Medical Therapy

* **Risk factor modification:** smoking cessation (most critical intervention)[@willigendael2004, @armstrong2014], blood pressure control (target <130/80 mmHg), optimal diabetes management (HbA1c(hemoglobin <7%),A1c [HbA1c] <7%) [@acc2025-b], and lipid management.[@ahaacc2016]
* **Supervised exercise therapy:**therapy (SET):** structured walking programs (3 sessions/week, 30–60 minutes) improve claudication distance by 50–200% and areremain a Class I recommendation (Level[@lane2017, of@conte2025]. EvidenceRecent A)systematic [@lane2017].reviews confirm SET as a primary non-invasive treatment for improving both maximal and pain-free walking distances [@saadi2025].
* **Antiplatelet therapy:** aspirin (75–325 mg daily) or clopidogrel (75 mg daily). The CAPRIE trial demonstrated clopidogrel superiority in the peripheral arterial disease (PAD) subgroup (8.7% relative risk reduction; p=0.0028) [@lancet1996].
* **Statin therapy:** high-intensity therapy (e.g., atorvastatin 40–80 mg) reduces cardiovascular events and limb events (HPS, SPARCL trials).[@hps2002, @amarenco2006] Target LDLlow-density lipoprotein (LDL) <70 mg/dL, or <55 mg/dL in very high-risk patients.
* **Dual-pathway inhibition:** rivaroxaban 2.5 mg BID plus aspirin reduces major adverse cardiovascular events (MACE) and major adverse limb events (MALE) by 24% (COMPASS trial), with increased but manageable bleeding risk [@eikelboom2017].
* **Cilostazol:** phosphodiesterase-3 inhibitor that increases walking distance and improves quality of life;[@thompson2002]life;[@thompson2002, @saadi2025] 100 mg twice daily (not approved in Europe due to concerns about cardiac safety). The 2025 Society for Vascular Surgery (SVS) focused update reaffirms its efficacy for patients with intermittent claudication (IC) [@conte2025].
* **Post-revascularization antithrombotic therapy:** after lower extremity revascularization,revascularization (LER), rivaroxaban 2.5 mg BID plus aspirin reduces acute limb ischemia (ALI) and MACE compared with aspirin alone (VOYAGER-PAD), balancing efficacy against increased bleeding risk in appropriate candidates [@voyager2020]. Recent evidence highlights significant practice variations in antithrombotic selection and the potential role of extended clopidogrel therapy [@wells2025].