The Food and Drug Administration has expanded the approval for Xarelto® (rivaroxaban) in combination with aspirin to reduce the risk of major thrombotic vascular events in patients with peripheral artery disease (PAD), including patients who have recently undergone a lower extremity revascularization procedure due to symptomatic PAD.
The approval was based on data from the double-blind, placebo-controlled phase 3 VOYAGER PAD study (ClinicalTrials.gov Identifier: NCT02504216) that assessed the efficacy and safety of rivaroxaban, a factor Xa inhibitor, in 6564 patients aged 50 years and older with symptomatic PAD after lower extremity revascularization procedures. Patients were randomly assigned 1:1 to receive rivaroxaban 2.5mg twice daily plus aspirin or placebo plus aspirin.
The primary efficacy endpoint of the study was the time to first occurrence of major thrombotic vascular events: myocardial infarction, ischemic stroke, acute limb ischemia, major amputation, or death from cardiovascular (CV) causes; the primary safety endpoint was the time to first occurrence of major bleeding events according to the Thrombolysis in Myocardial Infarction (TIMI) classification.
Findings from the study showed that treatment with rivaroxaban plus aspirin significantly reduced the risk of major thrombotic vascular events with an event rate per year of 6.8% compared with 8.0% for placebo (hazard ratio 0.85; 95% CI, 0.76-0.96; P =.0085). 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).
Compared with placebo during 10,000 patient-years of treatment, rivaroxaban would be expected to result in 181 fewer primary outcome events and 29 more TIMI major bleeding events, indicating a favorable balance of benefits and risks.
Xarelto is already 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 CV events (CV death, myocardial infarction, and stroke) in patients with chronic coronary artery disease or PAD. 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 indicated 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.
- FDA approves expanded peripheral artery disease (PAD) Indication for Xarelto® (rivaroxaban) plus aspirin to include patients after lower-extremity revascularization (LER) due to symptomatic PAD. News release. Janssen Pharmaceuticals, Inc. Accessed August 24, 2021. https://www.prnewswire.com/news-releases/fda-approves-expanded-peripheral-artery-disease-pad-indication-for-xarelto-rivaroxaban-plus-aspirin-to-include-patients-after-lower-extremity-revascularization-ler-due-to-symptomatic-pad-301361537.html.
- Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021.