Warfarin Ineffective for HF Without Atrial Fibrillation

In the WARCEF trial, reduced stroke rates were offset by increased bleeding.
The benefits of chronic anticoagulation in patients with heart failure (HF) who do not have atrial fibrillation are controversial. Previous clinical trials were underpowered to generate conclusive evidence, and results of observational studies have conflicted.
In the international WARCEF trial, investigators compared warfarin with aspirin in 2305 patients without a contraindication to anticoagulation (mean age, 61; 80% men). All were in sinus rhythm and had systolic left ventricular ejection fractions less than 35% (mean, 25%). Patients were randomized to receive warfarin (target international normalized ratio [INR], 2.0–3.5; mean, 2.5) or aspirin (325 mg) daily. Sites received sham INR results for patients in the aspirin group.
At a mean follow-up of 3.5 years, the rate of the primary endpoint of ischemic stroke, intracerebral hemorrhage, or all-cause death did not differ significantly between the warfarin and aspirin groups (7.47 and 7.93 per 100 patient-years, respectively). Rates of ischemic stroke were significantly lower with warfarin than with aspirin (0.72 vs. 1.36 per 100 patient-years), but rates of major hemorrhage were twice as high (1.78 vs. 0.87 per 100 patient-years). During follow-up, patients in the warfarin group were within the target INR range 63% of the time.
Comment: WARCEF showed no net benefit of warfarin in patients in sinus rhythm with systolic heart failure. Up to now, in the absence of evidence, the use of anticoagulation in this patient population has presumably depended on the instincts of the treating clinician. This well-designed clinical trial injects much-needed evidence into the decision; however, whether clinicians will change their practices based on the results remains to be seen. Furthermore, we don't know whether newer agents, which may provide more reliable anticoagulation than warfarin, might be beneficial in this context.
— Frederick A. Masoudi, MD, MSPH, FACC, FAHA
Published in Journal Watch Cardiology May 9, 2012