"Rivaroxaban in Peripheral Artery Disease after Revascularization (VOYAGER PAD Trial)". The New England Journal of Medicine. 2020.
Links to original sources: Wiki Journal Post Full Journal Article
Does the addition of rivaroxaban to aspirin improve outcomes in patients with peripheral artery disease (PAD) following lower-extremity revascularization?
In patients with PAD who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin significantly reduced the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes, compared to aspirin alone. However, rivaroxaban increased the risk of major bleeding as defined by ISTH.
The VOYAGER PAD trial showed that rivaroxaban, in combination with aspirin, provided a net clinical benefit in patients after lower-extremity revascularization for PAD, despite an increased bleeding risk. This strategy could lead to a change in practice, as monotherapy with aspirin or clopidogrel has been the standard.
Current guidelines recommend aspirin or clopidogrel monotherapy for patients with symptomatic PAD. The results of this trial may influence future recommendations for antithrombotic therapy following PAD revascularization.
- Multicenter, double-blind, parallel-group, placebo-controlled, randomized trial - N=6,564 patients with symptomatic PAD having undergone lower-extremity revascularization - Randomized to rivaroxaban 2.5mg PO BID (n=3,286) or placebo (n=3,278), both plus aspirin 100mg daily - Enrollment: 2015-2018 - Mean follow-up: 28 months - Analysis: Intention-to-treat for efficacy; on-treatment for safety outcomes - Primary efficacy outcome: Composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes - Primary safety outcome: Major bleeding as per TIMI classification
- Inclusion Criteria: Patients ≥50 years old with PAD, having undergone successful revascularization ≤10 days prior for symptomatic PAD - Exclusion Criteria: Clinically unstable patients, heightened risk for bleeding, or on prohibited concurrent medications (long-term clopidogrel, etc.) - Baseline Characteristics: Median age 67, 26% women, 40% with diabetes, 35% current smokers, 65% treated endovascularly, 35% surgically
- Rivaroxaban 2.5mg twice daily plus aspirin 100mg daily - Placebo plus aspirin 100mg daily
- Primary efficacy outcome occurred in 17.3% with rivaroxaban versus 19.9% with placebo at 3 years (HR 0.85; 95% CI, 0.76-0.96; P=0.009) - TIMI major bleeding: 2.65% with rivaroxaban versus 1.87% with placebo (HR 1.43; P=0.07) - ISTH major bleeding: 5.94% with rivaroxaban versus 4.06% with placebo (HR 1.42; P=0.007)
High rate of treatment discontinuation may have attenuated the benefits observed in the intention-to-treat analysis.
The trial was supported by Bayer and Janssen Pharmaceuticals.
Detailed trial information and associated editorials can be found on the NEJM website and within the journal's publication.