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Randomized Controlled Trial
. 2017 Aug;5(8):603-610.
doi: 10.1016/j.jchf.2017.04.011.

Aspirin Does Not Increase Heart Failure Events in Heart Failure Patients: From the WARCEF Trial

John R Teerlink  1 , Min Qian  2 , Natalie A Bello  2 , Ronald S Freudenberger  3 , Bruce Levin  2 , Marco R Di Tullio  2 , Susan Graham  4 , Douglas L Mann  5 , Ralph L Sacco  6 , J P Mohr  2 , Gregory Y H Lip  7 , Arthur J Labovitz  8 , Seitetz C Lee  2 , Piotr Ponikowski  9 , Dirk J Lok  10 , Stefan D Anker  11 , John L P Thompson  2 , Shunichi Homma  12 ; WARCEF Investigators
Affiliations
Randomized Controlled Trial

Aspirin Does Not Increase Heart Failure Events in Heart Failure Patients: From the WARCEF Trial

John R Teerlink et al. JACC Heart Fail. 2017 Aug.

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 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).

Keywords: aspirin; heart failure; hospitalization; survival; warfarin.

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Figures

Figure 1
Figure 1
Kaplan-Meier curves of death due to heart failure
Figure 2
Figure 2
Mean cumulative function curves for HF-related events (hospitalization or death)
Figure 3
Figure 3
Mean cumulative function curves of HF hospitalization.
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