Rivaroxaban in Patients with Heart Failure, Sinus Rhythm, and Coronary Disease
Open accessAbstract
BACKGROUND: Heart failure is associated with activation of thrombin-related pathways, which predicts a poor prognosis. We hypothesized that treatment with rivaroxaban, a factor Xa inhibitor, could reduce thrombin generation and improve outcomes for patients with worsening chronic heart failure and underlying coronary artery disease. METHODS: In this double-blind, randomized trial, 5022 patients who had chronic heart failure, a left ventricular ejection fraction of 40% or less, coronary artery disease, and elevated plasma concentrations of natriuretic peptides and who did not have atrial fibrillation were randomly assigned to receive rivaroxaban at a dose of 2.5 mg twice daily or placebo in addition to standard care after treatment for an episode of worsening heart failure. The primary efficacy outcome was the composite of death from any cause, myocardial infarction, or stroke. The principal safety outcome was fatal bleeding or bleeding into a critical space with a potential for causing permanent disability. RESULTS: Over a median follow-up period of 21.1 months, the primary end point occurred in 626 (25.0%) of 2507 patients assigned to rivaroxaban and in 658 (26.2%) of 2515 patients assigned to placebo (hazard ratio, 0.94; 95% confidence interval [CI], 0.84 to 1.05; P=0.27). No significant difference in all-cause mortality was noted between the rivaroxaban group and the placebo group (21.8% and 22.1%, respectively; hazard ratio, 0.98; 95% CI, 0.87 to 1.10). The principal safety outcome occurred in 18 patients who took rivaroxaban and in 23 who took placebo (hazard ratio, 0.80; 95% CI, 0.43 to 1.49; P=0.48). CONCLUSIONS: Rivaroxaban at a dose of 2.5 mg twice daily was not associated with a significantly lower rate of death, myocardial infarction, or stroke than placebo among patients with worsening chronic heart failure, reduced left ventricular ejection fraction, coronary artery disease, and no atrial fibrillation. (Funded by Janssen Research and Development; COMMANDER HF ClinicalTrials.gov number, NCT01877915 .).
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Trials of low-dose anticoagulation, PCSK9 inhibitors, and statins in patients with heart failure have been disappointing to date.
“Trials of low‐dose anticoagulation, 4 PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors, 5 as well as statins 2 , 6 in patients with HF have been disappointing to date”
From Impact of Icosapent Ethyl on Cardiovascular Risk Reduction in Patients With Heart Failure in REDUCE‐IT (2022) · cites this paper as [4]
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- Authors
- Zannad, F., Anker, S. D., Byra, W. M., Cleland, J. G. F., Fu, M., Gheorghiade, M., Lam, C. S. P., Mehra, M. R., Neaton, J. D., Nessel, C. C., Spiro, T. E., van Veldhuisen, D. J., & Greenberg, B.
- Affiliations
- Inserm (FR)
- Northwestern University (US)
- University Medical Center Groningen (NL)
- Brigham and Women's Hospital (US)
- University of Minnesota (US)
- Bayer (United States) (US)
- From the Université de Lorraine, INSERM Unité 1116 and Clinical Investigation Center 1433, French Clinical Research Infrastructure Network, Investigation Network Initiative–Cardiovascular and Renal Clinical Trialists, Centre Hospitalier Régional et Universitaire de Nancy, Vandoeuvre lès Nancy, France (F.Z.); the Department of Cardiology and Berlin–Brandenburg Center for Regenerative Therapies, German Center for Cardiovascular Research partner site Berlin, Charité Universitätsmedizin Berlin, Berlin ...
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-10-04
- Volume
- 379
- Issue
- 14
- Pages
- 1332-1342
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2888292644
- Cited by
- 345
- References
- 24
- Citations by year
- 2026: 14 · 2025: 29 · 2024: 29 · 2023: 31 · 2022: 46 · 2021: 52 · 2020: 66 · 2019: 67 · 2018: 11
- FWCI
- 37.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Janssen Research and Development
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- rivaroxaban, factor Xa inhibitors, chronic heart failure, coronary artery disease, thrombin generation, bleeding risk, myocardial infarction, stroke, all-cause mortality, natriuretic peptides, reduced left ventricular ejection fraction
- MeSH terms
- Rivaroxaban, Aged, Coronary Artery Disease, Double-Blind Method, Drug Therapy, Combination, Female, Follow-Up Studies, Heart Failure, Humans, Male, Middle Aged, Myocardial Infarction, Patient Readmission, Platelet Aggregation Inhibitors, Stroke Volume, Treatment Failure, Natriuretic Peptide, Brain, Stroke, Kaplan-Meier Estimate, Factor Xa Inhibitors
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