VOYAGER PAD Analysis Evaluates Benefit of Janssen’s Xarelto Plus Aspirin After Lower Extremity Revascularization

March 5, 2023—The Janssen Pharmaceutical Companies of Johnson & Johnson announced data from a new prespecified analysis from the phase 3 VOYAGER PAD clinical trial.

The analysis showed that the company’s Xarelto (rivaroxaban) vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily) resulted in a 33% reduction in acute limb ischemia and a 15% reduction in major adverse limb and cardiovascular events, with or without dual antiplatelet therapy (DAPT), after lower extremity revascularization (LER) in patients with peripheral artery disease (PAD). The findings reinforced the benefits of Xarelto versus standard of care (aspirin alone) with consistent benefit shown at 30 days, 90 days, and up to 3 years after LER, stated the company.

The company noted that after LER, patients with PAD are four times more likely to experience acute limb ischemia, which is often associated with long hospitalizations and high incidences of amputation, disability, and death unless appropriate treatment is given.

The data were presented at ACC.23/WCC, the American College of Cardiology’s annual scientific session together with the World Congress of Cardiology held March 4-6, 2023, in New Orleans, Louisiana.

Marc P. Bonaca, MD, from the Department of Medicine, Division of Cardiovascular Medicine, at University of Colorado Anschutz Medical Campus in Aurora, Colorado, is the lead study author of the analysis.

“These data demonstrate an evolution in the medical therapy of patients undergoing LER for symptomatic PAD, where the addition of low-dose rivaroxaban to antiplatelet therapy results in a 33% reduction in major adverse limb events both early and late and with a consistently favorable benefit risk,” commented Dr. Bonaca in the Janssen press release. “We hope these data assist clinicians in understanding how to implement antithrombotic therapy in practice and overall support initiation of rivaroxaban in the first days after revascularization regardless of whether or not DAPT is utilized.”

As summarized in Janssen’s press release, the study found that patients treated with Xarelto plus aspirin after LER experienced a 33% reduction in acute limb ischemia, with a trend toward greater benefit observed early (≤ 30 days; hazard ratio [HR], 0.45; 95% CI, 0.24-0.85) versus late (> 90 days; HR, 0.75; 95% CI, 0.60-0.95).

Xarelto plus aspirin was more effective than antiplatelet therapy alone in preventing acute limb ischemia after LER (Kaplan-Meier estimate from 0 to 90 days, 1.02% vs 2.1% and from 91 days to 3 years, 4.3% vs 5.7%). The HR for the rate of thrombolysis in myocardial infarction (TIMI) major bleeding from day 0 to day 90 was 2.01 (range, 0.9-4.47); from day 91 up to 3 years, it was 1.28 (range, 0.82-1.99). Neither were statistically significant.

Janssen stated that the phase 3 VOYAGER PAD study was composed of 6,564 patients from 542 sites across 34 countries worldwide. Patients were randomized in a 1:1 ratio to receive either the Xarelto vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily; n = 3,286) or aspirin alone (100 mg once daily; n = 3,278). Patients were stratified by revascularization procedure type (endovascular vs surgical) and use of clopidogrel, which was administered at the treating physician’s discretion. Patients were followed for a median of 28 months.

The company noted that the VOYAGER PAD study met its primary efficacy and principal safety endpoints, demonstrating the Xarelto vascular dose was superior to aspirin alone in reducing the risk of major adverse limb and cardiovascular events (composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or cardiovascular death) by 15% in patients with symptomatic PAD after LER.

Additionally, the benefit of adding Xarelto to aspirin was apparent early, was consistent among major subgroups, and continued to accrue over time. There was no significant increase in thrombolysis in myocardial infarction major bleeding observed in patients treated with the Xarelto vascular dose compared to aspirin alone (Kaplan-Meier estimate at 3 years, 2.65% vs 1.87%).

In August 2021, the company announced FDA approval of an expanded PAD indication for the Xarelto vascular dose to include patients after undergoing a recent LER because of symptomatic PAD. The Xarelto vascular dose acts on a dual pathway inhibition approach to target clotting mechanisms, thrombin, and platelet activation, noted the company.