Rivaroxaban should be considered as adjunctive therapy to aspirin alone in patients undergoing peripheral limb revascularization, authors of the VOYAGER-PAD trial concluded today. In the Late Breaking Clinical Trials session earlier today at the 2021 American College of Cardiology Scientific Sessions, Dr. Rupert Bauersachs of Darmstadt, Germany, presented the anticipated results of the trial, which attempted to answer whether post-intervention rivaroxaban could prevent future limb ischemia and need for repeat revascularization.
The impetus for this study was the high rates of acute limb ischemia observed after lower extremity revascularization in prior peripheral intervention trials. In both PEGASUS and EUCLID, the risk of acute limb ischemia was three and four-fold higher after intervention, respectively.
In this double blinded, placebo-controlled randomized clinical trial, 6,564 participants undergoing peripheral intervention were randomized to receive either 2.5 mg of rivaroxaban twice daily, or placebo, in addition to the aspirin and/or P2Y12 inhibitor prescribed to them. Patients were enrolled if they had symptomatic peripheral artery disease with an ankle brachial index ≤ 0.8, or toe brachial index of ≤ 0.6, with anatomy of occlusive disease distal to the iliac arteries. The primary efficacy endpoint was acute limb ischemia, major amputation of vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was TIMI major bleeding. Coronary artery disease and diabetes were present at baseline in at least one-third of patients. 80% of participants were on a statin, and half were on clopidogrel. Two thirds of patients underwent endovascular intervention, and one-third were treated with surgical revascularization.
The primary efficacy endpoint was significantly lower in the rivaroxaban group (17.3% vs 19.9%, HR 0.85, 95% CI 0.76-0.96, p =0.0085). The secondary outcomes of unplanned limb revascularization and venous thromboembolism were also significantly lower in the rivaroxaban arm. While there were fewer TIMI major bleeding events in the placebo group, the difference was not found to be significant. The investigators went further to assess the effect of rivaroxaban on total vascular events, and found that the benefit of rivaroxaban was amplified over time. While there were 61 fewer first vascular events in the rivaroxaban arm, there were 342 fewer events overall, showing that most of the benefit was observed after the primary outcome was met.
“I don’t think any of us would have imagined the level of morbidity that exists in this population,” said Dr. Joshua Beckman of Vanderbilt University in response to the trial’s results, “I think studies like this make it clear that there is an association of events between vascular beds, and that specific pharmacologic therapies need to be tailored within vascular beds”.
The study results were published simultaneously in the Journal of the American College of Cardiology.