Abstract
BACKGROUND: VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) demonstrated that antiplatelet therapy with rivaroxaban 2.5 mg twice daily compared with placebo reduced the first event in a composite end point in patients with peripheral artery disease after revascularization. The purpose of this analysis was to (1) evaluate whether rivaroxaban decreased the most severe events and (2) compare the harm and benefit of rivaroxaban on the same scale. METHODS: Two exploratory, hierarchical analyses of the primary efficacy composite outcome and one exploratory analysis of the net clinical benefit composite outcome were prespecified. The global rank method and the win ratio method ranked components of the composite outcome by clinical importance. The net clinical benefit included both efficacy and safety outcomes. RESULTS: The global rank method demonstrated that participants on rivaroxaban had fewer or later events than their placebo counterparts when events were compared in a hierarchical manner (primary ranking, P=0.0158). The win ratio approach demonstrated fewer or later fatal and nonfatal ischemic events in the rivaroxaban arm (win ratio, 1.16 [95% CI, 1.03-1.30]; P=0.0167). The net clinical benefit analysis revealed an overall beneficial effect of rivaroxaban when different efficacy and safety end points were included (P<0.001). CONCLUSIONS: Evaluation of the VOYAGER PAD primary outcome exploring ranking of components revealed that (1) rivaroxaban decreased the most severe ischemic events and (2) that across different efficacy and safety outcomes, results consistently supported a favorable benefit-risk profile. These results help inform shared decision making on the use of rivaroxaban 2.5 mg twice daily with daily antiplatelet therapy. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT02504216.