Aspirin Plus Rivaroxaban vs Aspirin Alone: Improvement of Claudication, Limb Pain and Ankle-Brachial Index in Diabetic Peripheral Arterial Disease (PAD) Before Revascularization: A Clinical Randomized Trial

Background: Peripheral artery disease (PAD) is a condition characterized by the occlusion of non-cardiac, non-intracranial peripheral arteries, which may result in reduced blood flow or tissue damage. The PAD is a common complication of type 2 diabetes mellitus. Aspirin (ASA) is the most commonly used antiplatelet medication in chronic stable PAD patients, and other medications are being tested to improve the efficacy of ASA. Objectives: This study aims to compare the effects of ASA monotherapy versus ASA and rivaroxaban dual therapy in improving the signs and symptoms of PAD. Methods: This is an open-label randomized controlled trial. Sixty type 2 diabetic patients with symptomatic PAD of the lower limbs were randomly divided into two groups using a computer-generated randomization schedule prepared before the study. In group A, thirty patients received rivaroxaban 2.5 mg twice a day and ASA 100 mg daily, while in group B, thirty patients received ASA 100 mg daily (initiated or continued at randomization) for 12 weeks. Intermittent claudication (IC), limb pain at rest/overnight, and Ankle-Brachial Index (ABI) were evaluated in patients before and after medication. The Wilcoxon test was used to compare values before and after treatment in each group, and the chi-square and Fisher Exact test were used to compare between groups. A P-value less than 0.05 was considered statistically significant. Results: Thirty patients were enrolled in each group and had similar baseline characteristics, with no significant differences in age, sex, smoking condition, and BMI (P-values of 0.87, 0.302, 0.95, and 0.448, respectively). After treatment, group A had lower rates of severe IC (33.3% vs 66.7%; P = 0.011), lower rates of rest pain (33.3% vs 70.0%; P = 0.009), and no cases of severe ABI (0.0% vs 23.3%; P = 0.001) compared to group B. Additionally, in group A, IC was completely resolved in one patient, and ABI was normalized in six patients after treatment. There was no incidence of bleeding and/or major adverse limb events. Conclusions: Our findings suggest that the combination of rivaroxaban and ASA is more potent than ASA alone for the treatment of PAD features, including IC, limb pain at rest/overnight, and ABI before revascularization therapy.