Janssen announced positive results from the phase 3 VOYAGER PAD study evaluating rivaroxaban (Xarelto) in patients with symptomatic peripheral artery disease (PAD) who had undergone peripheral revascularization procedures of the lower extremities.
The multicenter, double-blind, placebo-controlled study included 6564 patients who were randomized to receive rivaroxaban 2.5mg twice daily plus aspirin (n=3286) or placebo plus aspirin (n=3278). The primary efficacy end point was a composite of major adverse limb and cardiovascular (CV) events, including myocardial infarction, ischemic stroke, CV death, acute limb ischemia, and major amputation for vascular causes. The primary safety end point was major bleeding, defined according to the Thrombolysis in Myocardial Infarction (TIMI) classification. A key secondary end point included major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH).
Findings from the study showed that treatment with rivaroxaban plus aspirin significantly reduced the risk of major adverse limb and CV events; Kaplan-Meier estimates of the incidence at 3 years were 17.5% and 19.9%, respectively (HR 0.85; 95% CI, 0.76-0.96; P =.009). The incidence of TIMI major bleeding did not differ significantly between rivaroxaban and placebo (2.65% [n=62] vs 1.87% [n=44], respectively; HR 1.43; 95% CI, 0.97-2.10; P =.07). A significantly higher incidence of ISTH major bleeding occurred in patients treated with rivaroxaban compared with placebo (5.94% [n=140] vs 4.06% [n=100], respectively; HR 1.42; 95% CI, 1.10-1.84; P =.007).
The results of the VOYAGER PAD study support the findings from the phase 3 COMPASS study, which found rivaroxaban plus aspirin reduced the risk of major CV and limb events in patients with stable PAD and/or coronary artery disease compared with aspirin alone. Full study data from VOYAGER PAD were presented during the virtual American College of Cardiology’s 69th Annual Scientific Session, together with the World Congress of Cardiology (ACC.20/WCC), and published in The New England Journal of Medicine.
“While the COMPASS trial established the efficacy of rivaroxaban plus aspirin in stable patients with PAD and coronary artery disease (CAD), there were important unanswered questions on the optimal strategy for patients with symptomatic PAD after lower extremity revascularization, including those without CAD,” said Marc P. Bonaca, MD, Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. “The VOYAGER PAD study shows us the potential clinical utility of rivaroxaban 2.5mg twice daily plus aspirin in preventing the most critical thrombotic complications, adverse limb and cardiovascular outcomes, during the post-revascularization period when PAD patients are most vulnerable to these serious events.”
Xarelto, a Factor Xa inhibitor, is currently indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, and for use in combination with aspirin, to reduce the risk of major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in patients with chronic coronary artery disease or peripheral artery disease. It is also approved to treat deep vein thrombosis (DVT) and pulmonary embolism (PE), for the reduction of the risk of recurrent DVT/PE, and for primary prevention of DVT, which may lead to PE, in patients who have just had hip or knee replacement.
Xarelto is also approved for the prophylaxis of venous thromboembolism (VTE) and VTE-related death during hospitalization and post hospital discharge in adult patients admitted for an acute medical illness who are at risk for thromboembolic complications due to moderate or severe restricted mobility and other risk factors for VTE and not at high risk of bleeding.