What is the use of Cilostazol (Pletal)?

From the Guidelines

Cilostazol is recommended as an effective therapy to improve symptoms and increase walking distance in patients with lower extremity peripheral artery disease and intermittent claudication, at a standard dosage of 100 mg taken twice daily, in the absence of heart failure, as supported by the most recent guidelines 1.

Key Points

• Cilostazol works by inhibiting phosphodiesterase type 3, preventing platelet aggregation, and causing vasodilation, which improves 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.
• Patients should take cilostazol consistently for at least 12 weeks to evaluate its effectiveness, as symptom improvement may take time.
• A therapeutic trial of cilostazol should be considered in all patients with lifestyle-limiting claudication, in the absence of heart failure, as recommended by the guidelines 1.

Considerations

• Cilostazol should be used cautiously with other antiplatelet medications due to increased bleeding risk.
• Patients should not abruptly discontinue cilostazol and 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.
• Recent data have suggested potential benefit of cilostazol in prevention of in-stent restenosis in patients who have undergone stenting of the femoropopliteal segment, as shown in a blinded RCT 1.

Evidence

• A Cochrane review of 15 double-blind RCTs with 3,718 participants found that cilostazol was associated with improvement in claudication symptoms but no changes in cardiovascular deaths or QOL compared with placebo 1.
• A longitudinal prospective registry found that cilostazol significantly improved Peripheral Artery Questionnaire (PAQ) outcomes and physical limitation score 1.
• A network meta-analysis found that cilostazol improved maximal walking distance and ABI 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 medication used to treat intermittent claudication, a symptom of peripheral arterial disease (PAD) characterized by pain in the legs or buttocks during exercise that subsides with rest 3, 4, 5, 6.
• It works as an antiplatelet agent and vasodilator, improving blood flow and reducing the risk of blood clots 5.

Efficacy of Cilostazol

• Studies have shown that cilostazol improves walking distance in patients with intermittent claudication, with a significant increase in initial and absolute claudication distances compared to placebo 3, 4.
• Cilostazol has also been shown to be more effective than pentoxifylline, another medication used to treat intermittent claudication, in improving walking distance 3, 6.
• However, the evidence for the effectiveness of cilostazol in reducing mortality and cardiovascular events is limited, and more research is needed to fully understand its benefits and risks 3, 4.

Side Effects of Cilostazol

• Common side effects of cilostazol include headache, diarrhea, abnormal stools, dizziness, and palpitations 3, 4, 5.
• These side effects are generally mild and treatable, but may be a concern for some patients 3, 4.

Comparison to Pentoxifylline

• Pentoxifylline is another medication used to treat intermittent claudication, but its effectiveness is less clear, with variable results in studies 7.
• Cilostazol has been shown to be more effective than pentoxifylline in improving walking distance, but the evidence for pentoxifylline's benefits and risks is limited 3, 6, 7.

Quality of Life and Other Outcomes

• There is some evidence that cilostazol may improve quality of life in patients with intermittent claudication, but more research is needed to fully understand its effects on this outcome 3, 4, 5.
• The evidence for cilostazol's effects on other outcomes, such as revascularization, amputation, and cardiovascular events, is limited, and more research is needed to fully understand its benefits and risks 3, 4.