Benefit of Warfarin Compared with Aspirin in Heart Failure Patients in Sinus Rhythm: A Subgroup Analysis of WARCEF, a Randomized Controlled Trial
Background—The Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial found no difference in the primary outcome between warfarin and aspirin in 2305 patients with reduced left ventricular ejection fraction in sinus rhythm. However, it is unknown if any subgroups benefit from warfarin or aspirin.
Methods and Results—We used a Cox model stepwise selection procedure to identify subgroups that may benefit from warfarin or aspirin on the WARCEF primary outcome. A secondary analysis added major hemorrhage to the outcome. The primary efficacy outcome was time to the first to occur of ischemic stroke, intracerebral hemorrhage, or death. Only age group was a significant treatment effect modifier (p for interaction 0.003). Younger patients benefitted from warfarin over aspirin on the primary outcome (4.81 vs. 6.76 events per 100 patient-years: HR 0.63, 95% CI 0.48-0.84, p=0.001). In older patients, therapies did not differ (9.91 vs. 9.01 events per 100 patient-years: HR 1.09, 95% CI 0.88-1.35, p=0.44). With major hemorrhage added, in younger patients the event rate remained lower for warfarin than aspirin (5.41 vs. 7.25 per 100 patient-years: HR 0.68, 95% CI 0.52-0.89, p=0.005), but in older patients it became significantly higher for warfarin (11.80 vs. 9.35 per 100 patient-years: HR 1.25, 95% CI 1.02-1.53, p=0.03).
Conclusions—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.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.
- Received February 13, 2013.
- Accepted July 10, 2013.