Rivaroxaban is noninferior to warfarin regarding the mean time until death, major cardiovascular events, or major bleeding at 12 months among patients with atrial fibrillation (AF) and a bioprosthetic mitral valve, according to study results in the New England Journal of Medicine.

In the randomized Rivaroxaban for Valvular Heart Disease and Atrial Fibrillation (RIVER) trial, researchers compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2-3). The primary outcome was a composite of death, major adverse cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months.

Investigators enrolled a total of 1005 patients at 49 sites in Brazil. The mean age of participants was 59.3 plus or minus 12.1 years, and 60.4% were women. In addition, 60.7% of the cohort had hypertension, 38.8% had congestive heart failure, 15.3% had a history of stroke or transient ischemic attack, 95.5% had AF, and 4.3% had atrial flutter.

The investigators found that a primary outcome event occurred at a mean of 347.5 days in patients in the rivaroxaban group compared with 340.1 days among patients in the warfarin group (95% CI, −1.4 to 16.3, Pnoninferiority = .001). Death from cardiovascular causes or thromboembolic events occurred in 17 (3.4%) patients in the rivaroxaban group compared with 26 (5.1%) participants in the warfarin group (hazard ratio [HR] 0.65; 95% CI, 0.35-1.2).


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Stroke incidence was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (HR 0.25; 95% CI, 0.07-0.88). Also, 7 (1.4%) patients in the rivaroxaban group had major bleeding compared with 13 (2.6%) in the warfarin group (HR 0.54; 95% CI, 0.21-1.35). Other serious adverse events were similar in the 2 treatment groups.

“In the RIVER trial involving patients with [AF] who had undergone bioprosthetic mitral-valve surgery, those who received rivaroxaban for 1 year were free of a composite primary outcome of death, major cardiovascular events, or major bleeding for a mean of 7.4 days longer than their counterparts who received warfarin,” stated the study authors. “In addition, the [CI] for the primary analysis may have excluded an effect size of more than 1.4 days free from events favoring warfarin, which showed the noninferiority effect of rivaroxaban in this clinical setting.”

The investigators noted several study limitations. The open-label design could have introduced bias in determining or reporting of events. Also, the findings cannot be extrapolated to patients with a bioprosthetic aortic valve or to persons with mitral stenosis or with mechanical valves.

“Finally, the as-treated and per-protocol analyses used restricted populations based on post-randomization variables such as adherence to the trial drugs, which could have influenced these results,” the researchers stated.

Disclosures: The study was supported by the Brazilian Ministry of Health (PROADI-SUS) and Bayer HealthCare Pharmaceuticals. Some of the authors reported affiliations with pharmaceutical and medical device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Guimarães HP, Lopes RD, de Barros e Silva PGM, et al. Rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve. N Engl J Med. 2020;383(22):2117-2126. doi: 10.1056/NEJMoa2029603