A subgroup analysis of a clinical trial found that younger patients taking warfarin were less likely to experience a composite endpoint of ischemic stroke, intracerebral hemorrhage or death. They were also less likely to experience stroke and death separately, with or without hemorrhage.
Researchers led by Shunichi Homma, MD, of Columbia University Medical Center in New York City, utilized data from the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) study. Their results were published online July 23 in Circulation: Heart Failure.
The WARCEF clinical trial took place between October 2002 and January 2010 and enrolled patients with left ventricular ejection fraction less than or equal to 35 percent in sinus rhythm from 168 centers in 11 countries. There were a total of 2,305 patients included in the study.
The participants were randomly assigned to receive warfarin (Coumadin, Bristol-Myers Squibb), with a target international normalized ratio of 2.75 and an acceptable target range of 2 to 3.5, or 325 mg of daily aspirin.
WARCEF researchers assessed the effect of both drugs on the primary outcome of time to the first occurrence of ischemic stroke, intracerebral hemorrhage or death and found no difference between the two medications.
Homma and his co-authors took the analysis another few steps and examined the effects of warfarin and aspirin on the primary outcome based on a number of different variables, including age, gender, body mass index and certain pre-existing conditions.
“The primary aim of WARCEF was to compare warfarin and aspirin in the general HF [heart failure] population, and not among different subgroups,” the authors explained.
There were a total of 622 events, with 302 in warfarin participants and 320 in aspirin patients. Age and country were the only two variables that led to significantly different outcomes between the two groups.
“In patients under 60 years, warfarin improved outcomes over aspirin with or without inclusion of major hemorrhage. In patients 60 years and older, there was no treatment difference, but the aspirin group had significantly better outcomes when major hemorrhage was included,” the authors wrote.
In the group of younger warfarin patients, there were 4.81 events per 100 patient-years compared with 6.76 events per 100 patient-years for the aspirin group.
Warfarin also significantly benefited patients in Poland. There were 7 events per 100 patient-years compared with 12.38 events per 100 patient-years in the aspirin group.
When hemorrhaging was taken into account, younger patients still derived benefit from warfarin, but older patients did not—there were more adverse outcomes among patients older than 60.
The authors noted some limitations of their study. There was no placebo group and the mechanism behind the results was not clear. There also may have been other variables that affected the results and there was no correction for the number of variables.
Despite the limitations, the authors stressed the importance of their findings, given the millions of people living with heart failure.
“A pivotal trial to confirm the possible benefit of warfarin for younger patients is warranted given the potentially large impact on treatment of HF patients,” they concluded.