A Study to Assess the Effectiveness and Safety of 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

Jul 03, 2019
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Presenter/Author:
Barry H. Greenberg, MD, FACC
Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Janssen Research and Development
Date Presented:
11/11/2018
Date Published:
06/25/2019
Date Updated:
07/03/2019
Original Posted Date:
08/27/2018
References

Contribution To Literature:

The COMMANDER HF trial failed to show that rivaroxaban was superior to placebo at preventing major adverse cardiovascular events.

Description:

The goal of the trial was to evaluate rivaroxaban compared with placebo among patients with chronic heart failure, sinus rhythm, and coronary disease.

Study Design

  • Randomized
  • Parallel
  • Blinded

Patients with chronic heart failure, sinus rhythm, and coronary disease were randomized to rivaroxaban 2.5 mg twice daily (n = 2,507) versus placebo (n = 2,515).

  • Total number of enrollees: 5,022
  • Duration of follow-up: median 21.1 months
  • Mean patient age: 67 years
  • Percentage female: 22%
  • Percentage with diabetes: 41%

Inclusion criteria:

  • Chronic heart failure ≥3 months in duration with an acute worsening in the last 21 days
  • Left ventricular ejection fraction ≤45%
  • Coronary artery disease
  • Sinus rhythm
  • Elevated natriuretic peptides (B-type natriuretic peptide [BNP] >200 or N-terminal pro-BNP >800)

Exclusion criteria:

  • High risk of bleeding
  • Atrial fibrillation or another condition that required anticoagulation
  • Myocardial infarction or coronary revascularization during the index event
  • Estimated glomerular filtration rate <20
  • Recent stroke or prior intracranial hemorrhage
  • Nonischemic cardiomyopathy

Principal Findings:

The primary efficacy outcome, all-cause mortality, myocardial infarction, or stroke, occurred in 25.0% of the rivaroxaban group compared with 26.2% of the placebo group (p = 0.27).

The primary safety outcome, fatal bleeding or bleeding into a critical space with potential to cause disability, occurred in 0.7% of the rivaroxaban group compared with 0.9% of the placebo group (p = 0.48).

Secondary outcomes:

  • All-cause mortality: 21.8% with rivaroxaban vs. 22.1% with placebo (p = not significant)
  • Fatal bleeding: 0.4% with rivaroxaban vs. 0.4% with placebo (p = not significant)
  • Sudden/unwitnessed death, myocardial infarction, ischemic stroke, pulmonary embolism/symptomatic deep vein thrombosis: 7.0 events per 100 patient-years in the rivaroxaban group vs. 8.5 events per 100 patient-years in the placebo group (p = 0.013)
  • All-cause stroke or transient ischemic attack (TIA): 1.3 events per 100 patient-years in the rivaroxaban group vs. 1.9 events per 100 patient-years in the placebo group (p = 0.02)

Interpretation:

Among patients with chronic heart failure, sinus rhythm, and coronary disease, rivaroxaban was not beneficial. Rivaroxaban did not reduce major adverse events compared with placebo. However, rivaroxaban versus placebo was associated with a reduction in stroke or TIA. Major bleeding was similar between treatment groups.

Rivaroxaban 2.5 mg twice daily versus placebo in addition to antiplatelet therapy was associated with a reduction in cardiovascular death, myocardial infarction, or stroke in the ATLAS ACS 2–TIMI 51 trial (post-myocardial infarction and unstable angina) and the COMPASS trial (stable coronary and/or peripheral arterial disease).

References:

Mehra MR, Vaduganathan M, Fu M, et al. A comprehensive analysis of the effects of rivaroxaban on stroke or transient ischaemic attack in patients with heart failure, coronary artery disease, and sinus rhythm: the COMMANDER HF trial. Eur Heart J 2019;Jun 25:[Epub ahead of print].

Presented by Dr. Barry H. Greenberg at the American Heart Association Annual Scientific Sessions (AHA 2018), Chicago, IL, November 11, 2018.

Zannad F, Anker SD, Byra WM, et al., on behalf of the COMMANDER HF Investigators. Rivaroxaban in Patients With Heart Failure, Sinus Rhythm, and Coronary Disease. N Engl J Med 2018;379:1332-42.

Editorial: Pfeffer MA, Tardif JC. COMMANDER HF — A Trial and an Answer. N Engl J Med 2018;379:1372-4.

Presented by Dr. Faiez Zannad at the European Society of Cardiology Congress, Munich, Germany, August 27, 2018.

Keywords: AHA Annual Scientific Sessions, AHA18, ESC Congress, ESC18, Anticoagulants, Arrhythmia, Sinus, Coronary Artery Disease, Heart Failure, Hemorrhage, Ischemic Attack, Transient, Metabolic Syndrome, Myocardial Infarction, Myocardial Ischemia, Natriuretic Peptide, Brain, Peptide Fragments, Primary Prevention, Stroke, Stroke Volume, Vascular Diseases


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