What are the indications for Cilostazol (Pletal)?

Indications for Cilostazol

Cilostazol is indicated for the reduction of symptoms of intermittent claudication in patients with peripheral arterial disease (PAD), specifically to improve walking distance and quality of life, provided the patient does not have heart failure of any severity. 1, 2

Primary Indication

• Cilostazol 100 mg orally twice daily is FDA-approved and recommended as first-line pharmacotherapy for all patients with lifestyle-limiting intermittent claudication from PAD 1, 2, 3
• The drug should be offered to patients who have failed or are concurrently receiving supervised exercise therapy 3
• A therapeutic trial of cilostazol should be considered in all patients with lifestyle-limiting claudication who do not have heart failure 2

Clinical Benefits Supporting the Indication

Walking Distance Improvement

• Cilostazol increases maximal walking distance by 40-60% compared with placebo after 12-24 weeks of therapy 2, 4
• The drug improves initial claudication distance by approximately 26.49 meters compared to placebo 5
• Cilostazol increases absolute claudication distance by approximately 39.57 meters compared to placebo 5

Quality of Life Enhancement

• Meta-analyses indicate that cilostazol improves health-related quality of life in addition to walking ability 2
• The drug provides symptom relief that translates into functional improvement for daily activities 3

Hemodynamic Effects

• Cilostazol modestly increases ankle-brachial index (ABI), though this hemodynamic effect does not fully account for the improvement in claudication symptoms 2, 4
• The drug increases ABI by approximately 9% 6

Mechanism Supporting Clinical Use

• Cilostazol is a phosphodiesterase type III inhibitor that increases cyclic adenosine monophosphate (cAMP), providing vasodilator and platelet inhibitory properties 2, 4
• The drug has additional beneficial effects including increasing HDL cholesterol by 10% and decreasing triglycerides by 15% 2, 6
• Cilostazol inhibits vascular smooth muscle cell proliferation and may reduce restenosis after endovascular procedures 2, 4

Absolute Contraindication

Cilostazol is absolutely contraindicated in patients with heart failure of any severity due to FDA black-box warning based on increased mortality risk associated with phosphodiesterase III inhibitors in this population. 2, 4, 7

• Other phosphodiesterase inhibitors (milrinone, vesnarinone) have demonstrated increased mortality in patients with congestive heart failure 2
• Clinicians must screen for any history or symptoms of heart failure before prescribing 7

Dosing and Treatment Duration

• The effective dose is 100 mg orally twice daily, which is superior to 50 mg twice daily 2, 3
• Assess patient tolerance at 2-4 weeks and evaluate benefit within 3-6 months to determine if long-term therapy is beneficial 4
• Approximately 20% of patients discontinue cilostazol within 3 months due to side effects, most commonly headache and diarrhea 4

Comparative Effectiveness

• Cilostazol is significantly more effective than pentoxifylline for improving walking distance in intermittent claudication 8, 4
• Pentoxifylline should only be considered as second-line therapy when cilostazol is contraindicated or not tolerated 3, 2