Rivaroxaban is non-inferior to warfarin in terms of efficacy and safety in the management of patients with atrial fibrillation and a bioprosthetic mitral valve.
The Rivaroxaban for Valvular Heart Disease and Atrial Fibrillation (RIVER) trial, published in the NEJM, randomised 1,005 patients to either rivaroxaban (20 mg once daily) or warfarin (adjusted to INR 2.0-3.0).
The study found the cumulative incidence of the primary outcome, a composite of death, major cardiovascular events, or major bleeding at 12 months, was similar in both patient groups.
“The mean time until a primary-outcome event was 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (p <0.001 for noninferiority).
In secondary outcomes, the composite outcome of death from cardiovascular causes or thromboembolic events at 12 months occurred in 3.4% of the rivaroxaban group and 5.1% of the warfarin group (HR 0.65).
The incidence of total stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (HR 0.25).
Valve thrombosis occurred in 1.0% of patients in the rivaroxaban group and in 0.6% of patients in the warfarin group. Other secondary efficacy outcomes were not significantly different in the two groups.
The incidence of total bleeding events was not significantly different in the two groups. Major bleeding occurred in 1.4% of the rivaroxaban group compared to 2.6% of the warfarin group (HR 0.54).
“The incidence of clinically relevant nonmajor bleeding was similar in the rivaroxaban group and the warfarin group (4.8% and 4.6%, respectively),” the study said.
Professor David Brieger, lead author of Australia’s AF guidelines, told the limbic that the findings confirm standard practice here.
“It just confirms our practice of prioritising the DOACs over warfarin in patients with nonvalvular AF. This justifies that practice in a subset of patients in whom we didn’t have very much data until now.”
“Prior to this study we had a total of 60 patients involved in the dabigatran trial or the apixaban trial. And that was our evidence base.”
“Yet we still made a recommendation that it was reasonable to use the DOACs in these patients on the basis of 60 patients. And the reason for that was because there wasn’t compelling evidence that the bioprosthetic valves themselves increase thrombotic risk necessarily.”
He said uncertainty around the definitions of valvular versus non-valvular AF had effectively muddied the waters.
“As time has gone on, we’ve adopted a more restrictive definition of what constitutes valvular AF so that our guidelines now limit valvular AF to patients who have AF in the context of mechanical prosthetic valves or AF in the context of moderate to severe mitral stenosis.”
Professor Brieger said the early termination of the RE-ALIGN study due to an excess of events in patients with mechanical prosthetic valves taking dabigatran hadn’t helped.
“So that sounded a note of alarm that we certainly shouldn’t be using DOACs in patients with mechanical prosthetic valves. And by extension, I suspect that the company was concerned that caution may have spilled over into bioprosthetic valves and steered clinicians away from using it in that population also.”
“But this now reassures us that we can safely do that. It’s reassuring because if you look at the event rates, they are all trending in favour of rivaroxaban rather than the reverse, which hasn’t always been the case with these therapies.”