What is the role of Cilostazol (Pletal) in peripheral arterial disease (PAD)?

From the Guidelines

Cilostazol is recommended to improve leg symptoms and increase walking distance in patients with claudication, with a dose of 100mg twice daily, as supported by the most recent guidelines from the American College of Cardiology and American Heart Association 1. The use of cilostazol in peripheral arterial disease (PAD) has been extensively studied, and the current evidence suggests that it is effective in improving symptoms and increasing walking distance in patients with claudication.

• The 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease recommends cilostazol as a first-line treatment for claudication, with a Class I, Level of Evidence A recommendation 1.
• The guideline also notes that cilostazol may be useful in reducing restenosis after endovascular therapy for femoropopliteal disease, with a Class IIb, Level of Evidence B-R recommendation 1.
• However, cilostazol is contraindicated in patients with congestive heart failure of any severity, due to the potential for increased mortality, with a Class III, Level of Evidence C-LD recommendation 1.
• The side effects of cilostazol, including headache, diarrhea, and palpitations, should be carefully considered and monitored in patients receiving this medication.
• Overall, the current evidence supports the use of cilostazol as a valuable treatment option for patients with claudication, with careful consideration of the potential benefits and risks. Some key points to consider when prescribing cilostazol include:
• Assessing patient tolerance of cilostazol at 2 to 4 weeks and evaluating benefit within 3 to 6 months to determine whether long-term therapy will be beneficial 2.
• Weighing the potential benefits of cilostazol against the potential risks, including adverse effects and cost 2.
• Considering alternative treatment options, such as pentoxifylline or chelation therapy, which are not recommended for treatment of claudication, with a Class III, Level of Evidence B-R recommendation 1.

From the FDA Drug Label

CLINICAL STUDIES: The ability of cilostazol to improve walking distance in patients with stable intermittent claudication was studied in eight large, randomized, placebo-controlled, double-blind trials of 12 to 24 weeks’ duration using dosages of 50 mg b.i.d. (n=303), 100 mg b.i. d. (n=998), and placebo (n=973). The effect of cilostazol on walking distance was seen as early as the first on-therapy observation point of two or four weeks Across the eight clinical trials, the range of improvement in maximal walking distance in patients treated with cilostazol 100 mg b.i.d., expressed as the percent mean change from baseline, was 28% to 100%.

The role of Cilostazol (Pletal) in peripheral arterial disease (PAD) is to improve walking distance in patients with stable intermittent claudication.

• Key benefits include: + Improvement in maximal walking distance + Increase in walking speed + Improvement in walking ability, as assessed by the Walking Impairment Questionnaire
• The medication has been shown to be effective in various subpopulations, including those defined by gender, smoking status, diabetes mellitus, duration of peripheral artery disease, age, and concomitant use of beta blockers or of calcium channel blockers 3.
• The exact mechanism of action is not fully understood, but it is thought to involve the inhibition of phosphodiesterase III (PDE III), leading to inhibition of platelet aggregation and vasodilation 4.

From the Research

Role of Cilostazol in Peripheral Arterial Disease (PAD)

• Cilostazol, a phosphodiesterase III inhibitor, is indicated to treat the symptoms of intermittent claudication and increase walking distance in patients with peripheral arterial disease (PAD) 5.
• The medication has been shown to improve initial and absolute claudication distances, with a significant increase in walking distances compared to placebo 6, 7, 8, 9.
• Cilostazol has also been found to improve quality of life in patients with intermittent claudication, with significant improvements in physical component subscale and composite physical component score 7, 9.

Efficacy and Safety

• The efficacy of cilostazol has been demonstrated in several randomized, double-blind, placebo-controlled trials, with significant improvements in walking distances and quality of life compared to placebo 6, 7, 8, 9.
• Cilostazol has been found to be generally well tolerated, with common adverse events including headache, diarrhea, abnormal stools, and dizziness 5, 6, 7, 8, 9.
• There is no clear evidence of a difference between cilostazol and placebo in terms of all-cause mortality or cardiovascular events, although larger, adequately powered studies are needed to assess this relationship 5, 6, 8.

Subgroup Analysis

• Cilostazol has been found to be effective in improving walking distances in various subgroups, including patients with different ages, sexes, smoking statuses, and comorbidities 8.
• The medication has also been found to be effective in patients with different durations of PAD, diabetes, hypertension, and prior myocardial infarction 8.

Comparison with Other Treatments

• Cilostazol has been compared to pentoxifylline, with cilostazol found to be significantly more effective in improving walking distances and quality of life 6, 7.
• The medication has also been found to be more effective than placebo in improving walking distances, with a significant increase in absolute claudication distance compared to placebo 9.