Antiplatelet and Anticoagulation Therapy for Peripheral Arterial Disease: Risks Versus Benefits

Peripheral arterial disease (PAD) affects millions of people worldwide. It is a progressive atherosclerotic condition that ranges from asymptomatic disease to severe manifestations such as chronic limb-threatening ischemia and acute limb ischemia. Major risk factors-diabetes mellitus, smoking, hypertension, and hypercholesterolemia-contribute to its pathogenesis by promoting oxidative stress, endothelial dysfunction, and platelet activation. Optimizing antiplatelet and anticoagulant therapy is essential to reducing major adverse cardiovascular events and major adverse limb events. Aspirin and clopidogrel remain standard therapies, but recent trials such as COMPASS and VOYAGER PAD highlight the benefits of combination therapy with low-dose rivaroxaban and aspirin, particularly postrevascularization. Dual antiplatelet therapy is beneficial in select patients, but bleeding risks necessitate individualized treatment approaches. Emerging therapies and procedural advancements offer promising options for high-risk populations, such as those with diabetes, chronic kidney disease, and frailty. This review presents a multidisciplinary approach to PAD management, emphasizing risk stratification and personalized pharmacologic strategies that balance ischemic event prevention with bleeding risk mitigation.