Polyvascular Atherosclerotic Disease Across Contemporary ESC Guidelines: Key Updates, Clinical Gaps, and Future Perspectives

Atherosclerosis is a systemic disorder, yet patients with coronary, cerebrovascular, and lower-extremity peripheral artery disease (PAD) are commonly managed through separate territory-specific pathways. Polyvascular atherosclerotic disease, defined as the coexistence of clinically relevant obstructive atherosclerosis in at least two major arterial territories, is associated with a stepwise increase in cardiovascular and limb events. This narrative review critically integrates the 2024 European Society of Cardiology (ESC) guidelines for peripheral arterial and aortic diseases and chronic coronary syndromes with the 2023 ESC guideline for acute coronary syndromes, focusing on cross-territory detection, risk stratification, antithrombotic therapy, lipid lowering, management of residual risk, and follow-up. The guidelines are broadly concordant in recognizing polyvascular involvement as a marker of high ischemic risk and in recommending intensive secondary prevention. Current evidence supports symptom-driven and targeted evaluation of additional arterial territories when findings may alter treatment or procedural planning; routine multisite imaging has not been shown to improve clinical outcomes. Antithrombotic therapy should be determined by clinical phase and bleeding risk rather than territory count alone: single antiplatelet therapy remains the chronic baseline, dual antiplatelet therapy is used after acute coronary syndrome or percutaneous coronary intervention, and aspirin plus vascular-dose rivaroxaban may be considered in selected stable high-risk patients without high bleeding risk. An LDL-cholesterol concentration below 55 mg/dL with a reduction of at least 50% from baseline, together with blood-pressure and diabetes management, smoking cessation, exercise, and rehabilitation, remains central across all phenotypes. Important gaps include inconsistent definitions, limited outcome-based screening evidence, absence of direct comparisons between extended antithrombotic strategies, and underrepresentation of frail, renally impaired, and high-bleeding-risk patients. An integrated approach combining total atherosclerotic burden, clinical activity, ischemic risk, bleeding risk, and the actionability of additional testing may improve care beyond isolated territory-specific algorithms.