A 62-year-old man with a 40-pack-year smoking history presents with intermittent claudication affecting both lower limbs. Ankle-brachial index is 0.65 bilaterally. He has been counselled on smoking cessation and exercise. Which drug is the first-line pharmacological agent for symptomatic relief in peripheral arterial disease?

Explanation

## First-Line Antiplatelet Agent in Symptomatic PAD **Key Point:** Cilostazol is the preferred first-line drug for symptomatic intermittent claudication in peripheral arterial disease, with proven efficacy in improving walking distance and claudication symptoms. ### Mechanism of Action Cilostazol is a phosphodiesterase-3 (PDE-3) inhibitor that: 1. Increases cAMP in vascular smooth muscle → vasodilation 2. Inhibits platelet aggregation (antiplatelet effect) 3. Improves blood rheology and reduces blood viscosity 4. Has antiproliferative effects on smooth muscle cells ### Clinical Evidence - Increases maximum walking distance by 40–50% in randomized trials - Reduces claudication pain and improves functional capacity - Safe profile with minimal contraindications - Recommended by ACC/AHA guidelines as first-line for symptomatic claudication ### Dosing - Standard dose: 100 mg twice daily (after meals) - Requires 2–4 weeks for symptomatic improvement - Contraindicated in heart failure with reduced ejection fraction (HFrEF) **High-Yield:** Cilostazol is superior to pentoxifylline in clinical trials and is the standard of care in most international guidelines for symptomatic PAD. [cite:Harrison 21e Ch 244] **Clinical Pearl:** Always assess left ventricular function before prescribing cilostazol; it is absolutely contraindicated in HFrEF due to increased mortality risk in heart failure populations.