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evident
Original paper
2020NEJMCardiology

VOYAGER PAD

Rivaroxaban in peripheral artery disease after revascularization

RCTPeripheral artery disease

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Overview

Low-dose rivaroxaban plus aspirin reduced limb and cardiovascular events after PAD revascularization.

Clinical takeaway

VOYAGER PAD supports dual-pathway inhibition after lower-extremity revascularization in selected PAD patients, balancing ischemic benefit against bleeding.

Key result

The composite of acute limb ischemia, major amputation, MI, ischemic stroke, or CV death was reduced (3-year incidence 17.3% vs 19.9%; HR 0.85, 95% CI 0.76-0.96).

Practice impact

Consider rivaroxaban 2.5 mg twice daily plus aspirin after PAD revascularization when bleeding risk is acceptable.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

6,564

Follow-up

Median 28 months.

Geography

Multinational

Clinical question

Does low-dose rivaroxaban plus aspirin reduce limb and cardiovascular events after lower-extremity revascularization for PAD?

Population

  • Patients with symptomatic lower-extremity PAD after surgical or endovascular revascularization.

Intervention

Rivaroxaban 2.5 mg twice daily plus aspirin.

Comparator

Placebo plus aspirin.

Primary outcome

Composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death.

Rivaroxaban plus aspirin reduced major limb and cardiovascular events after PAD revascularization.

Hazard ratio / 0.85 / 95% CI 0.76-0.96 / p=0.009

Key results

  • Primary composite was reduced with rivaroxaban plus aspirin: 508 vs 584 events; 3-year Kaplan-Meier incidence 17.3% vs 19.9%; HR 0.85 (95% CI 0.76-0.96; p=0.009).
  • Acute limb ischemia was reduced.
  • TIMI major bleeding (principal safety outcome) did not differ significantly: 2.65% vs 1.87%; HR 1.43 (95% CI 0.97-2.10; p=0.07).
  • ISTH major bleeding (secondary safety outcome) was increased: 5.94% vs 4.06%; HR 1.42 (95% CI 1.10-1.84; p=0.007).

Harms

  • ISTH major bleeding was increased (5.94% vs 4.06%; HR 1.42, 95% CI 1.10-1.84); TIMI major bleeding, the principal safety outcome, was not significantly increased (2.65% vs 1.87%; HR 1.43, 95% CI 0.97-2.10).
  • Bleeding-risk selection is essential.

Clinical Use

Practice impact

  • Extended dual-pathway inhibition evidence into post-revascularization PAD care.

Applicability

  • Symptomatic PAD patients after lower-extremity revascularization with acceptable bleeding risk.

Limitations

  • Not for patients requiring full-dose anticoagulation or with high bleeding risk.
  • Requires coordination across vascular surgery, cardiology, and primary care.

Common misinterpretations

  • The trial used vascular-dose rivaroxaban, not full-dose AF/VTE anticoagulation.

Related evidence

COMPASS - Same Drug Class

Citation

Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in Peripheral Artery Disease after Revascularization. N Engl J Med. 2020;382(21):1994-2004. doi:10.1056/NEJMoa2000052

The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and in 584 in the placebo group; the Kaplan-Meier estimates of the incidence at 3 years were 17.3% and 19.9%, respectively (hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P = 0.009).