NEJM: 10-year trial sheds no light on warfarin vs. aspirin for chronic HF

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Neither aspirin nor warfarin is superior for preventing a combined risk of death, stroke and cerebral hemorrhage in heart failure (HF) patients with normal heart rhythm, according to the 10-year WARCEF trial published May 2 in the New England Journal of Medicine.

The “role of oral anticoagulants as compared with aspirin has not been clarified in patients with chronic HF,” wrote principal investigator Shunichi Homma, MD, associate chief of the cardiology division at Columbia University Medical Center/NewYork-Presbyterian Hospital in New York City, and colleagues. “Early studies showed that anticoagulation reduced the rates of embolic events and death, but many patients in these trials had atrial fibrillation and clinical significant valvular heart disease, making interpretation of these results difficult.”

The WARCEF (Warfarin and Aspirin for Reduced Cardiac Ejection Fraction) trial is the largest double-blind comparison of these medications for heart failure, including 2,305 patients for up to six years at 168 study sites in 11 countries on three continents.

The researchers designed the trial to determine whether warfarin (with a target international normalized ratio of 2 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). The primary outcome was the time to the first event in a composite endpoint of ischemic stroke, intracerebral hemorrhage or death from any cause.  

In the head-to-head comparison, the combined risk of death, stroke, and cerebral hemorrhage was 7.47 percent per year for patients taking warfarin, and 7.93 percent per year for those taking aspirin—a difference that is not statistically significant. “In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant,” they wrote.

Patients taking warfarin had close to half the stroke risk of those taking aspirin (0.72 percent vs. 1.36 percent per year), the study authors reported. However, warfarin patients had more than twice the risk for major hemorrhage (1.78 percent vs. 0.87 percent per year). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin).

These results, the investigators reported, cancel each other out. However, in patients followed four years or longer, there was evidence that warfarin may be more effective in preventing the combined outcome of death, stroke and intracerebral hemorrhage.

“Since the overall risks and benefits are similar for aspirin and warfarin, the patient and his or her doctor are free to choose the treatment that best meets their particular medical needs. However, given the convenience and low cost of aspirin, many may go this route,” Homma said in a statement. The researchers added that follow-up analyses will further evaluate this evidence and seek to identify patients for whom one of the medications is preferred.

The research was supported by the National Institute for Neurological Disorders and Stroke, part of the National Institutes of Health.