What is the recommended treatment and dosage of Cliostazol (cilostazol) for intermittent claudication due to peripheral artery disease (PAD)?

Cilostazol for Intermittent Claudication in Peripheral Artery Disease

Cilostazol 100 mg orally twice daily is the recommended first-line pharmacotherapy for patients with lifestyle-limiting intermittent claudication due to peripheral artery disease, provided they do not have heart failure of any severity. 1, 2

Dosage and Administration

• The standard dose is 100 mg orally twice daily, which is significantly more effective than the 50 mg twice daily dosage 1, 2, 3
• The 100 mg twice daily dose improves maximal walking distance by 40-60% after 12-24 weeks of therapy 1, 2, 4
• Pain-free walking distance improves by approximately 59% with this dosing regimen 1
• Treatment effects are sustained over 24 weeks and continue to increase throughout the treatment period 5

Mechanism and Clinical Effects

• Cilostazol is a phosphodiesterase type 3 inhibitor with antiplatelet and vasodilatory properties 1
• It produces improvements in both initial claudication distance (the distance walked before onset of pain) and absolute claudication distance (maximum walking distance) 6, 7
• The drug modestly increases ankle-brachial index, though this hemodynamic effect does not fully explain the symptomatic improvement 1

Absolute Contraindication

Cilostazol is absolutely contraindicated in patients with heart failure of any severity 1, 2, 3

• The FDA has issued a black box warning prohibiting use in heart failure patients due to increased mortality risk associated with phosphodiesterase III inhibitors 3
• Always screen for heart failure before prescribing cilostazol 1

Treatment Algorithm

• First-line therapy: Supervised exercise training (30-45 minutes, at least 3 times weekly for minimum 12 weeks) 1
• Add cilostazol 100 mg twice daily for all patients with lifestyle-limiting claudication who lack heart failure, either simultaneously with exercise or if exercise alone is inadequate 1, 2
• Second-line alternative: Pentoxifylline 400 mg three times daily may be considered only when cilostazol is contraindicated or not tolerated, though its clinical effectiveness is marginal 1, 2
• Evaluate patient tolerance 2-4 weeks after initiation 3
• Assess clinical benefit within 3-6 months to determine whether to continue long-term therapy 3

Adverse Effects and Tolerability

• Approximately 20% of patients discontinue cilostazol within 3 months due to side effects 1
• Common adverse effects include: headache (most common, with 2.83 times higher odds versus placebo), diarrhea, abnormal stools, palpitations, and dizziness 3, 7
• Serious bleeding events are not increased with cilostazol, even when combined with aspirin, clopidogrel, or anticoagulants 8

Efficacy Across Patient Populations

• Benefits are observed regardless of age, sex, smoking status, diabetes mellitus, duration of PAD, hypertension, prior myocardial infarction, or concurrent beta-blocker use 4, 5
• Combination therapy with supervised exercise and cilostazol may provide additive benefits 1

Safety Profile

• Long-term mortality data show no increased risk of all-cause or cardiovascular mortality with cilostazol 8, 5
• The drug has not been studied in patients with rapidly progressing claudication, leg pain at rest, ischemic leg ulcers, or gangrene 4