ORIGINAL RESEARCH Management and 1-Year Outcomes of Patients With Newly Diagnosed Atrial Fibrillation and Chronic Kidney Disease: Results From the Prospective GARFIELD-AF Registry Shinya Goto, MD, PhD; Pantep Angchaisuksiri, MD; Jean-Pierre Bassand, MD; A. John Camm, MD; Helena Dominguez, MD, PhD; Laura Illingworth, MS; Harry Gibbs, MBBS; Samuel Z. Goldhaber, MD; Shinichi Goto, MD, PhD; Zhi-Cheng Jing, MD; Sylvia Haas, MD; Gloria Kayani, BSc; Yukihiro Koretsune, MD, PhD; Toon Wei Lim, MBBS, PhD; Seil Oh, MD, PhD; Jitendra P. S. Sawhney, MD, DM; Alexander G. G. Turpie, MD; Martin van Eickels, MD; Freek W. A. Verheugt, MD, PhD; Ajay K. Kakkar, MBBS, PhD; for the GARFIELD-F Investigators* Background-—Using data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD–Atrial Fibrillation), we evaluated the impact of chronic kidney disease (CKD) stage on clinical outcomes in patients with newly diagnosed atrial fibrillation (AF). Methods and Results-—GARFIELD-AF is a prospective registry of patients from 35 countries, including patients from Asia (China, India, Japan, Singapore, South Korea, and Thailand). Consecutive patients enrolled (2013–2016) were classified with no, mild, or moderate-to-severe CKD, based on the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative guidelines. Data on CKD status and outcomes were available for 33 024 of 34 854 patients (including 9491 patients from Asia); 10.9% (n=3613) had moderate-to-severe CKD, 16.9% (n=5595) mild CKD, and 72.1% (n=23 816) no CKD. The use of oral anticoagulants was influenced by stroke risk (ie, post hoc assessment of CHA2DS2-VASc score), but not by CKD stage. The quality of anticoagulant control with vitamin K antagonists did not differ with CKD stage. After adjusting for baseline characteristics and antithrombotic use, both mild and moderate- to-severe CKD were independent risk factors for all-cause mortality. Moderate-to-severe CKD was independently associated with a higher risk of stroke/systemic embolism, major bleeding, new-onset acute coronary syndrome, and new or worsening heart failure. The impact of moderate-to-severe CKD on mortality was significantly greater in patients from Asia than the rest of the world (P=0.001). Conclusions-—In GARFIELD-AF, moderate-to-severe CKD was independently associated with stroke/systemic embolism, major bleeding, and mortality. The effect of moderate-to-severe CKD on mortality was even greater in patients from Asia than the rest of the world. Downloaded from http://ahajournals.org by on March 5, 2019 Clinical Trial Registration-—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362. ( J Am Heart Assoc. 2019;8: e010510. DOI: 10.1161/JAHA.118.010510.) Key Words: atrial fibrillation • chronic kidney disease • GARFIELD-AF registry • outcomes research • registry pidemiologic studies suggested the increased preva- and CKD increases with age and concomitant risk factors.3–7 E lence of atrial fibrillation (AF) in patients with chronic Moreover, there are several common risk factors for high kidney diseases (CKDs).1,2 Indeed, the prevalence of both AF prevalence of AF and CKD such as hypertension, diabetes From the Tokai University School of Medicine, Kanagawa, Japan (Shinya G.); Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (P.A.); University of Besancßon, France (J.-P.B.); Thrombosis Research Institute, London, United Kingdom (J.-P.B., L.I., G.K., A.K.K.); St. George’s University of London, London, United Kingdom (A.J.C.); Bispebjerg-Frederiksberg Hospital, Copenhagen, Denmark (H.D.); Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (H.D.); The Alfred Hospital, Melbourne, Australia (H.G.); Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (S.Z.G.); Keio University School of Medicine, Tokyo, Japan (Shinichi G.); Fu Wai Hospital, State Key Lab of Cardiovascular Disease, National Center for Cardiovascular Disease, PUMC & CAMS, Beijing, China (Z.-C.J.); Formerly Klinikum rechts der Isar, Technical University of Munich, Germany (S.H.); National Hospital Organization, Osaka National Hospital, Osaka, Japan (Y.K.); National University Hospital, Singapore (T.W.L.); Seoul National University Hospital, Seoul, Korea (S.O.); Sir Ganga Ram Hospital, Delhi, India (J.P.S.S.); McMaster University, Hamilton, Canada (A.G.G.T.); Bayer AG, Berlin, Germany (M.v.E.); Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, The Netherlands (F.W.A.V.); University College London, London, United Kingdom (A.K.K.). Accompanying Tables S1 and S2 are available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.118.010510 *A complete list of the GARFIELD-AF Investigators can be found in the Appendix at the end of the article. Correspondence to: Shinya Goto, MD, PhD, Department of Medicine (Cardiology), Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259- 1193, Japan. E-mail: [email protected] Received September 21, 2018; accepted December 24, 2018. ª 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. DOI: 10.1161/JAHA.118.010510 Journal of the American Heart Association 1 Atrial Fibrillation and CKD—GARFIELD-AF Registry Goto et al ORIGINAL RESEARCH A better understanding of the impact of CKD on outcomes Clinical Perspective among patients with AF in the contemporary treatment setting is needed, assessing the impact of CKD and the What Is New? experience with anticoagulants beyond Western Europe and • The impact of increasing severity of chronic kidney disease North America. (CKD) on outcomes is well documented in studies con- The GARFIELD-AF (Global Anticoagulant Registry in the ducted in Western Europe and North America, but not the FIELD–Atrial Fibrillation) is an ongoing, international, prospec- rest of the world. tive registry of newly diagnosed patients with AF at risk of • The GARFIELD-AF (Global Anticoagulant Registry in the stroke. We aimed to clarify the relationship between CKD stage FIELD–Atrial Fibrillation) registry shows that 1 year after and clinical outcomes—reflecting real-world clinical practice diagnosis of atrial fibrillation, both mild and moderate-to- severe CKD were independent risk factors for all-cause during an era when non-VKA oral anticoagulants (NOACs) are mortality, after adjusting for baseline characteristics and available. Using global data from this noninterventional registry, antithrombotic use. we attempted to confirm the hypothesis that CKD stage • Moderate-to-severe CKD was also independently associated influences clinical outcomes among a highly diverse group of with a higher risk of stroke/systemic embolism, major newly diagnosed patients with AF. In addition, we aimed to bleeding, new-onset acute coronary syndrome, and new or clarify the impact of CKD on clinical outcomes in Asia, where worsening heart failure; the impact of moderate-to-severe both the clinical characteristics of patients as well as the CKD on mortality is even greater in patients from Asia, standard of care with antithrombotic therapy differ from the where patient characteristics and the standard of care for rest of the world (RoW).19 anticoagulation differs from the rest of the world. What Are the Clinical Implications? Methods fi • Despite potential concerns over the lack of coagulation The data that support the ndings of this study are available monitoring with non–vitamin K antagonist oral anticoagu- from the corresponding author upon reasonable request. lants in patients with moderate-to-severe CKD, the data from GARFIELD-AF suggest that the use of non–vitamin K Study Design and Participants antagonist oral anticoagulants in these patients is similar to The study design of GARFIELD-AF has been described Downloaded from http://ahajournals.org by on March 5, 2019 their use in no/mild CKD in real-world clinical practice. previously.20 Briefly, GARFIELD-AF is a contemporary, international, and sequentially recruited cohort of patients with newly diagnosed AF at risk of stroke. Men and women mellitus, and obesity.4–6 Thus, the number of patients with aged ≥18 years with nonvalvular AF diagnosed according to concomitant AF and CKD increases as the population ages. standard local procedures within the previous 6 weeks, and From a clinical outcomes perspective, comorbid CKD is with at least 1 risk factor for stroke as judged by the an independent predictor of stroke and bleeding events in investigator, are eligible for inclusion. Risk factors for patients with AF.8,9 Risk of stroke and hemorrhage in this stroke were not prespecified in the protocol, nor are they patient group increases progressively with declining renal limited to the components of existing risk stratification 10 function. Thus, the HAS-BLED (hypertension, abnormal schemes such as CHA2DS2-VASc score. Patients with a renal or liver function, stroke, bleeding, labile international transient reversible cause of AF and those for whom follow- normalized ratio, elderly, drugs predisposing to bleeding or up is not envisaged or possible were excluded. To minimize history of alcohol abuse) score, which was designed to recruitment bias, investigator sites have been selected predict the bleeding risk of patients with AF, includes “L” for randomly (apart from 18 sites, out of 1019) from all liver or kidney dysfunction.