Reviwer: Dr. Örsan Deniz URGUN

Trial: Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease - VOYAGER PAD

Published in Congress: ACC 2021

Full Text Link: https://www.jacc.org/doi/abs/10.1016/j.jacc.2021.05.003

Background: Peripheral artery disease (PAD) patients undergoing lower extremity revascularization (LER) are at high risk for major adverse extremity and cardiovascular events. The benefit of rivaroxaban on total events in this population is unknown.

Objective : In this study, it was aimed to evaluate the total burden of vascular events and the safety of lower-dose rivaroxaban treatment and its effectiveness on total events in patients with peripheral artery disease who underwent lower extremity revascularization.

Method: This study is a multicenter randomized study, included 6564 patients over 50 years of age with a mean age of 67 who underwent successful lower extremity revascularization with a diagnosis of peripheral artery disease, and approximately two-thirds of the patients underwent endovascular revascularization and one-third surgical revascularization. They were randomized to rivaroxaban 2.5 mg+aspirin 100 mg (n:3286) and aspirin 100 mg (n:3278) twice daily and followed for a mean of 28 months. Of the patients, 26% were women, 40% were diagnosed with diabetes, and 32% had coronary artery disease. While 80% of the patients were using statins, 51% were using clopidogrel. The use of clopidogrel was left to the discretion of the doctor, while planned usage of aspirin and clopidogrel for more than 6 months, revascularized within 10 days, a history of acute extremity ischemia in the last 2 weeks, patients with acute coronary syndrome in the last 30 days, glomerular filtration rate value of <15 mL/min/1.73 m2, history of intracranial bleeding, history of stroke and transient ischemic attack were not included in the study. The primary efficacy outcome; acute limb ischemia, major amputation for vascular causes, nonfatal myocardial infarction, nonfatal ischemic stroke, or cardiovascular death.

Results: It was showed that rivaroxaban+aspirin treatment reduces primary events by 14% (p=0.02) and total vascular events (peripheral revascularization and venous thromboembolic events) by 14% (p=0.003) in the rivaroxaban+aspirin group. Treatment with rivaroxaban for every 100 patients enrolled in the study prevented 4.4 primary endpoint events and 12.5 vascular events over three years. At a mean follow-up of 28 months, the incidence of the first endpoint was 17.3% in the rivarksaban+aspirin group and 19.9% in the aspirin-only group (HR 0.85; 95% CI 0.76-0.96 p=0.009).
TIMI major bleeding was 2.65% in the rivaroxaban group and 1.87% in the placebo group (HR 1.43, 0.97-2.10, p=0.07). The International Society on Thrombosis and Haemostasis (ISTH), major bleeding was 5.94% in the rivaroxaban group and 4.06% in the placebo group (HR 1.42, 1.10-1.84, p=0.007).

Conclusion: In patients undergoing lower extremity revascularization, rivaroxaban treatment with aspirin was found to be superior in preventing major extremity and cardiovascular events compared to aspirin treatment alone, while a statistically insignificant tendency to increase in TIMI major bleeding and a significant increase in ISTH major bleeding was observed.

Interpretation: Patients with PAD who underwent LER are at greater risk for acute lower extremity ischemia than patients without LER.
The optimal antithrombotic therapy after successful revascularization is still unclear.
Patients with high ischemic burden will benefit most from high dose antiplatelet therapy.