A supplemental New Drug Application (sNDA) for rivaroxaban (Xarelto®; Janssen) to reduce the risk of major thrombotic vascular events in patients with peripheral artery disease (PAD) has been submitted to the Food and Drug Administration (FDA).

The application is supported by data from the double-blind, placebo-controlled phase 3 VOYAGER PAD trial 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 randomized 1:1 to receive rivaroxaban 2.5mg twice daily plus aspirin or placebo plus aspirin.

The primary efficacy end point 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 end point 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 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).

“Various antithrombotic regimens have been evaluated for short- and long-term prevention of major vascular events in patients with PAD, but only rivaroxaban in combination with aspirin has demonstrated a significant benefit over aspirin alone,” said James List, MD, PhD, Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC. “Data from the VOYAGER PAD trial were the first in 20 years to show clinical benefit with an antithrombotic therapy in the symptomatic PAD population after lower-extremity revascularization, which speaks to the need for a new treatment in this space.”

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Xarelto 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 CV events (CV 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.

For more information visit janssen.com.


  1. Janssen submits application to US FDA for new indication to expand use of Xarelto® (rivaroxaban) in patients with peripheral artery disease. [press release]. Raritan, NJ: Janssen Pharmaceutical Companies; October 26, 2020. 
  2. Landmark phase 3 VOYAGER PAD study of Xarelto® (rivaroxaban) plus aspirin shows significant benefit in patients with symptomatic peripheral artery disease (PAD) after lower-extremity revascularization. [press release]. Raritan, NJ: Janssen Pharmaceutical Companies; March 28, 2020.
  3. Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med. Published online May 21, 2020. doi: 10.1056/NEJMoa2000052.