No mortality benefit to warfarin over aspirin for HF patients in sinus rhythm (WARCEF)

General

Clinical Question:
As compared with aspirin, does the use of warfarin improve outcomes in patients with severe systolic dysfunction who are in sinus rhythm?

Bottom Line:
Although it is clear that warfarin prevents strokes, it also increases major bleeding and does not affect mortality when compared with aspirin in patients with heart failure with reduced systolic function who are in sinus rhythm. Given the low baseline rate of strokes in this population and the higher risk of bleeding with warfarin, aspirin may be a better choice for these patients. (LOE = 1b)

Reference:
Homma S, Thompson JL, Pullicino PM, et al, for the WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med 2012;366(20):1859-1869.  [PMID:22551105]

Study Design:
Randomized controlled trial (double-blinded)

Funding:
Government

Allocation:
Concealed

Setting:
Outpatient (any)

Synopsis:
These investigators enrolled adult patients with normal sinus rhythm and heart failure with left ventricular ejection fraction (LVEF) of 35% or less. They excluded patients at high risk of cardiac embolism, such as those with mechanical valves or endocarditis. Using concealed allocation, 2305 patients were randomized to receive either warfarin or aspirin along with the corresponding placebo. All patients had blood draws that were processed at centralized laboratories to achieve a target international normalized ratio (INR) of 2.0 to 3.5. To maintain masking, the study analysis center provided fabricated but plausible INR results for patients in the aspirin group as if they were receiving active warfarin. There were no differences in baseline characteristics of the 2 groups: 80% of patients were male, the mean age was 61 years, the mean LVEF was 25%, and more than 80% of the patients were New York Heart Association Class I or II. Analysis was by intention to treat and the average follow-up period was 3.5 years. For the combined primary outcome of time to death or first ischemic or hemorrhagic stroke, there was no significant difference between the 2 groups overall. Although the warfarin group did have fewer patients with ischemic stroke (2.5% vs 4.7%; hazard ratio [HR] = 0.52; 95% CI, 0.33-0.82; number needed to treat = 45), it also had a higher number of patients with major hemorrhage (5.8% vs 2.7%; odds ratio = 2.21; 1.42-3.47; number needed to treat to harm = 32). Of note, for patients who were followed up for 4 years or longer, there was a small benefit in the primary outcome in the warfarin group (HR = 0.76; P = .04).

No mortality benefit to warfarin over aspirin for HF patients in sinus rhythm (WARCEF)is the Evidence Central Word of the day!