Clinical Pearls & Morning Reports
Guimarães et al. conducted the Rivaroxaban for Valvular Heart Disease and Atrial Fibrillation (RIVER) trial — a randomized, noninferiority, open-label trial — to assess the efficacy and safety of rivaroxaban as compared with warfarin in patients with atrial fibrillation and a bioprosthetic mitral valve. Read the NEJM Original Article here.
Q: What was the rationale for performing the RIVER trial?
A: Rivaroxaban was shown to be noninferior to warfarin for the prevention of stroke or systemic embolism in ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), but patients with bioprosthetic valves were excluded from the trial.
Q: How was the treatment effect presented in the report of the RIVER trial?
A: In the RIVER trial, the treatment effect was presented as a between-group difference in the restricted mean survival time (RMST; rivaroxaban minus warfarin), so negative values indicate an increased risk from rivaroxaban treatment. The RMST method was selected because it is not dependent on the number of events and on the assumption of proportional hazards, as is the case in time-to-event analyses.
A: In this trial, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events (stroke, transient ischemic attack, valve thrombosis, systemic embolism not related to the central nervous system, or hospitalization for heart failure), or major bleeding at 12 months. The mean time until a primary-outcome event was 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (RMST difference, 7.4 days; 95% confidence interval [CI], −1.4 to 16.3; P<0.001 for noninferiority and P=0.10 for superiority). Secondary efficacy outcomes were generally similar in the two groups; the incidence of total stroke was 0.6% with rivaroxaban and 2.4% with warfarin. At 12 months, the composite secondary outcome of death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20).
A: With respect to bleeding events at 12 months, major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The incidence of clinically relevant nonmajor bleeding was similar in the rivaroxaban group and the warfarin group (4.8% and 4.6%, respectively). There were no reported intracranial bleeding events in the rivaroxaban group and 5 (1.0%) in the warfarin group. Similarly, the incidence of fatal bleeding was 0% in the rivaroxaban group and 0.4% in the warfarin group. The incidence of total bleeding events was not significantly different in the two groups.