Abstract / Summary
Background: Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis associated with substantial risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Scope: This comprehensive review examines the epidemiological and pathobiological links between PAD, polyvascular disease, and residual cardiovascular and limb risk. Evidence Synthesis: It summarizes contemporary evidence for integrated management through antithrombotic therapy, intensive lipid lowering, blood pressure and diabetes management, smoking cessation, structured exercise, revascularization when indicated, and longitudinal surveillance. Particular attention is given to dual-pathway inhibition, non-statin lipid-lowering agents, and cardiometabolic therapies, while distinguishing established PAD-specific benefits from subgroup or emerging evidence. Conclusions: A phenotype-based approach integrating ischemic, bleeding, metabolic, functional, and limb-related risk is proposed to support individualized treatment and sustained vascular protection.