Introduction and methods

The VOYAGER PAD (Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularizations for Peripheral Artery Disease) Trial

Presented at ACC.20 by Marc P. Bonaca (Aurora, CO, US)

Patients with lower extremity peripheral artery disease (PAD) frequently develop limb symptoms, which are treated with revascularization therapy. However, after revascularization, acute limb ischemia may develop which is associated with long hospitalizations and high incidences of limb loss, disability and death. Medical therapy for prevention of major adverse CV events (MACE) and major adverse limb events (MALE) after revascularization has not been defined and no class I recommendations for medical therapy exists. The COMPASS trial demonstrated that low dose rivaroxaban with aspirin reduces MACE and MALE in patients with chronic stable PAD compared to aspirin alone.

The VOYAGER PAD (Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) trial tested whether low dose rivaroxaban reduced primary efficacy outcome in PAD patients, defined as a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from CV causes. In addition, safety of rivaroxaban was assessed by TIMI major bleeding.. Included were 6564 patients (age ≥50 years) with lower extremity PAD undergoing acute peripheral revascularization for ischemia, randomized to 2.5 mg rivaroxaban twice daily (n=3286) or placebo (n=3278), added to background aspirin therapy. Median follow-up was 28 months.

Main results

• Incidence of primary efficacy outcome at 3 years was 17.3% for rivaroxaban and 19.9% for placebo (HR 0.85, 95% CI: 0.76-0.96; P=0.0085).

• Secondary outcomes of a composite of MI, ischemic stroke, coronary heart disease (CHD), acute limb ischemia (ALI), amputation, a composite of unplanned limb revascularization for ischemia, a composite of vascular hospitalization for a coronary or peripheral thrombotic event, a composite of MI, ischemic stroke, ALI, amputation, all-cause death, a composite of MI, all stroke, CV death, ALI, amputation were all significantly reduced in the rivaroxaban group compared to the placebo group. Mortality and VTE were not different between the two treatment groups.

• Incidence of TIMI major bleeding at 3 years was 2.65% for rivaroxaban and 1.87% for placebo (HR 1.43, 95% CI: 0.97-2.10; P=0.07). No difference in ICH and fatal bleeding were observed between the two treatment groups.

• Incidence of ISTH major bleeding at 3 years was 5.94% for rivaroxaban and 4.06% for placebo (HR 1.42, 95% CI: 1.10-1.84; P=0.007). BARC 3b or greater was not significantly different between the two groups.

Conclusion

In PAD patients who had undergone lower-extremity revascularization, treatment with rivaroxaban 2.5 mg twice daily with aspirin as compared to aspirin alone significantly reduced risk of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from CV causes. TIMI major bleeding was numerically increased and incidence of ISTH major bleeding was significantly higher after rivaroxaban treatment, but no difference in ICH and fatal bleeding was observed with rivaroxaban and placebo.

- Our coverage of ACC.20 is based on the information provided during the congress –

The results were simultaneously published in NEJM