• Shunichi Homma, John L P Thompson, Min Qian, Siqin Ye, Marco R Di Tullio, Gregory Y H Lip, Douglas L Mann, Ralph L Sacco, Bruce Levin, Patrick M Pullicino, Ronald S Freudenberger, John R Teerlink, Susan Graham, J P Mohr, Arthur J Labovitz, Richard Buchsbaum, Conrado J Estol, Dirk J Lok, Piotr Ponikowski, Stefan D Anker, and WARCEF Investigators.
• From the Division of Cardiology, Department of Medicine (S.H., S.Y., M.R., D.T.) and Department of Neurology (J.P.M.), Columbia University Medical Center, New York, NY; Department of Biostatistics, Columbia University Mailman School of Public Health, New York, NY (J.L.P.T., M.Q., B.L., R.B.); University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Department of Medicine, Washington University, St. Louis, MO (D.L.M.); Department of Neurology, University of Miami Miller School of Medicine, FL (R.L.S.); Kent Institute of Medicine and Health Sciences, University of Kent, Canterbury, United Kingdom (P.M.P.); Division of Cardiology, Department of Medicine, Lehigh Valley Hospital, Allentown, PA (R.S.F.); Section of Cardiology, Department of Medicine, San Francisco VA Medical Center and School of Medicine, University of California San Francisco (J.R.T.); Division of Cardiology, Department of Medicine, SUNY Upstate Medical University, Buffalo, NY (S.G.); Department of Cardiovascular Medicine, University of South Florida, Tampa (A.J.L.); Centro Neurológico de Tratamiento y Rehabilitación, Buenos Aires, Argentina (C.J.E.); Department of Cardiology, Deventer Hospital, Deventer, The Netherlands (D.J.L.); Department of Heart Diseases, Wroclaw Medical University, Military Hospital, Wroclaw, Poland (P.P.); and Division of Innovative Clinical Trials, Department of Cardiology, University Medicine Göttingen, Göttingen, Germany (S.D.A.). sh23@columbia.edu.
• Circ Heart Fail. 2015 May 1; 8 (3): 504-9.

BackgroundThe aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin.Methods And ResultsWe used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0-5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P<0.001), death alone (adjusted P=0.001), and improved net clinical benefit (adjusted P<0.001). A similar trend was observed for the other 2 outcomes, but significance was not reached (adjusted P=0.082 for ischemic stroke and adjusted P=0.109 for major hemorrhage).ConclusionsIn patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.© 2015 American Heart Association, Inc.

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