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Rivaroxaban (Xarelto) appeared on par with warfarin for prevention in atrial fibrillation (Afib) with a bioprosthetic mitral valve, the RIVER trial showed.

Mean time to death, major cardiovascular events (stroke, transient ischemic attack, valve thrombosis, systemic embolism not related to the central nervous system, and heart failure hospitalization), or major bleeding at 12 months came out at 347.5 days with the direct oral anticoagulant (DOAC) compared with 340.1 days on dose-adjusted warfarin, a difference that met criteria for noninferiority at P<0.001.

Among the components of that primary composite endpoint, rivaroxaban significantly reduced stroke incidence (0.6% vs 2.4%, HR 0.25, 95% CI 0.07 to 0.88), Otavio Berwanger, MD, PhD, of HCor Research Institute and Hospital Israelita Albert Einstein in São Paulo, Brazil, reported at the American Heart Association (AHA) virtual meeting.

Rivaroxaban also had numerically less major bleeding (7 vs 13 cases, 1.4% vs 2.6%, HR 0.54, 95% CI 0.21-1.35), death from cardiovascular causes or thromboembolic events (3.4% vs 5.1%, HR 0.65, 95% CI 0.35 to 1.20), and intracranial bleeds (none vs 5 cases, or 1.0%).

Valve thrombosis incidence was "very low" at five cases with rivaroxaban versus three with warfarin (P=0.48).

"Because of the low number of such events, these findings should be interpreted with caution," Berwanger's group noted in a paper released simultaneously online in the .

"Nevertheless, the direction of effects was generally consistent with those observed in landmark randomized trials and meta-analyses that tested rivaroxaban and other direct oral anticoagulants involving patients with atrial fibrillation."

Rivaroxaban was noninferior to warfarin in for prevention of stroke or systemic embolism, but that pivotal trial excluded patients with bioprosthetic valves.

Trials for the other DOACs have also included few, if any, Afib patients with bioprosthetic valves.

The pattern follows the historical path of warfarin, which was also first studied in nonvalvular Afib (nonrheumatic heart disease), noted Manesh Patel, MD, of Duke University in Durham, North Carolina, and vice chair of the AHA conference.

"The data has lagged because of the historic precedent of showing it was at least as good as warfarin before you could go study it in a new population," he told 番茄社区app at a press conference. "Now that they've been demonstrated to be effective and used broadly [in nonvalvular Afib], a lot of clinicians are wondering if they can use them in patients with bioprosthetic valves -- maybe not mechanical valves but bioprosthetic valves."

The DOACs have a narrower target in the thrombotic cascade, whereas warfarin is a fairly broad-based antithrombotic, added Donald Lloyd-Jones, MD, of Northwestern University in Chicago and chair of the conference program, as well as AHA president-elect.

"We've been a little bit nervous about using them in these patients who have foreign material in their heart," he told 番茄社区app. "When you add atrial fibrillation on top of that, we're particularly nervous. Because [with] the combination of an atrium that's not contracting and forcefully moving the blood through a mitral valve prosthesis and this foreign material, we think there's ."

With this positive "first look" in a large trial, he pointed out, "it may open the door to other patients with Afib and foreign material who require anticoagulation."

The trial included 1,005 adults with a bioprosthetic mitral valve and permanent, paroxysmal, or persistent Afib or flutter at 49 sites in Brazil who were randomized to 20-mg rivaroxaban once daily or dose-adjusted warfarin with a target international normalized ratio (INR) of 2.0 to 3.0.

Patients couldn't have had mitral-valve surgery within 48 hours, extremely high risk of bleeding, transient Afib caused by surgery, or a mechanical valve.

Overall, this was a lower risk population than in ROCKET AF, with a younger average age (59 vs 73), less history of stroke or transient ischemic attack (13% vs 55%), and lower mean CHA₂DS₂-VASc stroke risk score (2.6 vs 3.5), noted AHA session discussant Elaine Hylek, MD, MPH, of Boston University.

"Estimates of efficacy and safety will not necessarily translate to older patients for whom bioprosthetic valves would be preferred," she cautioned at the session.

Also, too few patients (95) were enrolled within 3 months of bioprosthetic valve surgery to conclude much about this high-risk period, she added.

"Since rivaroxaban does not require monitoring of the INR and has an anticoagulant effect that is more consistent and less influenced by food or concomitant medications than warfarin, it represents an attractive alternative for this patient population," the researchers concluded.

They cautioned that the trial was open-label and that the results could not be extrapolated to patients with a bioprosthetic aortic valve, mitral stenosis, or mechanical valves, although there are ongoing trials in those populations.

However, the blinded event adjudication was an advantage, and the median 65.5% of time in therapeutic range in the warfarin group was "excellent," Hylek noted.

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