Efficacy and Safety of Rivaroxaban in Patients with Peripheral Artery Disease: A GRADE-assessed Systematic Review and Meta-Analysis.
OBJECTIVES Peripheral artery disease (PAD) is a common atherosclerotic disorder characterized by progressive arterial narrowing in the limbs. This study aims to determine the efficacy and safety of rivaroxaban, focusing on major cardiovascular events, limb outcomes, and bleeding risks. METHODS PubMed, Cochrane, and EMBASE were searched for RCTs and non-randomized comparative studies that compared rivaroxaban, either alone or in combination with aspirin, to placebo or standard care such as antiplatelet therapy. Risk ratios and hazard ratios with 95% confidence intervals were pooled using R v4.5.1 with an appropriate random-effects model applied. Subgroup analyses were performed according to rivaroxaban plus aspirin versus rivaroxaban alone. RESULTS 39,991 participants across six studies were included. Compared with control, use of rivaroxaban was linked to a significant reduction in composite efficacy outcomes (RR= 0.84, 95%CI 0.78-0.91, p<0.001), risk of acute limb ischemia (RR= 0.65, 95% CI 0.55-0.78, p<0.001), and thromboembolism (RR= 0.60, 95% CI 0.38-0.97, p=0.037). Although rivaroxaban plus aspirin failed to show a significant reduction in the risk of amputation, rivaroxaban alone reported a significant risk reduction (RR=0.50, 95% CI 0.30-0.85, p=0.003). However, its use was associated with a significantly higher risk of major bleeding (HR=1.54, 95% CI 1.38-1.72, p<0.001) and International Society of Thrombosis and Hemostasis-defined bleeding (RR= 1.45, 95% CI 1.19-1.76, p<0.001). No significant differences were observed for stroke, myocardial infarction, major adverse limb events, fatal bleeding, mortality, or cardiovascular mortality. CONCLUSION Rivaroxaban-based therapy reduced the trial-defined composite efficacy outcome, acute limb ischemia, and thromboembolism in patients with PAD, but increased the risk of major bleeding. These findings support individualized use of rivaroxaban-based therapy in carefully selected patients, balancing ischemic and limb-protective benefits against bleeding risk.