Rivaroxaban plus aspirin reduces adverse limb and CV events in PAD patients undergoing revascularization

Rivaroxaban plus aspirin is effective in lowering the incidence of major adverse limb and cardiovascular (CV) events in patients with peripheral artery disease (PAD) undergoing lower-extremity revascularization, according to results of the VOYAGER-PAD trial presented at the American College of Cardiology and World Congress of Cardiology 2020 virtual meeting (ACC.20/WCC).

“In symptomatic PAD patients after revascularization, rivaroxaban 2.5 mg BID with aspirin, compared with aspirin alone, significantly reduced the incidence of vascular outcomes. The benefits of the combination regimen were apparent early and consistent over time, and the need for unplanned index limb revascularization was reduced,” said investigator Professor Marc Bonaca from the University of Colorado School of Medicine in Aurora, Colorado, US. [Bonaca M, et al, ACC.20/WCC, abstract 402-10; N Engl J Med 2020, doi: 10.1056/NEJMoa2000052]

In the multicenter VOYAGER-PAD trial, 6,564 patients (median age, 67 years; male, 74 percent) with lower extremity PAD undergoing revascularization were randomized (1:1) to receive rivaroxaban 2.5 mg BID plus aspirin or placebo plus aspirin.

Risk factors of hypertension (81 percent), hyperlipidaemia (60 percent) and diabetes mellitus (DM; 40 percent) were common at baseline. In terms of PAD history, most patients (95 percent) had claudication and the median ankle-brachial index was 0.56. Revascularization was indicated as a result of claudication and critical limb ischaemia in 77 percent and 23 percent of the patients, respectively.

At a median follow-up of 28 months, the risk of the primary composite outcome (acute limb ischaemia, major amputation for vascular causes, myocardial infarction, ischaemic stroke or CV death) was significantly reduced with rivaroxaban-aspirin vs placebo-aspirin (17.3 percent vs 19.9 percent; hazard ratio [HR], 0.85; 95 percent confidence interval [CI], 0.76 to 0.96; p=0.009).

Rivaroxaban-aspirin also significantly reduced the risks of five of the seven secondary efficacy outcomes, including unplanned index limb revascularization (20.0 percent vs 22.5 percent; HR, 0.88; 95 CI, 0.79 to 0.99; p=0.028), compared with placebo-aspirin. No significant reduction was shown in the secondary outcomes of all-cause mortality and venous thromboembolism.

Consistent benefit of rivaroxaban plus aspirin for the primary outcome was demonstrated in patients aged <75 years (HR, 0.86; 95 percent CI, 0.75 to 0.98), male (HR, 0.82; 95 percent CI, 0.71 to 0.94), and those with a history of coronary artery disease (HR, 0.78; 95 percent CI, 0.64 to 0.95) as compared with aspirin alone.

The incidence of thrombolysis in myocardial infarction (TIMI) major bleeding was similar between the rivaroxaban-aspirin and placebo-aspirin groups (2.7 percent vs 1.9 percent; HR, 1.43; 95 percent CI, 0.97 to 2.10; p=0.07). Likewise, there was no significant between-group difference in the incidence of intracranial bleeding (0.6 percent vs 0.9 percent; HR, 0.78; 95 percent CI, 0.38 to 1.61; p=0.50) and fatal bleeding (0.2 percent vs 0.2 percent). International Society on Thrombosis and Haemostasis (ISTH) major bleeding, on the other hand, occurred at a significantly higher rate with rivaroxaban-aspirin vs placebo-aspirin (5.9 percent vs 4.1 percent; HR, 1.42; 95 percent CI, 1.10 to 1.84; p=0.007).