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.
OBJECTIVE
Thrombin 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.


METHODS
This 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.


CONCLUSIONS
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.
Inserm Centre d'Investigation Clinique CIC 1433, UMR 1116, CHU de Nancy, Institut Lorrain du Coeur et des Vaisseaux, Université de Lorraine, Nancy, France.
Faiez
F
Zannad
Department of Medicine, Cardiology Division, University of California, San Diego, La Jolla, CA, USA.
Barry
B
Greenberg
National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, England.
John G F
JG
Cleland
Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Mihai
M
Gheorghiade
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Dirk J
DJ
van Veldhuisen
Brigham and Women's Hospital Heart and Vascular Center, and Harvard Medical School, Boston, MA, USA.
Mandeep R
MR
Mehra
Division of Innovative Clinical Trials, Department of Cardiology, University Medical Centre Göttingen (UMG), Göttingen, Germany.
Stefan D
SD
Anker
Janssen Research & Development, LLC, 920 US 202, Raritan, NJ, USA.
William M
WM
Byra
Janssen Research & Development, LLC, 920 US 202, Raritan, NJ, USA.
Min
M
Fu
Janssen Research & Development, LLC, 920 US 202, Raritan, NJ, USA.
Roger M
RM
Mills
D000284:Administration, Oral; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D009203:Myocardial Infarction / Q000517:prevention & control*; D011446:Prospective Studies; D012107:Research Design; D012307:Risk Factors; D000069552:Rivaroxaban / Q000627:therapeutic use*; D020521:Stroke / Q000517:prevention & control*; D015996:Survival Rate
D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban
antithrombotic; coronary artery disease; heart failure; rivaroxaban; thrombin