Xarelto works for the prevention of valve Afib

Rivaroxaban (Xarelto) appeared at the same level as 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, valve thrombosis, systemic embolism unrelated to the central nervous system, and hospitalization for heart failure) or major bleeding at 12 months occurred at 347.5 days with direct oral anticoagulant (DOA) versus 340.1 days on dose-adjusted warfarin, a difference that met criteria for non-inferiority to P<0.001.

Among the components of this composite primary 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, HCor Research Institute and Israelita Albert Einstein Hospital 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), deaths due to cardiovascular 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 versus three with warfarin (P= 0.48).

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

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

Rivaroxaban was not inferior to warfarin in ROCKET AF for the prevention of stroke or systemic embolism, but this pivotal trial excluded patients with bioprosthetic valves.

Trials for other DOAs also included few if any Afib patients with bioprosthetic valves.

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

“The data has lagged behind due to the historical precedent of showing that 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 that they have proven to be effective and widely used [in nonvalvular Afib], many clinicians 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, 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 the president-elect of the AHA.

“We were a little nervous about using them in these patients who have foreign bodies in their hearts,” he said. MedPage today. “When you add atrial fibrillation on top of that, we’re especially nervous. [with] the combination of a non-constricting atrium that forcefully moves blood through a prosthetic mitral valve and that foreign material, we believe there is an additional risk. “

With this positive “first look” in a large trial, he stressed, “this may open the door for other patients with Afib and foreign material who require anticoagulation.”

The trial included 1005 adults with a bioprosthetic mitral valve and permanent, paroxysmal, or persistent Afib or flutter at 49 sites in Brazil who were randomized to receive 20 mg of rivaroxaban once daily or warfarin at dose adjusted 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 in ROCKET AF, with a younger mean age (59 vs 73), less history of stroke or transient ischemic attack (13% vs 55%) and a lower average CHA₂DS₂-VASc stroke risk score (2.6 vs. 3.5), noted Elaine Hylek, MD, MPH, Boston University AHA session discussant.

“Efficacy and safety estimates will not necessarily translate into older patients for whom bioprosthetic valves would be preferred,” she warned at the meeting.

Additionally, 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 INR monitoring and has a more constant anticoagulant effect and less influenced by food or concomitant drugs than warfarin, it represents an interesting alternative for this patient population”, concluded the researchers.

They warned the trial was open and the results could not be extrapolated to patients with bioprosthetic aortic valve, mitral stenosis, or mechanical valves, although there are ongoing trials in these populations.

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

Last updated on November 14, 2020