International Stroke Conference
International Stroke Conference
March 01, 2012
3 min read

WARCEF: Warfarin, aspirin similar for prevention of stroke, death in HF

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International Stroke Conference 2012

NEW ORLEANS — Results of a large, head-to-head trial demonstrate that warfarin and aspirin have similar effects on the prevention of stroke and death in HF patients in sinus rhythm.

The 11-country, randomized, double blind, controlled Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial followed 2,305 patients (mean age, 61 years) for an average of 3.5 years. All participants had HF, were in sinus rhythm and had left ventricular ejection fraction of 35% or less (mean LVEF, 25%).

“Currently, no conclusive evidence identifies a preferred regimen for this population,” Shunichi Homma, MD, and colleagues wrote in the study abstract.

Shunichi Homma, MD
Shunichi Homma
Courtesy of the American Heart Association

The researchers randomly assigned patients to daily 325 mg aspirin (n=1,163) or warfarin (Coumadin, Bristol-Myers Squibb) in doses calibrated to a prespecified level of blood thinning (n=1,142; international normalized ratio, 2 to 3.5).

Death, ischemic stroke or intracerebral hemorrhage — the combined primary endpoint — was not significantly different between groups. It occurred at a rate of 7.47% per year among patients assigned to warfarin vs. 7.93% among patients assigned to aspirin (HR=0.93; 95% CI, 0.79-1.10).

However, “there was a suggestive benefit of warfarin for the primary outcome at 4 years and beyond,” Homma, Margaret Milliken Hatch professor of medicine at Columbia University, N.Y., said during a press conference.

When researchers examined components of the primary outcome, they found that warfarin reduced ischemic stroke risk throughout follow-up as compared with aspirin (0.72% per year vs. 1.36% per year; HR=0.52; 95% CI, 0.33-0.82).

Similarly, no difference was found for the main secondary outcome of death, ischemic stroke, intracerebral hemorrhage, MI or HF hospitalization between the warfarin (12.70% per year) and aspirin groups (12.15% per year; HR=1.07; 95% CI, 0.93-1.23).

Major hemorrhage occurred at a rate of 1.78% per year among patients assigned warfarin and 0.87% among patients assigned aspirin (rate ratio=2.05; P<001). The frequency of intracerebral and intracranial hemorrhage was similar between the two groups, according to Homma.

“As expected, the overall bleeding rate was higher with warfarin,” Homma stated in a press release. “However, not all bleeds are created equal, and the one that patients fear the most — bleeding within the brain — occurred rarely in both groups.”

Homma concluded, “Given no overall benefit of warfarin and increased risk for bleeding, in spite of suggestive benefit at 4 years and beyond, there is no compelling evidence to use warfarin or aspirin for all patients.”

The researchers said WARCEF is the largest-ever trial to compare anticoagulant and antiplatelet therapies in patients with low LVEF in sinus rhythm. Next, the group will study whether certain subgroups of patients benefit more from each treatment. – by Katie Kalvaitis

For more information:

Disclosure: Dr. Homma reports no relevant financial disclosures.


Larry B. Goldstein, MD, FAAN, FAHA
Larry B. Goldstein

There was no overall difference between warfarin and aspirin, but it seemed that as the patients were in the study for longer periods of time there seemed to be a diversion. There may be a time factor here that is important. We’re going to need to look at the data carefully once it is published to try to understand this a little better.

Larry B. Goldstein, MD, FAAN, FAHA
Cardiology Today Editorial Board member

Disclosure: Dr. Goldstein reports no relevant financial disclosures.


The WARCEF trial investigators should be acknowledged for conducting a large, randomized, comparative trial in this high-risk patient population. The routine use of antithrombotic therapy, whether platelet-directed or coagulation protein-directed, in patients with low ejection fraction in sinus rhythm is not currently considered standard of care. A careful review of the data from WARCEF may provide important hypothesis-generating perspective for the clinical research community.

Richard C. Becker, MD
Professor of Medicine
Duke University School of Medicine

Disclosure: Dr. Becker reports no relevant financial disclosures.

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