A Randomized Study Comparing Rivaroxaban with Placebo in Subjects with Heart Failure and Significant Coronary Artery Disease Following an Episode of Decompensated Heart Failure: The COMMANDER HF study

Background There is mounting evidence of vascular and hemostatic dysfunction in patients with heart failure (HF) that may be associated with increased morbidity and mortality. Previous studies of vitamin K antagonists have demonstrated trends towards reduced rates of important clinical events in patients with HF, but these studies have been inconclusive. Rivaroxaban is a direct oral Factor Xa inhibitor that, at higher doses, is approved for conditions such as atrial fibrillation and venous thromboembolism. Administration of lower doses, in addition to antiplatelet and other background therapies, may modify vascular function, reduces the risk of thrombotic events and thereby improve clinical outcome in patients with HF, especially those with significant underlying coronary artery disease (CAD) and a recent episode of decompensated HF. Methods COMMANDER HF is a randomized, double-blind, placebo-controlled, event-driven trial which aims to establish the superiority of rivaroxaban compared with placebo in patients with significant CAD and reduced left ventricular ejection fraction (LVEF) following an episode of decompensated chronic HF. Patients were excluded if they had a history of persistent atrial fibrillation or were receiving anticoagulants for another reason. Patients were randomly assigned to receive rivaroxaban 2.5 mg twice daily, or matching placebo. All patients were to receive antiplatelet therapy, unless contraindicated, as well as standard HF therapy as prescribed by the treating physician. The primary efficacy endpoint is a composite of all-cause mortality, myocardial infarction (MI) and stroke. The primary safety outcome is the composite of fatal bleeding or bleeding into a critical organ or space with a potential for permanent disability. Results Preliminary data on the 5,022 subjects randomized at 628 sites in 32 countries indicate that the median age was 66 (IQR: 59; 74) years, 23% were women, the median eGFR was 66 (IQR: 52; 82) mL/minute, the median LVEF was 34 (IQR: 28; 38)% and 75% had a history of hypertension, 41% of diabetes and 75% of a prior MI. Follow-up ranged from 1 day to 50.4 months with a median of 17.5 months during which more than 1,200 primary efficacy endpoint events occurred. Conclusion The COMMANDER HF study will determine the efficacy and safety of low-dose rivaroxaban relative to placebo in the population enrolled. The results will be included in the final ESC presentation.