What clinical trial found Xarelto (rivaroxaban) 2.5 mg twice a day useful in severe Peripheral Artery Disease (PAD)?

From the Guidelines

The clinical trial that found Xarelto (rivaroxaban) 2.5 mg twice a day useful in severe Peripheral Artery Disease (PAD) is the VOYAGER PAD trial.

Key Findings

• The VOYAGER PAD trial assessed a regimen of low-dose rivaroxaban (2.5 mg twice daily) in addition to low-dose aspirin in patients within 10 days of lower extremity revascularization who were not on anticoagulation for another indication or had planned P2Y12 receptor antagonist use 1.
• The trial found that the combination of low-dose rivaroxaban and low-dose aspirin reduced the risk of a composite endpoint of MACE and MALE compared with aspirin alone, mainly driven by lower rates of ALI 1.
• The use of rivaroxaban 2.5 mg twice daily plus aspirin was also associated with a significantly lower incidence of ischemic cardiovascular events, including major adverse limb events, in the VOYAGER PAD trial 1.

Clinical Guidelines

• The 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease recommends the use of low-dose rivaroxaban (2.5 mg twice daily) combined with low-dose aspirin to reduce the risk of MACE and MALE in patients with symptomatic PAD after endovascular or surgical revascularization 1.
• The guideline also recommends the use of single antiplatelet therapy, such as aspirin, in patients with asymptomatic PAD to reduce the risk of MACE 1.

Important Considerations

• The use of dual antiplatelet therapy or antiplatelet plus anticoagulant treatment strategies should be thoroughly discussed with eligible individuals, and shared decision-making should be used to determine an individually appropriate treatment approach 1.
• The risks and benefits of these treatment strategies should be carefully weighed, taking into account the increased risk of major bleeding associated with the use of rivaroxaban plus aspirin 1.

From the FDA Drug Label

The efficacy and safety of XARELTO 2.5 mg orally twice daily versus placebo on a background of aspirin 100 mg once daily in patients with PAD were evaluated in the COMPASS study (n=4996) and will be referred to as the COMPASS PAD population A total of 6,564 patients were equally randomized to XARELTO 2.5 mg orally twice daily vs placebo on a background therapy of aspirin 100 mg once daily in the double-blinded, placebo-controlled Vascular Outcomes studY of ASA alonG with rivaroxaban in Endovascular or surgical limb Revascularization for peripheral artery disease (PAD) trial (VOYAGER)

The clinical trials that found Xarelto (rivaroxaban) 2.5 mg twice a day useful in severe Peripheral Artery Disease (PAD) are the COMPASS and VOYAGER trials 2.

From the Research

Clinical Trial Overview

The clinical trial that found Xarelto (rivaroxaban) 2.5 mg twice a day useful in severe Peripheral Artery Disease (PAD) is the VOYAGER PAD trial.

Key Findings

• The VOYAGER PAD trial demonstrated that rivaroxaban 2.5 mg twice daily plus aspirin reduced the risk of major cardiac and ischemic limb events after lower extremity revascularization 3, 4, 5, 6.
• The trial showed that rivaroxaban reduced the primary efficacy outcome, which was a composite of acute limb ischemia, major amputation of a vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death 3, 4, 5, 6.
• The results also indicated that rivaroxaban increased the risk of major bleeding, but the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention 3, 4, 5, 6.

Patient Population

• The VOYAGER PAD trial included patients with symptomatic peripheral artery disease who underwent lower extremity revascularization, either through endovascular or surgical methods 3, 4, 5, 6.
• The trial also included a subgroup of patients who were categorized as fragile, based on prespecified criteria such as age, weight, and baseline estimated glomerular filtration rate 3.

Treatment Regimen

• The treatment regimen consisted of rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily, compared to aspirin alone or rivaroxaban placebo plus aspirin 3, 4, 5, 6.
• The use of concomitant clopidogrel was allowed at the discretion of the investigator for up to 6 months after the qualifying revascularization 6.

Comparison to Other Studies

• Another study, published in the Lancet, also found that low-dose rivaroxaban plus aspirin reduced major adverse cardiovascular and limb events in patients with stable peripheral or carotid artery disease, compared to aspirin alone 7.
• This study used a similar treatment regimen, with rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily, and found that the combination therapy reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke, as well as major adverse limb events including major amputation 7.