Xarelto works for prevention in Valvular Afib

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

Mean time to death, major cardiovascular events (stroke, transient ischemic attack, valvular thrombosis, systemic unrelated central nervous system embolism, and hospitalization for heart failure) or major bleeding at 12 months occurred at 347.5 days with direct oral anticoagulant (DOAC) versus 340.1 days with dose-adjusted warfarin, a difference that met the criteria for non-inferiority to P.<0.001.

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

Rivaroxaban also had numerically fewer 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 bleeding (none vs 5 cases, or 1.0%).

The incidence of valve thrombosis was “very low” in five cases with rivaroxaban compared to three with warfarin (P.= 0.48).

“Due to the low number of such events, these results should be interpreted with caution,” Berwanger’s group noted in a paper published simultaneously online in New England Journal of Medicine.

“However, the direction of the effects was generally consistent with those seen in randomized trials and meta-analyzes that tested rivaroxaban and other direct oral anticoagulants involving patients with atrial fibrillation.”

Rivaroxaban was non-inferior to warfarin in ROCKET AF for the prevention of stroke or systemic embolism, but this pivotal study excluded patients with bioprosthetic valves.

Evidence for other DOACs also included few, if any, Afib patients with bioprosthetic valves.

The model follows the historical path of warfarin, which was also first studied in non-valvular AFib (non-rheumatic heart disease), noted Manesh Patel, MD, of Duke University in Durham, North Carolina, and vice president of the conference. AHA.

“The data lagged behind due to the historical precedent of showing it was at least as good as warfarin before it could be studied in a new population,” he said. MedPage today at a press conference. “Now they have proven to be effective and widely used [in nonvalvular Afib], many doctors wonder if they can use them in patients with bioprosthetic valves – perhaps not mechanical valves but bioprosthetic valves. “

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

“We’ve been a little nervous about using them in these patients who have foreign material in their hearts,” he said. MedPage today. “When you add in atrial fibrillation, we’re particularly nervous. Why [with] the combination of an atrium that does not contract and forcefully moves blood through a mitral valve prosthesis and this foreign material, we think there is an extra risk. “

With this positive “first look” in a large study, he stressed, “it could open the door to other patients with Afib and foreign material who need anticoagulants.”

The study 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 an international normalized ratio ( INR) target of 2.0 to 3.0.

Patients could not have had mitral valve surgery within 48 hours, extremely high risk of bleeding, transient afib caused by surgery, or mechanical valve.

Overall, this was a lower risk population than ROCKET AF, with a younger mean 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.

“Efficacy and safety estimates will not necessarily translate into older patients for whom bioprosthetic valves would be preferred,” he cautioned during the session.

Furthermore, too few patients (95) were enrolled within 3 months of bioprosthetic valve surgery to draw much conclusions about this high-risk period, he added.

“Because rivaroxaban does not require monitoring of INR and has a more consistent and less influenced anticoagulant effect from food or concomitant medications than warfarin, it represents an attractive alternative for this patient population,” concluded the researchers.

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

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

Last updated November 14, 2020