TY - JOUR
T1 - Rivaroxaban in Patients with Heart Failure, Sinus Rhythm, and Coronary Disease
AU - Zannad, Faiez
AU - Anker, Stefan D
AU - Byra, William M
AU - Cleland, John G F
AU - Fu, Min
AU - Gheorghiade, Mihai
AU - Lam, Carolyn S P
AU - Mehra, Mandeep R
AU - Neaton, James D
AU - Nessel, Christopher C
AU - Spiro, Theodore E
AU - van Veldhuisen, Dirk J
AU - Greenberg, Barry
AU - COMMANDER HF Investigators
AU - Weaver, W Douglas
AU - Dargie, Henry J.
AU - Klapholz, Marc
AU - Nyvad, Ole
AU - Nielsen, Tonny
AU - Schou, Morten
AU - Nielsen, Gitte
AU - Friedman, Keith
AU - Deering, Joseph
AU - Leonen, Marlo
PY - 2018
Y1 - 2018
N2 - 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 .).
AB - 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 .).
KW - Aged
KW - Coronary Artery Disease/complications
KW - Double-Blind Method
KW - Drug Therapy, Combination
KW - Factor Xa Inhibitors/adverse effects
KW - Female
KW - Follow-Up Studies
KW - Heart Failure/complications
KW - Humans
KW - Kaplan-Meier Estimate
KW - Male
KW - Middle Aged
KW - Myocardial Infarction/epidemiology
KW - Natriuretic Peptide, Brain/blood
KW - Patient Readmission/statistics & numerical data
KW - Platelet Aggregation Inhibitors/therapeutic use
KW - Rivaroxaban/adverse effects
KW - Stroke/epidemiology
KW - Stroke Volume
KW - Treatment Failure
U2 - 10.1056/NEJMoa1808848
DO - 10.1056/NEJMoa1808848
M3 - Journal article
C2 - 30146935
VL - 379
SP - 1332
EP - 1342
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 14
ER -