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.
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Shunichi Homma
Courtesy
of the American Heart Association
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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.
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Larry B. Goldstein
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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.