What is the use of Cilostazol (Pletal)?

From the Guidelines

Cilostazol is recommended as a first-line treatment for intermittent claudication in patients with lower extremity peripheral artery disease, with a standard dosage of 100 mg taken twice daily, as it has been shown to improve symptoms and increase walking distance, as evidenced by a Cochrane review of 15 double-blind RCTs with 3,718 participants 1.

Key Considerations

• Cilostazol works by inhibiting phosphodiesterase type 3, which prevents platelet aggregation and causes vasodilation, improving blood flow to the legs.
• Common side effects include headache, diarrhea, and dizziness.
• Cilostazol is contraindicated in patients with heart failure, as it can worsen this condition, as noted in the package insert and supported by studies of other phosphodiesterase inhibitors 1.
• Patients should take cilostazol consistently for at least 12 weeks to evaluate its effectiveness, as symptom improvement may take time.
• Cilostazol should be used cautiously with other antiplatelet medications due to increased bleeding risk, and patients should inform healthcare providers about all medications they're taking to avoid potential interactions, particularly with strong CYP3A4 and CYP2C19 inhibitors which can increase cilostazol blood levels.

Benefits and Risks

• Benefits: improvement in claudication symptoms, increase in walking distance, and potential benefit in prevention of in-stent restenosis in patients who have undergone stenting of the femoropopliteal segment 1.
• Risks: headache, diarrhea, dizziness, palpitations, and potential increased risk of bleeding when used with other antiplatelet medications.

Monitoring and Follow-up

• Patients should be monitored for side effects and efficacy, with assessment of walking distance and claudication symptoms at regular intervals.
• Cilostazol therapy should be reassessed at 3 to 6 months to determine whether long-term therapy will be beneficial, as suggested by a longitudinal prospective registry 1.

From the FDA Drug Label

INDICATIONS AND USAGE Cilostazol tablets are indicated for the reduction of symptoms of intermittent claudication, as indicated by an increased walking distance.

CLINICAL PHARMACOLOGY Mechanism of Action: The mechanism of the effects of cilostazol on the symptoms of intermittent claudication is not fully understood Cilostazol and several of its metabolites are cyclic AMP (cAMP) phosphodiesterase III inhibitors (PDE III inhibitors), inhibiting phosphodiesterase activity and suppressing cAMP degradation with a resultant increase in cAMP in platelet and blood vessels, leading to inhibition of platelet aggregation and vasodilation, respectively

• Main Use: Cilostazol is used for the reduction of symptoms of intermittent claudication.
• Key Mechanism: It works by inhibiting phosphodiesterase III (PDE III), leading to inhibition of platelet aggregation and vasodilation.
• The exact mechanism of how cilostazol reduces symptoms of intermittent claudication is not fully understood 2 2.

From the Research

Cilostazol Overview

• Cilostazol is a selective inhibitor of phosphodiesterase-III with antiplatelet, antithrombotic, and vasodilating properties 3.
• It exhibits antiproliferative effects on smooth muscle cells and has beneficial effects on high-density lipoprotein-cholesterol and triglyceride levels 3.

Efficacy in Intermittent Claudication

• Cilostazol has been shown to increase walking distances and improve quality of life in patients with moderate to severe intermittent claudication 3, 4, 5.
• Randomized, double-blind, placebo-controlled trials have demonstrated that cilostazol significantly increases maximal walking distance and pain-free walking distance compared to placebo 3, 4.
• Cilostazol has also been compared to pentoxifylline, with results showing that cilostazol is more effective in increasing walking distances 3, 5.

Safety and Tolerability

• Cilostazol is generally well tolerated, with common adverse events including headache, diarrhea, abnormal stools, infection, rhinitis, and peripheral edema 3, 4.
• Significant drug interactions are observed when cilostazol is coadministered with other agents that inhibit cytochrome P450 (CYP) 3A4 or CYP2C19 3.
• Cilostazol is contraindicated in patients with congestive heart failure and severe hepatic or renal impairment 3, 6.

Comparison to Other Treatments

• Cilostazol has been compared to other treatments for intermittent claudication, including pentoxifylline, naftidrofuryl, and buflomedil 7, 6.
• The choice of cilostazol as a treatment option should be based on individual patient needs and medical history, as well as consideration of the potential benefits and risks 3, 6.