← Back
NeuroTrials.ai
Neurology Clinical Trial Database

COMMANDER HF

Rivaroxaban in Patients with Heart Failure, Sinus Rhythm, and Coronary Disease

Share Share Copied! Compare

Year of Publication: 2018

Authors: Zannad F, Anker SD, Byra WM, ..., Greenberg B

Journal: The New England Journal of Medicine

Citation: Zannad F, et al. N Engl J Med. 2018;379(14):1332–1342.

Link: https://www.nejm.org/doi/full/10.1056/NEJMoa1808848

Clinical Question

Does low-dose rivaroxaban reduce the risk of death, myocardial infarction, or stroke in patients with worsening chronic heart failure, reduced ejection fraction, coronary artery disease, and in sinus rhythm?

Bottom Line

Rivaroxaban 2.5 mg BID did not reduce death/MI/stroke in patients with worsening chronic HFrEF (EF≤40%), CAD, sinus rhythm (HR 0.94; 95% CI 0.84-1.05; P=0.27). No individual component significant, though stroke was numerically lower (2.0% vs 3.0%; HR 0.66; 0.47-0.95). ISTH major bleeding increased (3.3% vs 2.0%; HR 1.68; P=0.003). 5,022 patients, 628 sites, 32 countries.

Major Points

  • Primary endpoint negative: death/MI/stroke 25.0% vs 26.2% (HR 0.94; 95% CI 0.84-1.05; P=0.27).
  • Stroke was the only component crossing 1.0: 2.0% vs 3.0% (HR 0.66; 0.47-0.95) — but no multiplicity adjustment.
  • HF rehospitalization identical: 37.2% vs 36.9% (HR 0.99) — thrombin-mediated events not primary driver of HF outcomes.
  • ISTH major bleeding increased: 3.3% vs 2.0% (HR 1.68; P=0.003).
  • Same 2.5 mg BID dose that benefited in COMPASS (stable CAD) and ATLAS ACS 2-TIMI 51 — but failed in HF setting.
  • 84.3% of deaths were cardiovascular — yet primary endpoint neutral, confirming HF deaths are not predominantly thrombin-mediated.
  • Near-universal guideline therapy: >92% ACEi/ARB, >92% beta-blockers, 76.5% MRAs.
  • BMI <25 subgroup showed nominally significant benefit (HR 0.76; P interaction=0.03) — needs caution.
  • Completes evidence base (with WASH, WATCH) against routine anticoagulation in HFrEF + sinus rhythm.
  • 5,022 patients, 628 sites, 32 countries. Industry-funded (Janssen). Median follow-up 21.1 months.

Design

Study Type: Randomized, double-blind, placebo-controlled

Randomization: 1

Blinding: Double-blind

Enrollment Period: 2013–2017

Follow-up Duration: Median 21.1 months

Centers: 628

Countries: 32 countries

Sample Size: 5022

Analysis: Intention-to-treat

Inclusion Criteria

  • Chronic heart failure ≥3 months
  • LVEF ≤40%
  • Coronary artery disease
  • Recent hospitalization (≤21 days) for worsening HF
  • Elevated BNP ≥200 pg/mL or NT-proBNP ≥800 pg/mL

Exclusion Criteria

  • Atrial fibrillation or need for long-term anticoagulation
  • Recent MI or PCI during index event
  • GFR <20 mL/min/1.73m²
  • Recent stroke or intracranial hemorrhage
  • Heart failure not due to coronary artery disease

Arms

FieldRivaroxaban 2.5 mg BIDControl
InterventionRivaroxaban 2.5 mg twice daily + standard carePlacebo + standard care
DurationMedian follow-up 21.1 monthsMedian follow-up 21.1 months

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Composite of death from any cause, MI, or strokePrimary26.2%25.0%0.940.27
All-cause mortalitySecondary22.1%21.8%0.98
Myocardial infarctionSecondary4.7%3.9%0.83
StrokeSecondary3.0%2.0%0.66
Major Bleeding (ISTH)Adverse2.0%3.3%1.680.003
Fatal or critical-space bleedingAdverse0.9%0.7%0.80.48

Subgroup Analysis

Subgroup analyses showed consistent results across strata; only stroke showed significant relative reduction (HR 0.66).

Criticisms

  • Primary endpoint not met; no overall benefit.
  • Higher major bleeding with rivaroxaban.
  • Events not centrally adjudicated.
  • Rate of trial discontinuation higher than expected.
  • Low use of CRT and ICD devices.

Funding

Janssen Research and Development

Based on: COMMANDER HF (The New England Journal of Medicine, 2018)

Authors: Zannad F, Anker SD, Byra WM, ..., Greenberg B

Citation: Zannad F, et al. N Engl J Med. 2018;379(14):1332–1342.

Content summarized and formatted by NeuroTrials.ai.