Rationale and design of a randomized, double‐blind, event‐driven, multicentre study comparing the efficacy and safety of oral rivaroxaban with placebo for reducing the risk of death, myocardial infarction or stroke in subjects with heart failure and significant coronary artery disease following an exacerbation of heart failure: the COMMANDER HF trial

Abstract

AimsThrombin is a critical element of crosstalk between pathways contributing to worsening of established heart failure (HF). The aim of this study is to explore the efficacy and safety of rivaroxaban 2.5 mg bid compared with placebo (with standard care) after an exacerbation of HF in patients with reduced ejection fraction (HF‐rEF) and documented coronary artery disease.MethodsThis is an international prospective, multicentre, randomized, double‐blind, placebo‐controlled, event‐driven study of approximately 5000 patients for a targeted 984 events. Patients must have a recent symptomatic exacerbation of HF, increased plasma concentrations of natriuretic peptides (B‐type natriuretic peptide ≥200 pg/mL or N‐terminal pro–B‐type natriuretic peptide ≥800 pg/mL), with left ventricular ejection fraction ≤40% and coronary artery disease. Patients requiring anticoagulation for atrial fibrillation or other conditions will be excluded. After an index event (overnight hospitalization, emergency department or observation unit admission, or unscheduled outpatient parenteral treatment for worsening HF), patients will be randomized 1:1 to rivaroxaban or placebo (with standard of care). The primary efficacy outcome event is a composite of all‐cause mortality, myocardial infarction or stroke. The principal safety outcome events are the composite of fatal bleeding or bleeding into a critical space with potential permanent disability, bleeding events requiring hospitalization and major bleeding events according to International Society on Thrombosis and Haemostasis bleeding criteria.Conclusion COMMANDER HF is the first prospective study of a target‐specific oral antithrombotic agent in HF. It will provide important information regarding rivaroxaban use following an HF event in an HF‐rEF patient population with coronary artery disease.

Sex‐Specific Associations of Oral Anticoagulant Use and Cardiovascular Outcomes in Patients With Atrial Fibrillation

“…By inhibiting steps preceding thrombin generation, RIVA is suspected to inactivate the abovementioned thrombin cascade . With this underlying hypothesis, the Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure (COMMANDER‐HF) trial is assessing the efficacy of RIVA in reducing HF readmissions as a secondary end point among patients with HF and coronary artery disease. DABI, a direct thrombin inhibitor, may also have similar benefits, but human experiments are not yet evaluating this hypothesis.…”

Aspirin in heart failure: don't throw the baby (aspirin) out with the bathwater

“…As a result, there is a rationale for using antithrombotic agents to treat patients with ‘ischaemic’ heart failure who are in sinus rhythm. While the role of VKAs is now truly minor, the possible role of one of the non‐vitamin K antagonist oral anticoagulants is the subject of a current trial (COMMANDER) . The use of aspirin is here much more widespread, and yet is the subject of controversy.…”

September 2017 at a glance: epidemiology, prognosis, Mediterranean diet and different viewpoints on aspirin

“…This is aimed at gathering editorials, which may have been invited or not, showing different views regarding a similar topic. We start with a major controversial issue, maybe going to find a new perspective with recent trials with direct oral anticoagulants, the use of aspirin in patients with heart failure (HF). The trigger was an article by Chin et al ., showing that aspirin had no impact on the beneficial effects of eplerenone in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure (EMPHASIS‐HF) trial .…”