Rivaroxaban reduces acute limb ischemia, but increases major bleeds after revascularization for PAD (VOYAGER PAD)

Référence

Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med 2020;382(21):1994-2004.

Sommaire

These investigators identified 6564 patients with symptomatic peripheral arterial disease who had undergone revascularization. The patients were randomized to receive rivaroxaban 2.5 mg twice daily or matching placebo. All patients also received aspirin 100 mg and approximately half were taking clopidogrel; two-thirds had undergone an endovascular procedure and one-third had open surgery. The patients' median age was 67 years, 74% were men, and less than 3% were Black. Groups were balanced at baseline and analysis was by intention to treat. Patients were followed up for a median of 28 months. The primary outcome was a composite of 5 (five!) things: acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, and death from cardiovascular causes. The composite outcome was less likely in the rivaroxaban group (15.5% vs 17.8%; P = .009; number needed to treat [NNT] = 44). This was driven primarily by less acute limb ischemia (4.7% vs 6.9%; P < .05; NNT = 46). There was no clinically or statistically significant difference in the other 4 outcomes, and there were numerically more cardiovascular deaths in the rivaroxaban group (6.1% vs 5.3%; HR 1.14; 95% CI 0.93 - 1.40). There was significantly more bleeding in the rivaroxaban group. The bleeding was or wasn't statistically significant depending on how you define it – for example, there was more major bleeding in the rivaroxaban group using the International Society on Thrombosis and Haemostasis definition (4.3% vs 3.1%; P = .007; number needed to treat to harm = 83) -- but the bleeding was clinically signficant by every definition. Death from any cause was higher in the rivaroxaban group, but this difference was not statistically significant (9.8% vs 9.1%). Fortunately, there was no difference in the likelihood of fatal or intracranial bleeding (17 vs 19 events).