Phase III VOYAGER PAD study of Xarelto meets primary endpoints in symptomatic peripheral artery disease.- Janssen

The Janssen Pharmaceutical Companies of Johnson & Johnson announced the VOYAGER PAD study met its primary efficacy and principal safety endpoints, demonstrating the Xarelto (rivaroxaban) vascular dose (2.5 mg twice daily) plus aspirin (100 mg once daily) was superior to aspirin alone in reducing the risk of major adverse limb and cardiovascular (CV) events by 15 percent in patients with symptomatic peripheral artery disease (PAD) after lower-extremity revascularization, with similar rates of TIMI1 major bleeding. VOYAGER PAD is the only study to show a significant benefit using dual pathway inhibition, an anticoagulant plus aspirin, in this patient population. For the primary efficacy endpoint, Xarelto plus aspirin significantly reduced the risk of major adverse limb and CV events compared to aspirin alone. Specifically, researchers observed that nearly one in five patients taking aspirin alone suffered a major adverse limb or CV event, but this risk was significantly reduced by 15 percent when Xarelto was added. The Kaplan-Meier (KM) estimates of the incidence at three years for Xarelto /aspirin compared to aspirin alone were 17.3% vs. 19.9%, respectively (Hazard Ratio [HR]=0.85; 95% confidence interval [CI], 0.76-0.96; p=0.009). The benefit of adding Xarelto to aspirin was apparent early, was consistent among major subgroups and continued to accrue over time. The principal safety endpoint was met, with no significant increase in TIMI major bleeding in patients treated with Xarelto plus aspirin compared to aspirin alone. The KM estimates of the incidence at three years for Xarelto /aspirin compared to aspirin alone were 2.65% vs. 1.87%, respectively (HR=1.43; 95% CI, 0.97–2.10; p=0.07). Of note, there were numerically fewer intracranial bleeding events in the Xarelto /aspirin group (0.60% vs. 0.90%; HR=0.78; 95% CI, 0.38–1.61) and no increase in fatal bleeding (0.21% vs. 0.21%; HR=1.02; 95% CI, 0.33–3.15) across both groups. Findings from this global, randomized, double-blind, Phase III study were presented as a late-breaking presentation during the virtual American College of Cardiology's 69th Annual Scientific Session, together with the World Congress of Cardiology (ACC.20/WCC), and simultaneously published in The New England Journal of Medicine.See: Rivaroxaban in Peripheral Artery Disease after Revascularization. Marc P. Bonaca et al. New England Journal of Medicine March 28, 2020 DOI: 10.1056/NEJMoa2000052.