1459 67(4.60%) 0.3937 0.1443 1.4824 1.1173 1.9668 .006 70-79 1450 87(6.00%) 1321 63(4.76%) 0.5592 0.1174 1.7493 1.3896 2.2020 <.001 >=80 246 20(8.13%) 251 14(5.66%) 0.8859 0.2546 2.4252 1.4725 3.9945 <.001 Co-morbidities Hypertension No 2193 91(4.15%) 1997 62(3.10%) 0 - 1 - - - Yes 3267 173(5.30%) 3153 155(4.90%) 0.2559 0.1260 1.2916 1.0089 1.6535 .04 Dyslipidemia No 1773 101(5.70%) 1589 80(5.04%) 0 - 1 - - - Yes 3687 163(4.42%) 3561 137(3.83%) -0.2669 0.1462 0.7657 0.5750 1.0197 .07

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Diabetes No 4064 191(4.70%) 3790 157(4.15%) 0 - 1 - - - Yes 1396 73(5.23%) 1359 59(4.36%) 0.1123 0.1497 1.1189 0.8343 1.5005 .45 Current smoking No 3535 172(4.87%) 3290 125(3.81%) 0 - 1 - - - Yes 1925 92(4.78%) 1859 91(4.91%) -0.0188 0.1595 0.9813 0.7179 1.3415 .91 Prior MI No 3983 198(4.97%) 3745 164(4.39%) 0 - 1 - - - Yes 1477 66(4.47%) 1405 52(3.72%) -0.1119 0.1481 0.8942 0.6688 1.1954 .45 Prior PCI No 4985 235(4.71%) 4671 188(4.03%) 0 - 1 - - - Yes 475 29(6.11%) 479 28(5.91%) 0.2733 0.2363 1.3143 0.8271 2.0883 .25 Prior CABG No 5443 264(4.85%) 5127 217(4.22%) 0 - 1 - - - Yes 17 0(0.00%) 22 0(0.00%) -21.388 . 0.0000 . . . 9 Prior stroke No 5099 199(3.9%) 4806 162(3.36%) 0 - 1 - - - Yes 361 65(18.01%) 344 55(15.99%) 1.6877 0.2147 5.4071 3.5497 8.2364 <.001 Presentations at admission eGFR <60 No 4790 220(4.59%) 4558 186(4.08%) 0 - 1 - - - Yes 670 44(6.57%) 591 30(5.15%) 0.3785 0.1678 1.4601 1.0509 2.0285 .02

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eGFR unmeasured No 4943 246(4.98%) 4715 201(4.26%) 0 - 1 - - - Yes 517 18(3.48%) 434 15(3.56%) -0.3729 0.2617 0.6887 0.4123 1.1504 .15 Heart failure No 5294 254(4.8%) 5000 208(4.16%) 0 - 1 - - - Yes 166 10(6.02%) 149 8(5.59%) 0.2406 0.3496 1.2720 0.641 2.5238 .49 Cardiogenic shock No 5404 258(4.77%) 5106 211(4.14%) 0 - 1 - - - Yes 56 6(10.71%) 43 5(11.94%) 0.8728 0.3573 2.3935 1.1882 4.8214 .01 Cardiac arrest No 5458 263(4.82%) 5148 216(4.19%) 0 - 1 - - - Yes 2 1(50.00%) 1 1(67.90%) 2.9833 1.3966 19.7529 1.2788 305.09 .03 85 Discharge diagnosis STEMI No 3304 129(3.90%) 3288 116(3.51%) 0 - 1 - - - Yes 2156 135(6.26%) 1861 101(5.43%) 0.4972 0.1567 1.6441 1.2092 2.2353 .002 CABG: coronary artery bypass graft; CAD: coronary artery disease; eGFR: estimated glomerular filtration rate; MI: myocardial infarction; NSTEMI: non ST-segment elevation myocardial infarction; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction. Intra-class correlation coefficient=0.0746. S.E.: standard error; OR: odds ratio, CI: confidence interval.

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eTable 4. Multilevel Logistic Regression Model for Any Bleeding Predictors Un-weighted Weighted number β S.E. OR 95%CI P number value Total Outcome Total Outcome Lower Upper (%) (%) Year 2001 407 52(12.78%) 177 22(12.37%) 0 - 1 - - - 2006 1393 142(10.19%) 1142 121(10.64%) -0.255 0.1889 0.7749 0.5351 1.1222 .18 2011 3660 300(8.20%) 3830 296(7.73%) -0.495 0.2122 0.6095 0.4021 0.9239 .02 Gender Male 4055 349(8.61%) 3768 293(7.78%) 0 - 1 - - - Female 1405 145(10.32%) 1382 146(10.59%) 0.2005 0.1131 1.222 0.9791 1.5253 .08 Age <60 2244 151(6.73%) 2118 131(6.20%) 0 - 1 - - - 60-69 1520 135(8.88%) 1459 126(8.64%) 0.3009 0.1029 1.3511 1.1043 1.653 .004 70-79 1450 166(11.45%) 1321 134(10.16%) 0.5833 0.0875 1.7920 1.5096 2.1271 <.001 >=80 246 42(17.07%) 251 48(19.09%) 1.0486 0.1949 2.8537 1.9475 4.1815 <.001 Co-morbidities Hypertension No 2193 166(7.57%) 1997 138(6.91%) 0 - 1 - - - Yes 3267 328(10.04%) 3153 301(9.56%) 0.3095 0.0939 1.3628 1.1336 1.6383 .001 Dyslipidemia No 1773 153(8.63%) 1589 135(8.52%) 0 - 1 - - - Yes 3687 341(9.25%) 3561 304(8.54%) 0.0761 0.0913 1.0791 0.9023 1.2904 .40 Diabetes No 4064 361(8.88%) 3790 315(8.32%) 0 - 1 - - - Yes 1396 133(9.53%) 1359 124(9.11%) 0.0771 0.1337 1.0802 0.8312 1.4038 .56 Current smoking No 3535 322(9.11%) 3290 286(8.71%) 0 - 1 - - - Yes 1925 172(8.94%) 1859 153(8.23%) -0.0212 0.1103 0.9790 0.7888 1.2152 .85 Prior MI No 3983 343(8.61%) 3745 308(8.22%) 0 - 1 - - - Yes 1477 151(10.22%) 1405 131(9.36%) 0.1894 0.1153 1.2085 0.964 1.5150 .10 Prior PCI No 4985 466(9.35%) 4671 414(8.86%) 0 - 1 - - - Yes 475 28(5.89%) 479 26(5.36%) -0.4985 0.1674 0.6074 0.4375 0.8434 .003 Prior CABG No 5443 494(9.08%) 5127 439(8.57%) 0 - 1 - - - Yes 17 0(0.00%) 22 0(0.00%) -22.0609 . 0 . . . Prior stroke No 5099 465(9.12%) 4806 413(8.6%) 0 - 1 - - - Yes 361 29(8.03%) 344 26(7.61%) -0.1387 0.1970 0.8705 0.5916 1.2808 .48 Presentations at admission

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eGFR <60 No 4790 386(8.06%) 4558 351(7.71%) 0 - 1 - - - Yes 670 108(16.12%) 591 88(14.87%) 0.7851 0.1442 2.1925 1.6527 2.9087 <.001 eGFR unmeasured No 4943 464(9.39%) 4715 418(8.87%) 0 - 1 - - - Yes 517 30(5.80%) 434 21(4.89%) -0.5198 0.2437 0.5946 0.3688 0.9588 .03

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Heart failure No 5294 480(9.07%) 5000 432(8.64%) 0 - 1 - - - Yes 166 14(8.43%) 149 7(5.00%) -0.0793 0.2709 0.9237 0.5432 1.5709 .77 Cardiogenic shock No 5404 479(8.86%) 5106 423(8.28%) 0 - 1 - - - Yes 56 15(26.79%) 43 16(37.95%) 1.3249 0.3140 3.7616 2.0328 6.9609 <.001 Cardiac arrest No 5458 494(9.05%) 5148 439(8.53%) 0 - 1 - - - Yes 2 0(0.00%) 1 0(0.00%) -19.0579 . 0.0000 . . . Discharge diagnosis STEMI No 3304 251(7.60%) 3288 226(6.88%) 0 - 1 - - - Yes 2156 243(11.27%) 1861 213(11.45%) 0.4351 0.0908 1.5451 1.2932 1.8460 <.001 CABG: coronary artery bypass graft; CAD: coronary artery disease; eGFR: estimated glomerular filtration rate; MI: myocardial infarction; NSTEMI: non ST-segment elevation myocardial infarction; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction. Intra-class correlation coefficient=0.0724 S.E.: standard error; OR: odds ratio, CI: confidence interval.

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eTable 5. Multilevel Logistic Regression Model for Major Bleeding Predictors Un-weighted Weighted number β S.E. OR 95%CI P number value Total Outcome Total Outcome Lower Upper (%) (%) Year 2001 407 5(1.23%) 177 2(1.09%) 0 - 1 - - - 2006 1393 14(1.01%) 1142 12(1.02%) -0.2030 0.5494 0.8162 0.2781 2.3958 .71 2011 3660 27(0.74%) 3830 35(0.92%) -0.5150 0.5056 0.5975 0.2218 1.6095 .31 Gender Male 4055 34(0.84%) 3768 37(0.98%) 0 - 1 - - - Female 1405 12(0.85%) 1382 12(0.87%) 0.0186 0.3737 1.0188 0.4898 2.1191 .96 Age <60 2244 12(0.53%) 2118 14(0.68%) 0 - 1 - - - 60-69 1520 14(0.92%) 1459 10(0.67%) 0.5476 0.3792 1.7291 0.8223 3.6359 .15 70-79 1450 15(1.03%) 1321 15(1.13%) 0.6649 0.3309 1.9443 1.0164 3.7193 .04 >=80 246 5(2.03%) 251 10(3.97%) 1.3504 0.4736 3.8589 1.5252 9.7633 .004 Co-morbidities Hypertension No 2193 19(0.87%) 1997 18(0.91%) 0 - 1 - - - Yes 3267 27(0.83%) 3153 31(0.98%) -0.0476 0.2530 0.9535 0.5808 1.5654 .85 Dyslipidemia No 1773 17(0.96%) 1589 17(1.08%) 0 - 1 - - - Yes 3687 29(0.79%) 3561 32(0.90%) -0.1998 0.2673 0.8189 0.4850 1.3828 .45

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Diabetes No 4064 38(0.94%) 3790 46(1.21%) 0 - 1 - - - Yes 1396 8(0.57%) 1359 3(0.24%) -0.4932 0.4148 0.6106 0.2709 1.3767 .23 Current smoking No 3535 25(0.71%) 3290 25(0.77%) 0 - 1 - - - Yes 1925 21(1.09%) 1859 24(1.28%) 0.4373 0.2919 1.5485 0.8739 2.7441 .13 Prior MI No 3983 31(0.78%) 3745 32(0.84%) 0 - 1 - - - Yes 1477 15(1.02%) 1405 17(1.24%) 0.2685 0.3459 1.3080 0.6640 2.5766 .44 Prior PCI No 4985 43(0.86%) 4671 47(1.01%) 0 - 1 - - - Yes 475 3(0.63%) 479 2(0.37%) -0.3140 0.5660 0.7305 0.2409 2.2152 .58 Prior CABG No 5443 46(0.85%) 5127 49(0.96%) 0 - 1 - - - Yes 17 0(0.00%) 22 0(0.00%) -19.6004 . 0 . . . Prior stroke No 5099 41(0.80%) 4806 44(0.92%) 0 - 1 - - - Yes 361 5(1.39%) 344 5(1.40%) 0.5497 0.3843 1.7327 0.8158 3.6799 .15 Presentations at admission eGFR <60 No 4790 35(0.73%) 4558 37(0.82%) 0 - 1 - - - Yes 670 11(1.64%) 591 12(1.97%) 0.8188 0.2249 2.2677 1.4592 3.5242 <.001

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eGFR unmeasured No 4943 44(0.89%) 4715 48(1.02%) 0 - 1 - - - Yes 517 2(0.39%) 434 1(0.19%) -0.8384 0.7028 0.4324 0.1090 1.7145 .23 Heart failure No 5294 43(0.81%) 5000 48(0.96%) 0 - 1 - - - Yes 166 3(1.81%) 149 1(0.71%) 0.8098 0.5602 2.2475 0.7496 6.7385 .15 Cardiogenic shock No 5404 43(0.80%) 5106 44(0.87%) 0 - 1 - - - Yes 56 3(5.36%) 43 5(11.05%) 1.9540 0.5388 7.0570 2.4547 20.2881 <.001 Cardiac arrest No 5458 46(0.84%) 5148 49(0.95%) 0 - 1 - - - Yes 2 0(0.00%) 1 0(0.00%) -17.5976 . 0.0000 . . . Discharge diagnosis STEMI No 3304 21(0.64%) 3288 25(0.75%) 0 - 1 - - - Yes 2156 25(1.16%) 1861 24(1.30%) 0.6065 0.253 1.8340 1.1171 3.0112 .02 CABG: coronary artery bypass graft; CAD: coronary artery disease; eGFR: estimated glomerular filtration rate; MI: myocardial infarction; NSTEMI: non ST-segment elevation myocardial infarction; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction. Intra-class correlation coefficient=0.1761 S.E.: standard error; OR: odds ratio, CI: confidence interval.

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eTable 6. Multilevel Logistic Regression Model for Access Bleeding Predictors Un-weighted Weighted number β S.E. OR 95%CI P number value Total Outcome Total Outcome Lower Upper (%) (%) Year 2001 407 21(5.16%) 177 8(4.79%) 0 - 1 - - - 2006 1393 62(4.45%) 1142 54(4.76%) -0.1552 0.2932 0.8562 0.482 1.5211 0.60 2011 3660 62(1.69%) 3830 51(1.32%) -1.1497 0.3053 0.3167 0.1741 0.5762 <.001 Gender Male 4055 96(2.37%) 3768 67(1.78%) 0 - 1 - - - Female 1405 49(3.49%) 1382 47(3.38%) 0.3989 0.1873 1.4902 1.0324 2.1512 0.03 Age <60 2244 43(1.92%) 2118 31(1.45%) 0 - 1 - - - 60-69 1520 34(2.24%) 1459 35(2.39%) 0.158 0.2124 1.1711 0.7724 1.7757 0.46 70-79 1450 56(3.86%) 1321 39(2.98%) 0.7209 0.1466 2.0563 1.5428 2.7406 <.001 >=80 246 12(4.88%) 251 9(3.44%) 0.9651 0.2531 2.6249 1.5984 4.3106 <.001 Co-morbidities Hypertension No 2193 52(2.37%) 1997 43(2.14%) 0 - 1 - - - Yes 3267 93(2.85%) 3153 71(2.25%) 0.1876 0.1886 1.2064 0.8336 1.7458 0.32 Dyslipidemia No 1773 44(2.48%) 1589 39(2.44%) 0 - 1 - - - Yes 3687 101(2.74%) 3561 75(2.1%) 0.1014 0.1575 1.1068 0.8129 1.5069 0.52

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Diabetes No 4064 103(2.53%) 3790 79(2.09%) 0 - 1 - - - Yes 1396 42(3.01%) 1359 34(2.53%) 0.1764 0.2162 1.1929 0.7808 1.8225 0.41 Current smoking No 3535 108(3.06%) 3290 90(2.75%) 0 - 1 - - - Yes 1925 37(1.92%) 1859 23(1.25%) -0.475 0.2195 0.6219 0.4044 0.9562 0.03 Prior MI No 3983 98(2.46%) 3745 79(2.11%) 0 - 1 - - - Yes 1477 47(3.18%) 1405 35(2.46%) 0.2646 0.2217 1.3029 0.8438 2.012 0.23 Prior PCI No 4985 137(2.75%) 4671 106(2.26%) 0 - 1 - - - Yes 475 8(1.68%) 479 8(1.66%) -0.5005 0.3328 0.6062 0.3157 1.1639 0.13 Prior CABG No 5443 145(2.66%) 5127 114(2.22%) 0 - 1 - - - Yes 17 0(0%) 22 0(0%) -20.767 . 0 . . . Prior stroke No 5099 134(2.63%) 4806 107(2.23%) 0 - 1 - - - Yes 361 11(3.05%) 344 6(1.85%) 0.1523 0.4269 1.1645 0.5044 2.6886 0.72 Presentations at admission eGFR <60 No 4790 118(2.46%) 4558 94(2.07%) 0 - 1 - - - Yes 670 27(4.03%) 591 19(3.24%) 0.5084 0.247 1.6625 1.0246 2.6976 0.04

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eGFR unmeasured No 4943 134(2.71%) 4715 106(2.24%) 0 - 1 - - - Yes 517 11(2.13%) 434 8(1.84%) -0.2482 0.3111 0.7802 0.424 1.4355 0.42 Heart failure No 5294 143(2.7%) 5000 112(2.24%) 0 - 1 - - - Yes 166 2(1.2%) 149 2(1.07%) -0.8226 0.639 0.4393 0.1256 1.5368 0.20 Cardiogenic shock No 5404 142(2.63%) 5106 112(2.19%) 0 - 1 - - - Yes 56 3(5.36%) 43 2(3.84%) 0.7408 0.5746 2.0975 0.6802 6.4685 0.20 Cardiac arrest No 5458 145(2.66%) 5148 114(2.21%) 0 - 1 - - - Yes 2 0(0%) 1 0(0%) -17.7641 . 0 . . . Discharge diagnosis STEMI No 3304 87(2.63%) 3288 70(2.13%) 0 - 1 - - - Yes 2156 58(2.69%) 1861 44(2.34%) 0.022 0.1836 1.0222 0.7133 1.4649 0.90 CABG: coronary artery bypass graft; CAD: coronary artery disease; eGFR: estimated glomerular filtration rate; MI: myocardial infarction; NSTEMI: non ST-segment elevation myocardial infarction; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction. Intra-class correlation coefficient=0.0742 S.E.: standard error; OR: odds ratio, CI: confidence interval

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eTable 7. Multilevel Logistic Regression Model for Blood Transfusion Predictors Un-weighted Weighted β S.E. OR 95%CI P number number value Total Outcome Total Outcome Lower Upper (%) (%) Year 2001 407 3(0.74%) 177 2(1.16%) 0 - 1 - - - 2006 1393 17(1.22%) 1142 14(1.24%) 0.5091 0.5541 1.6638 0.5616 4.9286 .36 2011 3660 36(0.98%) 3830 34(0.89%) 0.2910 0.5622 1.3377 0.4445 4.0261 .60 Gender Male 4055 35(0.86%) 3768 27(0.71%) 0 - 1 - - - Female 1405 21(1.49%) 1382 24(1.7%) 0.5555 0.3691 1.7428 0.8454 3.5929 .13 Age <60 2244 9(0.40%) 2118 8(0.39%) 0 - 1 - - - 60-69 1520 14(0.92%) 1459 12(0.85%) 0.8366 0.3565 2.3085 1.1478 4.6433 .02 70-79 1450 26(1.79%) 1321 23(1.76%) 1.5116 0.3380 4.5342 2.3376 8.7949 <.001 >=80 246 7(2.85%) 251 6(2.53%) 1.9842 0.4607 7.2734 2.9484 17.9428 <.001 Co-morbidities Hypertension No 2193 22(1.00%) 1997 20(0.99%) 0 - 1 - - - Yes 3267 34(1.04%) 3153 31(0.97%) 0.0371 0.2425 1.0378 0.6452 1.6694 .88 Dyslipidemia No 1773 18(1.02%) 1589 18(1.11%) 0 - 1 - - - Yes 3687 38(1.03%) 3561 33(0.92%) 0.0152 0.2744 1.0153 0.5930 1.7386 .96 Diabetes No 4064 35(0.86%) 3790 32(0.85%) 0 - 1 - - - Yes 1396 21(1.50%) 1359 18(1.33%) 0.5642 0.2695 1.7581 1.0368 2.9813 .04

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Current smoking No 3535 48(1.36%) 3290 44(1.35%) 0 - 1 - - - Yes 1925 8(0.42%) 1859 6(0.32%) -1.1935 0.3296 0.3032 0.1589 0.5784 <.001 Prior MI No 3983 40(1.00%) 3745 36(0.96%) 0 - 1 - - - Yes 1477 16(1.08%) 1405 15(1.03%) 0.0765 0.2936 1.0795 0.6072 1.9192 .79 Prior PCI No 4985 55(1.10%) 4671 50(1.07%) 0 - 1 - - - Yes 475 1(0.21%) 479 0(0.09%) -1.6654 0.9786 0.1891 0.0278 1.2874 .09 Prior CABG No 5443 56(1.03%) 5127 50(0.98%) 0 - 1 - - - Yes 17 0(0%) 22 0(0.00%) -19.7989 . 0 . . . Prior stroke No 5099 52(1.02%) 4806 47(0.98%) 0 - 1 - - - Yes 361 4(1.11%) 344 3(0.94%) 0.0839 0.7042 1.0875 0.2735 4.3237 .91 Presentations at admission eGFR <60 No 4790 32(0.67%) 4558 26(0.57%) 0 - 1 - - - Yes 670 24(3.58%) 591 24(4.10%) 1.7091 0.3303 5.5240 2.8911 10.5546 <.001 eGFR unmeasured No 4943 55(1.11%) 4715 50(1.05%) 0 - 1 - - - Yes 517 1(0.19%) 434 1(0.17%) -1.7589 0.8988 0.1722 0.0296 1.0027 .05

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Heart failure No 5294 54(1.02%) 5000 50(0.99%) 0 - 1 - - - Yes 166 2(1.20%) 149 1(0.48%) 0.1684 0.6664 1.1834 0.3205 4.3687 .80 Cardiogenic shock No 5404 53(0.98%) 5106 47(0.92%) 0 - 1 - - - Yes 56 3(5.36%) 43 4(8.41%) 1.7431 0.6193 5.7148 1.6978 19.2363 .005 Cardiac arrest No 5458 56(1.03%) 5148 50(0.98%) 0 - 1 - - - Yes 2 0(0.00%) 1 0(0.00%) -17.7962 . 0.0000 . . . Discharge diagnosis STEMI No 3304 24(0.73%) 3288 22(0.68%) 0 - 1 - - - Yes 2156 32(1.48%) 1861 28(1.51%) 0.7222 0.3245 2.0590 1.0900 3.8896 .03 CABG: coronary artery bypass graft; CAD: coronary artery disease; eGFR: estimated glomerular filtration rate; MI: myocardial infarction; NSTEMI: non ST-segment elevation myocardial infarction; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction. Intra-class correlation coefficient=0·0859 S.E.: standard error; OR: odds ratio, CI: confidence interval

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eTable 8. Demographic, Clinical and Angiographic Characteristics of Patients Undergoing PCI

2001 (n=407) 2006 (n=1393) 2011 (n=3660) P n Weighted % n Weighted % n Weighted % trend Demographics Female 94 23.1(19.0-27.1) 306 22.7(20.5-24.9) 1005 28.2(26.8-29.7) <.001 Age(years) 60(51, 67) 62(53, 70) 62(55, 71) <.001 <60 189 46.6(41.8-51.5) 579 42.6(40.1-45.2) 1476 40.4(38.8-42.0) .010 60-69 147 34(29.4-38.6) 421 31.1(28.6-33.5) 1110 31.8(30.3-33.3) .68 70-79 67 17.9(14.2-21.7) 360 23.4(21.2-25.6) 929 23.8(22.4-25.2) .03 ≥80 4 1.4(0.3-2.6) 33 2.9(2.0-3.8) 145 4.0(3.3-4.6) .002 Co-morbidities Hypertension 218 51.8(46.9-56.6) 791 61.3(58.8-63.9) 2258 61.6(60.0-63.2) .003 Dyslipidemia 242 59.1(54.3-63.8) 919 67.8(65.3-70.2) 2526 70.0(68.5-71.5) <.001 Diabetes 71 17.3(13.6-21.0) 343 25.1(22.8-27.4) 982 27.2(25.8-28.6) <.001 Current smoker 147 38.6(33.8-43.3) 496 36.2(33.7-38.7) 1282 36(34.4-37.5) .39 Prior MI 125 34.5(29.8-39.1) 400 30.4(27.9-32.8) 952 26(24.6-27.5) <.001 Prior PCI 17 5.0(2.9-7.2) 89 7.3(5.9-8.6) 369 10.1(9.1-11.1) <.001 Prior CABG 3 0.6(0.0-1.4) 2 0.1(0.0-0.3) 12 0.5(0.3-0.7) .39 Prior stroke 25 7.2(4.7-9.7) 85 6.5(5.2-7.7) 251 6.7(5.9-7.5) .94

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Presentations at admission eGFR (mL/min 77.9(64.1, 81.2(66.5, 90.1(73.4, <.001 per1.73m2) 94.6) 98.0) 107.0)

eGFR<60 65 16.2(12.6-19.8) 208 14.2(12.4-16.1) 397 10.4(9.5-11.4) <.001 eGFR≥60 245 62.2(57.5-66.9) 1017 74.2(71.9-76.5) 3011 82.7(81.4-83.9) <.001 eGFR 97 21.5(17.5-25.5) 168 11.6(9.9-13.2) 252 6.9(6.1-7.7) <.001 unmeasured Heart failure at 16 3.4(1.7-5.2) 47 4.0(3.0-5.1) 103 2.5(2.0-3.0) .02 admission Cardiogenic shock 5 0.8(0.0-1.7) 15 0.7(0.3-1.2) 36 0.9(0.6-1.2) .73 at admission Cardiac arrest at 0 0(0.0-0.0) 1 0(0.0-0.1) 1 0(0.0-0.1) .96 admission Extent of CAD (%) Non-obstructive 2 0.3(0.0-0.9) 1 0(0.0-0.1) 5 0.2(0.0-0.3) .91 CAD (<50%) 1-vessel disease 162 37.7(33.0-42.4) 436 30.6(28.1-33.0) 1033 27.4(26.0-28.9) <.001 2-vessel disease 150 38.4(33.7-43.1) 522 38.7(36.2-41.3) 1376 38.0(36.4-39.5) .67 3-vessel disease 87 22.6(18.5-26.6) 428 30.5(28.1-32.9) 1236 34.2(32.6-35.7) <.001 Left main disease 6 1.6(0.4-2.8) 60 3.9(2.9-4.9) 214 7.3(6.4-8.1) <.001 CABG: coronary artery bypass graft; CAD: coronary artery disease; eGFR: estimated glomerular filtration rate; MI: myocardial infarction; NSTEMI: non ST-segment elevation myocardial infarction; STEMI: ST-segment elevation myocardial infarction.

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eTable 9. Trends in Percutaneous Coronary Intervention Indication

2001(n=407) 2006 (n=1393) 2011 (n=3660) P Relative Weighted % Relative Weighted % Relative Weighted % trend frequency (95%CI) frequency (95%CI) frequency (95%CI) PCI for STEMI 164/407 40.1(35.3‐44.9) 618/1393 40.1(37.5‐42.7) 1374/3660 34.8(33.2‐36.3) <.001 Primary PCI for 45/164 30.7(23.6‐37.7) 181/618 28.2(24.6‐31.7) 409/1374 27.8(25.5‐30.2) .51 STEMI PCI after fibrinolytic 45/164 22.5(16.1‐28.8) 123/618 16.3(13.4‐19.3) 164/1374 10.1(8.5‐11.6) <.001 therapy Late reperfusion* 74/164 46.9(39.2‐54.5) 314/618 55.5(51.6‐59.4) 801/1374 62.1(59.6‐64.7) <.001 PCI for NSTEMI 11/407 2.8(1.2‐4.4) 72/1393 5.1(4.0‐6.3) 312/3660 8.1(7.2‐8.9) <.001 PCI for UA 119/407 32.8(28.3‐37.4) 444/1393 38.1(35.5‐40.6) 1368/3660 41.8(40.2‐43.4) <.001 PCI for Stable CAD 112/407 24.1(19.9‐28.2) 257/1393 16.6(14.6‐18.5) 603/3660 15.2(14.1‐16.4) <.001 ACS: acute coronary syndrome; CAD: coronary artery disease; NSTEMI: non ST‐ segment elevation myocardial infarction; STEMI: ST‐segment elevation myocardial infarction; UA: unstable angina. *For patients who didn’t receive fibrinolytic therapy or primary PCI

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eTable 10. Medications Used During Hospitalization for Patients Undergoing PCI

2001(n=407) 2006 (n=1393) 2011 (n=3660) P trend n Weighted % n Weighted % n Weighted % LMWH 266 64.7(60.0-69.3) 1140 80.8(78.7-82.9) 2833 74.6(73.2-76.0) .49 UFH 298 73.7(69.4-78.0) 761 50.6(48.0-53.2) 2071 60.8(59.2-62.4) .98 Bivalirudin NA NA NA Fondaparinux NA NA 186 5.2(4.5-5.9) <.001 GPIIb/IIIa NA 73 6.5(5.2-7.8) 965 26.1(24.7-27.5) <.001 Aspirin 364 91.2(88.5-94.0) 1326 94.0(92.7-95.2) 3590 97.6(97.1-98.1) <.001 Clopidogrel 51 11.1(8.0-14.1) 1336 96.4(95.4-97.4) 3604 98.7(98.3-99.1) <.001 Ticlopidine 324 81.2(77.4-85.0) 28 1.1(0.5-1.6) 2 0.1(0.0-0.2) <.001 Statin 234 60.1(55.4-64.9) 1212 85.3(83.5-87.2) 3505 94.6(93.9-95.4) <.001 GPIIb/IIIa= glycoprotein IIb/IIIa inhibitor; LMWH= low-molecucular heparin; UFH: unfractionated heparin

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eTable 11. Trends in Percutaneous Coronary Intervention Quality Metrics

2001(n=407) 2006 (n=1393) 2011 (n=3660) P Relative Weighted % Relative Weighted % Relative Weighted % trend frequency (95%CI) frequency (95%CI) frequency (95%CI) Proportion of primary PCI 5.0 6.5 3.0 procedures with recording of 1/45 14/181 18/409 .10 (0.0-11.4) (2.9-10.1) (1.4-4.7) hospital arrival time Proportion of primary PCI 1.1 0.0 0.5 procedures with recording of 1/45 0/181 3/409 .86 (0.0-4.1) (0.0-0.0) (0.0-1.3) balloon dilation time Proportion of documentation of PCI with missing 57.8 52.5 51.5 262/419 750/1476 1961/3961 .03 procedural success (53.1-62.6) (50.0-55.1) (50.0-53.1) indicators Proportion of successful procedures among PCIs 85.0 93.9 96.4 with complete 134/157 670/726 1898/2000 <.001 (79.4-90.6) (92.1-95.6) (95.6-97.3) documentation of success indicators Proportion of PCI procedures with serum 67.6 78.5 90.8 275/407 1083/1380 3261/3638 <.001 creatine assessed before (63.1-72.2) (76.3-80.6) (89.8-91.7) PCI* Proportion of PCI 23.4 27.0 31.8 procedures with serum 71/407 364/1380 1120/3638 <.001 (19.3-27.6) (24.7-29.3) (30.3-33.3) creatine assessed after PCI* Proportion of PCI procedures with cardiac 37.2 33.7 35.9 125/407 428/1380 1056/3638 .64 biomarkers assessed after (32.5-41.9) (31.2-36.1) (34.4-37.5) PCI* Proportion of PCI procedures with 69.2 72.3 76.8 261/419 1076/1476 2797/3961 <.001 documentation of contrast (64.8-73.6) (70-74.6) (75.5-78.1) volume Discharge Medications Proportion of patients with 35.3 34.3 36.3 missing discharge 376/1000 930/2755 2266/7486 .13 (32.3-38.3) (32.5-36) (35.3-37.4) medications Among patients with

discharge medications Proportion of patients with 50.5 71.6 73.8 291/624 1319/1825 3765/5220 <.001 documentation of statin (46.6-54.5) (69.6-73.7) (72.6-74.9) Proportion of patients with 71.1 79.8 82.5 413/624 1466/1825 4509/5220 <.001 documentation of aspirin (67.5-74.6) (78-81.7) (81.5-83.5) Proportion of patients with documentation of 87.5 96.5 97.5 180/212 906/955 2459/2507 <.001 Thienopyridine (clopidogrel (83.1-92) (95.4-97.7) (96.9-98.1) or ticlopidine )# PCI: percutaneous coronary intervention. * For the first PCI procedure if more than one procedure during a hospitalization, excluding transferred out. #among the patients with stent

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eTable 12. Unadjusted Rate of Adverse Outcomes of Patients Undergoing Primary PCI

2001(n=45) 2006 (n=179) 2011 (n=404) P trend n Weighted % n Weighted % n Weighted % Death 3 6.7 (0.0-14.0) 8 3.7 (0.9-6.5) 13 2.2 (0.8-3.6) .07 Death or 3 6.7 (0.0-14.0) 8 3.7 (0.9-6.5) 13 2.2 (0.8-3.6) .07 treatment withdrawal Composite 3 6.7 (0.0-14.0) 13 5.5 (2.2-8.8) 33 6.3 (3.9-8.7) .94 complications Any bleeding 3 5.6 (0.0-12.3) 19 14.3 (9.2-19.4) 53 17.0 .05 (13.3-20.7) Major bleeding 1 1.1 (0.0-4.1) 2 1.1 (0.0-2.6) 5 1.9 (0.6-3.2) .50 Blood transfusion 0 0.0 (0.0-0.0) 3 2.2 (0.1-4.3) 6 1.7 (0.4-3.0) .65 Composite complications: death or withdrawal, stroke or repeat target vessel revascularization. PCI: percutaneous coronary intervention.

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eFigure. Study Profile (Flow Chart)

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