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

Cilostazol Treatment for Intermittent Claudication in Peripheral Artery Disease

Cilostazol 100 mg orally twice daily is the recommended treatment for patients with intermittent claudication due to peripheral artery disease (PAD), as it significantly improves walking distance by 40-60% after 12-24 weeks of therapy. 1

Dosage and Efficacy

• Cilostazol should be administered at 100 mg orally twice daily, which is more effective than the 50 mg twice daily dosage 1
• Treatment results in a 51% geometric mean improvement in maximal walking distance after 24 weeks compared to placebo 2
• Improvements in walking distance are seen as early as 2-4 weeks after starting therapy, with continued increases throughout the 24-week treatment period 3, 4
• Cilostazol improves both pain-free walking distance (by 59%) and maximal walking distance (by 40-60%) 1, 2
• The medication also improves health-related quality of life measures in patients with intermittent claudication 5

Mechanism and Effects

• Cilostazol is a phosphodiesterase type 3 inhibitor that has antiplatelet and vasodilatory effects 1
• It produces a modest increase in ankle-brachial index (ABI), but this hemodynamic effect cannot fully account for the improvement in claudication symptoms 1
• Benefits are observed across various patient subgroups regardless of age, gender, smoking status, diabetes, hypertension, or beta-blocker use 3, 4

Important Contraindications

• Cilostazol is absolutely contraindicated in patients with heart failure of any severity due to its phosphodiesterase inhibitor properties 1
• This contraindication is based on concerns about a potential class effect, as other phosphodiesterase inhibitors have shown excess mortality in heart failure patients 1

Treatment Algorithm

1. First-line therapy: Supervised exercise training (30-45 minutes, at least 3 times weekly for minimum 12 weeks) 1
2. Pharmacologic therapy: Cilostazol 100 mg twice daily for all patients with lifestyle-limiting claudication without heart failure 1
3. Assessment of response:
   • Evaluate tolerance at 2-4 weeks (monitor for headache, diarrhea, dizziness, palpitations) 1
   • Assess clinical benefit at 3-6 months to determine long-term therapy value 1
4. If inadequate response to exercise and cilostazol: Consider endovascular procedures for patients with vocational or lifestyle-limiting disability 1

Alternative Medications

• Pentoxifylline (400 mg three times daily) may be considered as a second-line alternative to cilostazol, but its clinical effectiveness is marginal and not well established 1
• Other proposed therapies such as L-arginine, propionyl-L-carnitine, and ginkgo biloba have limited evidence of effectiveness 1
• Oral vasodilator prostaglandins, vitamin E, and chelation therapy are not recommended for intermittent claudication 1

Safety Profile

• Common adverse effects include headache, diarrhea, abnormal stools, dizziness, and palpitations 2, 6
• Patients taking cilostazol have 2.8 times higher odds of experiencing headache compared to placebo 6
• Long-term safety studies have not shown increased risk of all-cause mortality or cardiovascular events 7, 4
• Approximately 20% of patients discontinue cilostazol within 3 months due to side effects 1

Clinical Pearls and Pitfalls

• Always assess for heart failure before prescribing cilostazol, as it is contraindicated in these patients 1
• The full benefit of cilostazol may take 12-24 weeks to manifest, so encourage patient adherence despite early side effects 1, 4
• Cilostazol may also reduce restenosis after endovascular therapy for femoropopliteal stenosis 1
• Combination therapy with exercise and cilostazol may provide additive benefits for patients with claudication 1