BACKGROUND: The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain.
METHODS: In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months.
RESULTS: A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], -1.4 to 16.3; P<0.001 for noninferiority). 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). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). 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 frequency of other serious adverse events was similar in the two groups.
CONCLUSIONS: In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.).
This trial is thought-provoking for more than one reason. First, it addresses an important area of clinical uncertainty. Second, the statistical analytic approach used is relatively novel and makes one think about the advantages and disadvantages of this approach over traditional proportional hazards approaches.
This RCT specifically addresses a highly relevant clinical question regarding the efficacy and safety of DOACs for atrial fibrillation and bioprosthetic valve. The demonstration of significant non-inferiority of rivaroxaban (compared with warfarin) will likely impact on clinical practice, even though DOACs are already used in this patient population (based on prior limited RCT data).
More relevant for cardiologists and CT surgeons, but provides important new evidence about the role of NOACs over coumadin.
The comparison should take into account the TTR; that is, how well did INRs stay in the therapeutic range in the warfarin group?
Not a surprising result.
Seems to be a well done trial. The atrial fibrillation side of things is not new; however, there are few to no trials of DOACs in patients with any type of prosthetic valve.
Rivaroxaban in patients with AF who received tissue mitral valves (TMV) at around 55 yo with anticoagulation months to years later at 59 median age, so results may not apply to older TMV patients. Further, Table 1 reveals 2.6% more patients with older TMV received warfarin, biasing results as deterioration is near 30% by 5 years. Concerns about: As-treated analysis with complicated rivaroxoban patients intentionally switched to warfarin. Authors note open-label design could introduce bias, but assure that the funders had no role in anything, as often claimed with company-funded noninferiority studies. Critical warfarin patients had TTRs (INRs in the therapeutic range) a median of only 65.5% (interquartile range, 51.3 to 70.5%), not as bad as ROCKET-AF with very poor TTR of 55%. SPORTIF V taught you can’t show warfarin equivalence testing NOACs against moderately well managed warfarin patients, so RIVER gave expected outcome. Rivaroxoban is no worse in centers where INRs are not controlled.