ACC23: Bayer and J&J's Xarelto reduces ischemia risk for PAD patients after revascularization surgery

Lower extremity revascularization (LER), a surgical procedure that can restore blood flow to blocked arteries in the legs, is often necessary for people with peripheral artery disease (PAD).

While it can save lives and limbs by preventing blood clots and other problems associated with poor circulation, it can also trigger one of the conditions that the procedure is designed to prevent—acute limb ischemia.

After LER, patients are four times more likely to experience ischemia, which is a sudden loss of blood flow that can be fatal or lead to permanent disability or amputation.

The standard of care for PAD patients who undergo LER is the age-old blood thinner aspirin. But according to prespecified analysis of the phase 3 VOYAGER PAD clinical trial, outcomes can be improved with the addition of Bayer and Johnson & Johnson’s Xarelto.

In the massive trial, which included 6,564 PAD patients in 34 countries, a twice-daily, 2.5-mg dose of Xarelto added to 100 mg per day of aspirin after LER reduced the chance of ischemia by 33% versus aspirin alone. The combination also produced a 15% reduction in major adverse limb and cardiovascular events. These effects remained constant over 30 days, 90 days and up to three years.  

The amplitude of the result and its sustainability over time was a surprise to the study’s chief investigator, Marc Bonaca, M.D. of the Division of Cardiovascular Medicine at the University of Colorado Anschutz Medical Campus.

“The reduction of these really bad limb complications early after the procedure was really large. I think that was impressive for what we usually see in cardiovascular disease,” Bonaca said in an interview.

The results of the study were presented Sunday at the American College of Cardiology’s (ACC's) 72nd Annual Scientific Session in New Orleans.

Two years ago at the ACC, another prespecified study from the same trial showed that Xarelto plus aspirin cut a variety of clot-related episodes including acute clots in limbs, amputation, heart attack, stroke and cardiovascular death by 14% over aspirin alone in patients who had undergone LER.  

Later in 2021, the FDA approved an expanded indication for Xarelto to include patients following a recent LER to relieve symptoms of PAD. Xarelto was approved for PAD in 2018 and remains the only anticoagulant endorsed for the condition.

Xarelto’s initial approval came in 2011 to reduce the risk of deep vein thrombosis in patients undergoing hip replacement surgery. In its second full year on the market it was a blockbuster. Worldwide sales peaked in 2021 at $7.5 billion before falling to $7.2 billion last year. Generic competition is expected to arrive in the U.S. in 2024.