John R Teerlink1, Min Qian2, Natalie A Bello2, Ronald S Freudenberger3, Bruce Levin2, Marco R Di Tullio2, Susan Graham4, Douglas L Mann5, Ralph L Sacco6, J P Mohr2, Gregory Y H Lip7, Arthur J Labovitz8, Seitetz C Lee2, Piotr Ponikowski9, Dirk J Lok10, Stefan D Anker11, John L P Thompson2, Shunichi Homma12. 1. Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California San Francisco, San Francisco, California. 2. Columbia University Medical Center, New York, New York. 3. Lehigh Valley Hospital, Allentown, Pennsylvania. 4. State University of New York at Buffalo, Buffalo, New York. 5. Washington University, St. Louis, Missouri. 6. University of Miami, Miami, Florida. 7. Institute of Birmingham Centre for Cardiovascular Sciences, Birmingham, England, United Kingdom. 8. University of South Florida, Tampa, Florida. 9. Military Hospital, Wroclaw, Poland. 10. Deventer Hospital, Deventer, the Netherlands. 11. Innovative Clinical Trials, Department of Cardiology & Pneumology, University Medical Center Göttingen (UMG), Göttingen, Germany. 12. Columbia University Medical Center, New York, New York. Electronic address: sh23@cumc.columbia.edu.
Abstract
OBJECTIVES: The aim of this study was to determine whether aspirin increases heart failure (HF) hospitalization or death in patients with HF with reduced ejection fraction receiving anangiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). BACKGROUND: Because of its cyclooxygenase inhibiting properties, aspirin has been postulated to increase HF events in patients treated with ACE inhibitors or ARBs. However, no large randomized trial has addressed the clinical relevance of this issue. METHODS: We compared aspirin and warfarin for HF events (hospitalization, death, or both) in the 2,305 patients enrolled in theWARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial (98.6% on ACE inhibitor or ARB treatment), using conventional Cox models for time to first event (489 events). In addition, to examine multiple HF hospitalizations, we used 2 extended Cox models, a conditional model and a total time marginal model, in time to recurrent event analyses (1,078 events). RESULTS: After adjustment for baseline covariates, aspirin- and warfarin-treated patients did not differ in time to first HF event (adjusted hazard ratio: 0.87; 95% confidence interval: 0.72 to 1.04; p = 0.117) or first hospitalization alone (adjusted hazard ratio: 0.88; 95% confidence interval: 0.73 to 1.06; p = 0.168). The extended Cox models also found no significant differences in all HF events or in HF hospitalizations alone after adjustment for covariates. CONCLUSIONS: Among patients with HF with reduced ejection fraction in the WARCEF trial, there was no significant difference in risk of HF events between the aspirin and warfarin-treated patients. (Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction trial [WARCEF]; NCT00041938).
RCT Entities:
OBJECTIVES: The aim of this study was to determine whether aspirinincreases heart failure (HF) hospitalization or death in patients with HF with reduced ejection fraction receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). BACKGROUND: Because of its cyclooxygenase inhibiting properties, aspirin has been postulated to increase HF events in patients treated with ACE inhibitors or ARBs. However, no large randomized trial has addressed the clinical relevance of this issue. METHODS: We compared aspirin and warfarin for HF events (hospitalization, death, or both) in the 2,305 patients enrolled in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial (98.6% on ACE inhibitor or ARB treatment), using conventional Cox models for time to first event (489 events). In addition, to examine multiple HF hospitalizations, we used 2 extended Cox models, a conditional model and a total time marginal model, in time to recurrent event analyses (1,078 events). RESULTS: After adjustment for baseline covariates, aspirin- and warfarin-treated patients did not differ in time to first HF event (adjusted hazard ratio: 0.87; 95% confidence interval: 0.72 to 1.04; p = 0.117) or first hospitalization alone (adjusted hazard ratio: 0.88; 95% confidence interval: 0.73 to 1.06; p = 0.168). The extended Cox models also found no significant differences in all HF events or in HF hospitalizations alone after adjustment for covariates. CONCLUSIONS: Among patients with HF with reduced ejection fraction in the WARCEF trial, there was no significant difference in risk of HF events between the aspirin and warfarin-treated patients. (Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction trial [WARCEF]; NCT00041938).
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