Marco R Di Tullio1, Min Qian2, John L P Thompson2, Arthur J Labovitz2, Douglas L Mann2, Ralph L Sacco2, Patrick M Pullicino2, Ronald S Freudenberger2, John R Teerlink2, Susan Graham2, Gregory Y H Lip2, Bruce Levin2, J P Mohr2, Richard Buchsbaum2, Conrado J Estol2, Dirk J Lok2, Piotr Ponikowski2, Stefan D Anker2, Shunichi Homma2. 1. From the Division of Cardiology, Department of Medicine (M.R.D.T., S.H.), Department of Biostatistics, Mailman School of Public Health (M.Q., J.L.P.T., B.L., R.B.), and Department of Neurology (J.P.M.), Columbia University Medical Center, New York; Department of Cardiovascular Medicine, University of South Florida, Tampa (A.J.L.); Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO (D.L.M.); Departments of Neurology, Epidemiology and Public Health, University of Miami, FL (R.L.S.); Kent Institute of Medicine and Health Science, Canterbury, United Kingdom (P.M.P.); Division of Cardiology, Department of Medicine, Lehigh Valley Hospital, Allentown, PA (R.S.F.); Section of Cardiology, San Francisco Veterans Affairs Medical Center, University of California San Francisco (J.R.T.); Division of Cardiology, Department of Medicine, SUNY Upstate Medical University, Buffalo, NY (S.G.); University of Birmingham Centre for Cardiovascular Sciences, City Hospital, United Kingdom (G.Y.H.L.); Centro Neurológico de Tratamiento y Rehabilitación, Buenos Aires, Argentina (C.J.E.); Department of Cardiology, Deventer Hospital, The Netherlands (D.J.L.); Department of Heart Diseases, Wroclaw Medical University, Military Hospital, Poland (P.P.); and Department of Innovative Clinical Trials, University Medicine Göttingen (UMG), Germany (S.D.A.). md42@cumc.columbia.edu. 2. From the Division of Cardiology, Department of Medicine (M.R.D.T., S.H.), Department of Biostatistics, Mailman School of Public Health (M.Q., J.L.P.T., B.L., R.B.), and Department of Neurology (J.P.M.), Columbia University Medical Center, New York; Department of Cardiovascular Medicine, University of South Florida, Tampa (A.J.L.); Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO (D.L.M.); Departments of Neurology, Epidemiology and Public Health, University of Miami, FL (R.L.S.); Kent Institute of Medicine and Health Science, Canterbury, United Kingdom (P.M.P.); Division of Cardiology, Department of Medicine, Lehigh Valley Hospital, Allentown, PA (R.S.F.); Section of Cardiology, San Francisco Veterans Affairs Medical Center, University of California San Francisco (J.R.T.); Division of Cardiology, Department of Medicine, SUNY Upstate Medical University, Buffalo, NY (S.G.); University of Birmingham Centre for Cardiovascular Sciences, City Hospital, United Kingdom (G.Y.H.L.); Centro Neurológico de Tratamiento y Rehabilitación, Buenos Aires, Argentina (C.J.E.); Department of Cardiology, Deventer Hospital, The Netherlands (D.J.L.); Department of Heart Diseases, Wroclaw Medical University, Military Hospital, Poland (P.P.); and Department of Innovative Clinical Trials, University Medicine Göttingen (UMG), Germany (S.D.A.).
Abstract
BACKGROUND AND PURPOSE: In heart failure (HF), left ventricular ejection fraction (LVEF) is inversely associated with mortality and cardiovascular outcomes. Its relationship with stroke is controversial, as is the effect of antithrombotic treatment. We studied the relationship of LVEF with stroke and cardiovascular events in patients with HF and the effect of different antithrombotic treatments. METHODS: In the Warfarin Versus Aspirin in Reduced Ejection Fraction (WARCEF) trial, 2305 patients with systolic HF (LVEF≤35%) and sinus rhythm were randomized to warfarin or aspirin and followed for 3.5±1.8 years. Although no differences between treatments were observed on primary outcome (death, stroke, or intracerebral hemorrhage), warfarin decreased the stroke risk. The present report compares the incidence of stroke and cardiovascular events across different LVEF and treatment subgroups. RESULTS:Baseline LVEF was inversely and linearly associated with primary outcome, mortality and its components (sudden and cardiovascular death), and HF hospitalization, but not myocardial infarction. A relationship with stroke was only observed for LVEF of <15% (incidence rates: 2.04 versus 0.95/100 patient-years; P=0.009), which more than doubled the adjusted stroke risk (adjusted hazard ratio, 2.125; 95% CI, 1.182-3.818; P=0.012). In warfarin-treated patients, each 5% LVEF decrement significantly increased the stroke risk (adjusted hazard ratio, 1.346; 95% CI, 1.044-1.737; P=0.022; P value for interaction=0.04). CONCLUSIONS: In patients with systolic HF and sinus rhythm, LVEF is inversely associated with death and its components, whereas an association with stroke exists for very low LVEF values. An interaction with warfarin treatment on stroke risk may exist. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.
RCT Entities:
BACKGROUND AND PURPOSE: In heart failure (HF), left ventricular ejection fraction (LVEF) is inversely associated with mortality and cardiovascular outcomes. Its relationship with stroke is controversial, as is the effect of antithrombotic treatment. We studied the relationship of LVEF with stroke and cardiovascular events in patients with HF and the effect of different antithrombotic treatments. METHODS: In the Warfarin Versus Aspirin in Reduced Ejection Fraction (WARCEF) trial, 2305 patients with systolic HF (LVEF≤35%) and sinus rhythm were randomized to warfarin or aspirin and followed for 3.5±1.8 years. Although no differences between treatments were observed on primary outcome (death, stroke, or intracerebral hemorrhage), warfarin decreased the stroke risk. The present report compares the incidence of stroke and cardiovascular events across different LVEF and treatment subgroups. RESULTS: Baseline LVEF was inversely and linearly associated with primary outcome, mortality and its components (sudden and cardiovascular death), and HF hospitalization, but not myocardial infarction. A relationship with stroke was only observed for LVEF of <15% (incidence rates: 2.04 versus 0.95/100 patient-years; P=0.009), which more than doubled the adjusted stroke risk (adjusted hazard ratio, 2.125; 95% CI, 1.182-3.818; P=0.012). In warfarin-treated patients, each 5% LVEF decrement significantly increased the stroke risk (adjusted hazard ratio, 1.346; 95% CI, 1.044-1.737; P=0.022; P value for interaction=0.04). CONCLUSIONS: In patients with systolic HF and sinus rhythm, LVEF is inversely associated with death and its components, whereas an association with stroke exists for very low LVEF values. An interaction with warfarin treatment on stroke risk may exist. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.
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