What is the role of cilostazol in treating intermittent claudication?

Cilostazol for Intermittent Claudication

Cilostazol (100 mg orally twice daily) is the first-line pharmacological therapy for patients with peripheral arterial disease (PAD) and intermittent claudication, improving walking distance by 40-60% after 12-24 weeks of therapy and enhancing quality of life. 1, 2

Mechanism and Efficacy

Cilostazol is a phosphodiesterase type 3 inhibitor that:

• Increases cyclic adenosine monophosphate (cAMP)
• Has vasodilator and platelet inhibitory properties
• Modestly increases ankle-brachial index (ABI)
• Improves HDL cholesterol and decreases triglyceride levels 1

Multiple randomized controlled trials demonstrate that cilostazol:

• Increases maximal walking distance by 40-60% after 12-24 weeks
• Improves pain-free walking distance by 59% at the 100 mg twice daily dose 3
• Shows benefits as early as 2-4 weeks after initiation 4
• Provides superior efficacy compared to pentoxifylline 5

Dosing and Administration

• Standard dose: 100 mg orally twice daily
• 100 mg twice daily is more effective than 50 mg twice daily 1
• Should be taken 30 minutes before or 2 hours after meals 6
• Assess tolerance at 2-4 weeks after initiation
• Evaluate benefit within 3-6 months to determine long-term therapy value 2

Absolute Contraindication

• Heart failure of any severity - cilostazol should not be administered to patients with heart failure due to its phosphodiesterase inhibitor properties 1, 2

Drug Interactions

• Significant interactions occur with inhibitors of:
  • CYP3A4 (e.g., erythromycin, diltiazem)
  • CYP2C19 (e.g., omeprazole)
• Dosage reduction should be considered when coadministered with these inhibitors 5
• No clinically significant interactions with aspirin or warfarin 5

Common Side Effects

• Headache (most common)
• Diarrhea or abnormal stools
• Dizziness
• Palpitations 3, 5

Side effects are generally mild to moderate in intensity and often transient or resolve with symptomatic treatment.

Treatment Algorithm for Intermittent Claudication

1. First-line therapy:

   • Supervised exercise program (minimum 30-45 minutes, 3 times weekly for 12 weeks) 1
   • Cilostazol 100 mg twice daily (in patients without heart failure) 1

2. If inadequate response to first-line therapy:

   • Consider pentoxifylline 400 mg three times daily as second-line alternative, though clinical effectiveness is marginal 1
   • Consider endovascular procedures for patients with:
     • Lifestyle-limiting disability despite medical therapy
     • Favorable risk-benefit ratio (e.g., focal aortoiliac occlusive disease) 1

3. Not recommended:

   • Oral vasodilator prostaglandins (beraprost, iloprost)
   • Vitamin E
   • Chelation therapy (potentially harmful) 1

Clinical Pearls

• Cilostazol benefits are seen across various subpopulations including those defined by gender, smoking status, diabetes, duration of PAD, and age 4
• Long-term safety data shows no increased mortality risk with cilostazol use 4
• Cilostazol may reduce restenosis after endovascular therapy for femoropopliteal disease 2
• Unsupervised exercise programs are not well established as effective initial treatment 1

Remember that while symptom improvement is important for quality of life, addressing cardiovascular risk factors remains essential for reducing morbidity and mortality in patients with PAD.