Clinical Question

For patients with heart failure with reduced ejection fraction in sinus rhythm, is warfarin (Coumadin) therapy superior to aspirin regarding the risk of cardiac events and mortality?

Evidence-Based Answer

Heart failure increases the risk of thrombotic complications, but use of warfarin does not lower all-cause mortality more than aspirin in patients with heart failure with reduced ejection fraction in sinus rhythm. Warfarin lowered the rate of nonfatal cardiovascular events slightly (relative risk [RR] = 0.79; 95% confidence interval [CI], 0.63 to 1.00) but increased the risk of major bleeding complications (RR = 2.00; 95% CI, 1.44 to 2.78).¹ (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

Heart failure is a clinical syndrome associated with significant morbidity, mortality, and financial burdens. In chronic heart failure, cardiac structural abnormalities set off a cascade of maladaptive compensatory events that can lead to thrombotic complications, including thromboembolism and stroke.² For patients with heart failure in sinus rhythm, evidence-based pharmacologic treatment includes aspirin if atherosclerotic cardiovascular disease (ASCVD) is present.³ A previous Cochrane review by the same authors compared anticoagulation (i.e., warfarin) and placebo in patients with heart failure in sinus rhythm and found that it did not improve mortality or vascular events.⁴ For the current review, the authors performed a literature search to assess whether warfarin would be beneficial in this subset of patients with heart failure by comparing it with aspirin to decrease all-cause mortality, nonfatal cardiovascular events, and risk of major bleeding.

This Cochrane review included four randomized controlled trials (RCTs) and 3,663 patients.¹ All four studies had a low risk of selection bias and all compared warfarin with 162 mg, 300 mg, or 325 mg of aspirin in patients with clinically defined heart failure (i.e., with reduced left ventricular ejection fraction) in sinus rhythm. The analysis showed that there was no difference in all-cause mortality between warfarin and aspirin (RR = 1.00; 95% CI, 0.89 to 1.13), a consistent finding in all four RCTs. Although warfarin was associated with a non–statistically significant reduction in nonfatal cardiovascular events (e.g., myocardial infarction, stroke, pulmonary embolism; RR = 0.79; 95% CI, 0.63 to 1.00), it also led to a twofold higher risk of major bleeding (typically defined as a decline in hemoglobin level of more than 2 g per dL [20 g per L] or bleeding requiring transfusion; RR = 2.00; 95% CI, 1.44 to 2.78). There are no RCT data comparing non–vitamin K antagonist oral anticoagulants with antiplatelet agents in heart failure with reduced ejection fraction in sinus rhythm.

A trial comparing rivaroxaban (Xarelto) and placebo in patients with heart failure and ASCVD in sinus rhythm is ongoing.⁵ Current guidelines do not suggest a role for anticoagulants in patients with heart failure with reduced ejection fraction in sinus rhythm; aspirin should be used, especially in those with ASCVD.^3,6 Based on limited-quality evidence, this review confirms that warfarin has no benefit in patients with heart failure with reduced ejection fraction in sinus rhythm.

The practice recommendations in this activity are available at http://www.cochrane.org/CD003333.