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

Presented at ESC congress 2018: by Faiez Zannad (Vandoeuvre les Nancy, France)

Introduction and Methods

Most patients with heart failure and reduced ejection fraction (HFrEF) have coronary artery disease (CAD), and once they suffer a decompensation event, they have a poor prognosis with a high rate of re-hospitalization and death. Thrombin-mediated pathways influence the course of disease, and it had been hypothesized that their inhibition might be of benefit for such patients, but data with warfarin could not support this hypothesis.

In the randomized COMMANDER HF study, the efficacy and safety of the direct oral anticoagulant rivaroxaban was evaluated in HFrEF patients with significant CAD, and a recent decompentation. For this purpose, patients (n=5022) were randomized to receive either rivaroxaban 2.5 mg twice daily or placebo, on top of standard of care. Patients with atrial fibrillation were excluded.

The primary efficacy outcome was the composite of all-cause mortality, myocardial infarction, or stroke following an index event. The principal safety endpoint was the composite of fatal bleeding, or bleeding into a critical space (intracranial, intraspinal, intraocular, pericardial, intra-articular, retroperitoneal, intramuscular with compartment syndrome) with a potential for permanent disability.

Main results

• The primary efficacy endpoint occurred in 25.0% of rivaroxaban patients and in 26.2% of control group patients (HR: 0.94; 95%CI: 0.84-1.05; P=0.27).

The HRs for the individual elements of the primary efficacy endpoint were:

• All-cause mortality: 0.98 (95%CI: 0.87-1.10)
• MI: 0.83 (95%CI: 0.63-1.08)
• Stroke: 0.66 (95%CI: 0.47-0.95)

• None of the secondary and exploratory efficacy outcomes, including rehospitalization for HF, were significantly altered by treatment with rivaroxaban vs. placebo.
• The principal safety endpoint occurred in 0.7% of rivaroxaban patients and in 0.9% of controls (HR: 0.80; 95%CI: 0.43-1.49; P=0.484), whereas major bleeding events (according to the ISTH definition) occurred in 3.3% of rivaroxaban patients and in 2.0% of controls (HR: 1.68; 95%CI: 1.18-2.39; P=0.003).

Conclusion

In HFrEF patients with CAD and a recent decompensation, low-dose rivaroxaban on top of standard of care, did not significantly reduce all-cause mortality, MI, or stroke, compared with placebo, nor did it favorably affect the rate of HF rehospitalization.

Discussion

After the presentation in the press conference it was discussed whether a higher rivaroxaban dose may provide the expected clinical benefit, although it might also lead to higher major bleeding rates. It was questioned whether all patients were hospitalized, which was the case for 90% of the study population, whereas 10% were treated outside a ward with intravenous medications, which is considered to be equivalent to hospitalization. Moreover, it was explained that patients with atrial fibrillation were excluded from the study, or discontinued, because they needed open label anticoagulation.

Our reporting is based on the information provided at the ESC congress

This article was simultaneously published in NEJM