In the largest and longest head-to-head comparison of two anti-clotting medications, warfarin and aspirin performed similarly well in preventing deaths and strokes in heart failure patients with normal heart rhythm, according to late-breaking research presented at the American Stroke Association’s International Stroke Conference 2012 in New Orleans.
“Although there was a warfarin benefit for patients treated for four or more years, overall, warfarin and aspirin were similar,” said Shunichi Homma, MD, lead author of the study and the Margaret Milliken Hatch Professor of Medicine at Columbia University in New York City.
In the 11-country Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial, researchers followed 2,305 patients with heart failure and normal heart rhythm for up to six years (average of 3.5 years). The patients were on average 61 years old, with left ventricular ejection fraction of less than 35% (normal is 55% or higher).
Of the patients in the study, 13% experienced a stroke or transient ischemic attack and were at heightened risk of recurrence. Patients with heart failure in general are at increased risk of death, blood clots and strokes.
Researchers randomly assigned patients to receive either 325 milligrams per day of aspirin or warfarin doses calibrated to a pre-specified level of anticoagulation. Warfarin therapy requires frequent blood testing to monitor its dosage to achieve the desired level of anticoagulation. To avoid bias, all patients had blood drawn on the same schedule and their pills adjusted so neither the patients nor their treating physicians knew which regimen they were taking.
Death, ischemic stroke or intracerebral hemorrhage, which combined were the study’s primary endpoint, occurred at a rate of 7.47% for patients assigned to warfarin and 7.93% for patients assigned to aspirin. The difference was not statistically significant.
However, “in the group of patients followed for more than three years, those on warfarin did better in comparison to the aspirin patients,” Homma said. Over the entire study period, patients receiving warfarin were slightly more than half as likely to develop a stroke as those taking aspirin. The rates of stroke were low, with annual rates of 0.72% in patients assigned to warfarin and 1.36% for those on aspirin.
Researchers evaluated the safety of the anti-clotting medications by monitoring major bleeding events other than intracerebral hemorrhage (since that was a primary endpoint). Each year, major bleeds occurred in 1.8% of patients on warfarin and 0.9% of those on aspirin — a statistically significant difference.
“As expected, the overall bleeding rate was higher with warfarin,” Homma said. “However, not all bleeds are equal, and the one that patients fear the most — bleeding within the brain — occurred rarely in both groups.” It occurred in 0.12% per year in the warfarin group and 0.05% per year in the aspirin group.
“Given that there is no overall difference between the two treatments and that possible benefit of warfarin does not start until after four years of treatment, there is no compelling reason to use warfarin, especially considering the bleeding risk”, Homma said.
The investigators are analyzing whether certain subgroups of patients benefited more from each treatment.