Rivaroxaban and Aspirin Dual Therapy for Peripheral Artery Disease

A meta-analysis of COMPASS and VOYAGER compared low-dose rivaroxaban and aspirin vs aspirin alone across a broad spectrum of patients with PAD.

A systematic review and meta-analysis found that low-dose rivaroxaban with aspirin was more effective than aspirin alone for reducing major cardiovascular (CV) events and limb outcomes among patients with peripheral artery disease (PAD). Findings of the review were recently published in the European Journal of Preventive Cardiology,

The analysis combined data from 2 clinical trials, COMPASS (ClinicalTrials.gov Identifier: NCT01776424) and VOYAGER (ClinicalTrials.gov Identifier: NCT02504216). Patients (n=11,560) with PAD were assessed for CV outcomes following dual therapy with rivaroxaban 2.5 mg twice daily and aspirin (n=5778) or monotherapy with aspirin 100 mg (n=5782) up to a median of 21 months (COMPASS) or 28 months (VOYAGER).

Participants in the COMPASS and VOYAGER trials were 28.7% and 25.9% women, respectively, with a median age of 68 (interquartile range [IQR], 63-74) and 67 (IQR, 61-73) years, respectively.

Dual therapy with rivaroxaban and aspirin was associated with reduced risk for the composite endpoints of myocardial infarction (MI), ischemic stroke, CV death, acute limb ischemia, or major vascular amputation (hazard ratio [HR], 0.79; 95% CI, 0.65-0.95; P =.012) and acute limb ischemia or major vascular amputation (HR, 0.68; 95% CI, 0.52-0.90; P =.007) but not for MI, ischemic stroke, or CV death (HR, 0.85; 95% CI, 0.65-1.13; P =.26).

Heterogeneity for composite comparisons ranged from moderate (I2, 33%; P =.22) to high (I2, 75.8%; P =.04).

Similar results were observed among symptomatic patients with PAD (n=2768) who had recently undergone revascularization (COMPASS).

Major bleeding was more effectively reduced with aspirin monotherapy (HR, 1.51; 95% CI, 1.22-1.87; P =.0002), equating to an increase of 0.6% per year in major bleeding events among dual therapy recipients.

Risk-benefit analysis found that for every 1000 patients with PAD treated, dual therapy prevented 12 major CV or limb events but caused 5 major nonfatal bleeds and 1 fatal or critical organ bleed. For symptomatic PAD, dual therapy prevented 13 major CV or limb events but caused 7 nonfatal bleeds and 1 fatal or critical organ bleed.

This study was limited by the low number of events within the patient population studied, the authors noted.

“Among patients with PAD, low-dose rivaroxaban plus aspirin is superior to aspirin alone in reducing CV and limb outcomes including acute limb ischaemia and major vascular amputation,” the researchers concluded. “This is offset by an increase in major bleeding, but no excess of severe bleeding,” they added.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Anand SS, Hiatt W, Dyal L, et al. Low-dose rivaroxaban and aspirin among patients with peripheral artery disease: a meta-analysis of the COMPASS and VOYAGER trials. Eur J Prev Cardiol. Published online August 31, 2021. doi:10.1093/eurjpc/zwab128