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Chronic anticoagulation in patients with heart failure and reduced ejection fraction (HFrEF), but without atrial fibrillation (Afib, AF), has long been controversial; clinical trials have not demonstrated any benefit of warfarin use. This manufacturer-sponsored international trial assessed the efficacy of low doses of the direct-acting oral anticoagulant (DOAC) rivaroxaban — recently found to be efficacious combined with aspirin for chronic coronary artery disease (NEJM JW Cardiol Oct 2017 and N Engl J Med 2017; 377:1319) — in individuals with chronic HFrEF without AF, a recent HF exacerbation, and underlying coronary artery disease.
The study included 5,022 patients with 3 months or more HFrEF and a recent admission for decompensated HF (median age, 66 years; 23% women; median ejection fraction, 34%; prior myocardial infarction [MI], 76%). Participants were randomized to receive either rivaroxaban (2.5 mg twice daily) or placebo in addition to usual HF care (treatment with diuretics, β-blockers, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers exceeded 90% in both groups). After a median follow-up of 21 months, there was no difference between groups in the primary composite outcome of death from any cause, MI, or stroke (25% for rivaroxaban vs. 26% for placebo). There were also no differences in risk for fatal or potentially disabling bleeding (0.7% vs. 0.9%), but there was a significantly higher risk for major bleeding with rivaroxaban (3.3% vs. 2.0%).
Zannad F et al. Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease. N Engl J Med 2018 Aug 27; [e-pub]. (https://doi.org/10.1056/NEJMoa1808848)
Comment
Low-dose rivaroxaban did not improve outcomes in people with an acute exacerbation of chronic HFrEF with underlying coronary disease but without atrial fibrillation. These results contrast with those for rivaroxaban plus aspirin from COMPASS, which enrolled people with chronic atherosclerotic vascular disease, 21% of whom had a history of heart failure (although advanced heart failure was an exclusion criterion). Absent a clear indication such as AF or a prior thromboembolic event, there is no good evidence to support chronic anticoagulation — with either warfarin or DOACs — in patients with HFrEF.