Aspirin does not appear to increase heart failure events in patients with reduced ejection fraction

No difference was seen between aspirin-treated and warfarin-treated patients for time to any first heart failure event or to first heart failure hospitalization.

Aspirin did not appear to increase heart failure events when compared with warfarin in heart failure patients with reduced ejection fraction, according to a new study.

Researchers compared heart failure events, defined as hospitalization, death, or both, among patients in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial who were taking warfarin or aspirin. WARCEF was a multicenter trial that enrolled patients in 11 countries from October 2002 to January 2010. Most of the patients in the trial (98.6%) were also taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). The study analyzed time to first event and time to recurrent events using conventional and extended Cox models, respectively. Results were published in the August JACC: Heart Failure.

A total of 2,305 patients were included in WARCEF and were randomly assigned to receive warfarin, with a target international normalized ratio of 2.75 and an acceptable target range of 2.0 or 3.5, or to receive aspirin, 325 mg/d. All patients had left ventricular ejection fraction of 35% or lower in sinus rhythm. Mean follow-up was 3.5 years. Overall, there were 489 first heart failure events and 1,078 recurrent heart failure events. Once the researchers adjusted for baseline covariates, no difference was seen between aspirin-treated and warfarin-treated patients for time to any first heart failure event (adjusted hazard ratio, 0.87; 95% CI, 0.72 to 1.04; P=0.117) or to first heart failure hospitalization (adjusted hazard ratio, 0.88; 95% CI, 0.73 to 10.6; P=0.168). Likewise, time to any recurrent heart failure event or recurrent heart failure hospitalization did not differ by aspirin or warfarin treatment after covariate adjustment.

The authors noted that their findings might not be generalizable to all patients with heart failure and that their analysis did not include a placebo-controlled group, among other limitations. However, they concluded that in the WARCEF trial, no significant difference in risk for heart failure events was found in patients taking aspirin. “WARCEF provides important reassurance that the use of aspirin is not associated with an increase in clinically meaningful exacerbations of [heart failure] leading to hospitalization or an increase in death due to [heart failure], when compared to patients who were receiving warfarin,” the authors wrote.