Rivaroxaban Noninferior to Warfarin in AFib Patients w/ Bioprosthetic Mitral Valves

Results of the RIVER trial suggest rivaroxaban (Xarelto) could be used instead of warfarin in patients with atrial fibrillation or flutter and a bioprosthetic mitral valve.

Presented at the American Heart Association (AHA) Scientific Sessions 2020, data from the trial indicated rivaroxaban 20 mg once daily was noninferior to warfarin for a primary endpoint of death, major cardiovascular events, and major bleeding—with a nonsignificant trend favoring rivaroxaban for most of the study’s secondary endpoints, including incidence of stroke.

“This is the largest trial designed to evaluate the safety and efficacy of direct oral anticoagulants in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. Earlier trials of direct oral anticoagulants vs. warfarin for atrial fibrillation or flutter together included fewer than 200 patients with bioprosthetic mitral valves,” said lead investigator Otavio Berwanger, MD, PhD, a cardiologist and the director of the Research Institute Hcor at Hospital de Coracao in Sao Paulo, Brazil, in a statement from the AHA.

With data suggesting off-label use of rivaroxaban and other direct oral anticoagulants in patients with bioprosthetic mitral valves who have atrial fibrillation or flutter, investigators designed the RIVER trial to further explore the potential safety and efficacy in this setting. Designed as a pragmatic, multicenter, open-label, randomized, noninferiority trial, RIVER was conducted across 49 sites and enrolled 1,005 patients.

Patients were considered eligible for inclusion in the trial at any time at least 48 hours after undergoing mitral valve surgery. Patients were excluded based on contraindications to either study drug, being at an extremely high risk of bleeding, transient atrial fibrillation caused by surgery, or if they received mechanical valves.

Patients included in the study were randomized in 1:1 ratio to receive either rivaroxaban or warfarin and followed for 12 months. Investigators pointed out patients with renal dysfunction were given 15 mg rivaroxaban and warfarin doses were titrated to maintain a target international normalized ratio (INR) between 2.0-3.0. The primary endpoint of the study was a composite of all-cause mortality, stroke, transit ischemic attack (TIA), major bleeding, valve thrombosis, systemic embolism not related to the central nervous system, or hospitalization for heart failure. Individual components of the primary endpoint, bleeding events, and venous thromboembolism as secondary endpoints for the trial.

In total, 505 patients were randomized to warfarin and 500 to rivaroxaban. The median age of study participants was 59.3 years, 60.4% were women, 60.7% had hypertension, 38.8% had heart failure, and 15.4% had a history of stroke or TIA. Additionally, investigates pointed out 95.6% of patients had atrial fibrillation and 4.3% had atrial flutter.

During the follow-up period, the mean time until a primary-outcome event occurred was 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (RMST difference: 7.4 days; 95% CI, -1.4 to 16.3; P <.001 for noninferiority and P=.10 for superiority). Deaths from cardiovascular causes or thromboembolic events occurred among 3.4% of patients in the rivaroxaban group and in 5.1% of patients in the warfarin group (HR, 0.65; 95% CI, 0.35-1.20). Further analysis suggested stroke occurred in 0.6% of the rivaroxaban group and 2.4% in the warfarin group (HR, 0.25; 95% CI, 0.07-0.88).

Safety analyses indicated major bleeding occurred among 1.4% of patients in the rivaroxaban group and 2.6% of patients in the warfarin group (HR, 0.54; 95% CI, 0.21-1.35) and revealed a similar frequency not other serious adverse events among the study groups.

“The results from the RIVER Trial are consistent with previous research, including ROCKET and other pivotal trials of DOACs, and can inform clinical practice for patients with bioprosthetic mitral valves,” Berwanger added. “For a subgroup of patients with a mitral valve replacement within the last three months, rivaroxaban was statistically and clinically superior to warfarin.”

This study, “Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve,” was presented at AHA 2020 and simultaneously published in the New England Journal of Medicine.