What is Cilostazol (Pletal) used for?

Cilostazol (Pletal) Use in Clinical Practice

Cilostazol is primarily indicated for the reduction of symptoms of intermittent claudication in patients with peripheral arterial disease (PAD), as demonstrated by an increased walking distance. In patients with claudication, cilostazol is recommended as first-line pharmacological therapy to improve leg symptoms and increase walking distance 1.

Primary Indications and Mechanism of Action

Cilostazol works as a phosphodiesterase III inhibitor that:

• Increases cyclic adenosine monophosphate (cAMP) in platelets and blood vessels
• Inhibits platelet aggregation
• Produces vasodilation
• Has antiproliferative effects on smooth muscle cells
• Improves lipid profile by increasing HDL cholesterol and decreasing triglycerides 2

Efficacy in Peripheral Arterial Disease

Walking Distance Improvement

• Increases maximal walking distance by 40-60% after 12-24 weeks of therapy 1
• Improves pain-free walking distance significantly compared to placebo 3
• Provides superior efficacy compared to pentoxifylline in comparative trials 1

Quality of Life Benefits

• Significantly improves Peripheral Artery Questionnaire outcomes and physical limitation scores 1
• Enhances quality of life and lower limb functional status 1

Dosing Recommendations

• Standard dose: 100 mg orally twice daily 1
• May be reduced to 50 mg twice daily if adverse effects occur 4
• 100 mg twice daily is more effective than 50 mg twice daily 1

Additional Benefits in PAD Management

• May reduce restenosis after endovascular therapy for femoropopliteal disease 1
• Improves primary patency after bare-metal femoropopliteal stent treatment 1
• Reduces rate of restenosis after stent treatment of femoropopliteal stenosis 1
• Improves target lesion revascularization and reduces major adverse limb events 1

Important Contraindications and Precautions

Absolute Contraindication

• Cilostazol should not be administered to patients with heart failure of any severity 1
  • This contraindication is based on concerns about a class effect, as other phosphodiesterase inhibitors have shown excess mortality in heart failure patients
  • The FDA has mandated a black-box warning regarding this contraindication 1

Drug Interactions

• Significant interactions with CYP3A4 inhibitors (e.g., erythromycin, diltiazem) and CYP2C19 inhibitors (e.g., omeprazole) 5
• Dose reduction may be necessary when coadministered with these inhibitors

Common Adverse Effects

• Headache (most common) 3
• Diarrhea and abnormal stools 5
• Dizziness 2
• Palpitations 1

Clinical Monitoring and Follow-up

• Assess patient tolerance at 2-4 weeks after initiation 1
• Evaluate benefit within 3-6 months to determine long-term therapy benefit 1
• Monitor for cardiovascular symptoms, especially in patients with pre-existing cardiovascular disease

Long-term Safety

The CASTLE study demonstrated no safety signal for cilostazol on all-cause or cardiovascular mortality in long-term use, and serious bleeding events did not appear to be increased, even in patients using antiplatelet agents or anticoagulants 4.

Treatment Algorithm for PAD with Claudication

1. First-line: Supervised exercise program plus risk factor modification
2. Add cilostazol 100 mg twice daily if symptoms persist and patient has no heart failure
3. Consider pentoxifylline as a second-line alternative if cilostazol is not tolerated or contraindicated
4. Consider endovascular or surgical intervention for those with inadequate response to medical therapy and exercise

Cilostazol represents one of the few effective pharmacological options for symptomatic relief of intermittent claudication with demonstrated benefits on walking distance and quality of life.