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Cilostazol for peripheral arterial disease

  • Review
  • Intervention

Authors


Abstract

Background

Peripheral arterial disease (PAD) affects 4% to 12% of people aged 55 to 70 years and 20% of people over 70 years. The most common complaint is intermittent claudication (IC) characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with IC have a three- to six-fold increase in cardiovascular mortality. Symptoms of IC, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise program. Antiplatelet treatment is beneficial in patients with IC for the reduction of vascular events but has not been shown to influence claudication distance.

Objectives

To determine the effect of cilostazol on improving walking distance and in reducing vascular mortality and cardiovascular events in patients with stable IC.

Search methods

The Cochrane Peripheral Vascular Diseases Group searched their specialised register (last searched August 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2007). We searched MEDLINE (1966 to November 2005), EMBASE (1980 to November 2005), several more specialised databases, and reference lists of articles.

Selection criteria

Double-blind, randomised controlled trials of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable IC or patients undergoing vascular surgical intervention for PAD.

Data collection and analysis

Two authors independently assessed trials for selection and all three authors independently extracted data.

Main results

Seven randomised controlled trials comparing cilostazol with placebo were included.

The weighted mean difference (WMD) for the initial claudication distance (ICD) was improved following treatment with cilostazol 100 mg twice daily (WMD 31.1 m; 95% confidence interval (CI): 21.3 to 40.9 m) and 50 mg twice daily (WMD 41.3 m; 95% CI: -7.1 to 89.7 m) compared with placebo.

Participants receiving cilostazol 150 mg twice daily had an increased ICD (WMD 15.7 m; 95% CI: -9.6 to 41.0 m) compared with those receiving placebo.

One study also included a comparison with pentoxifylline. In this study, participants receiving cilostazol had significant improvement in ICD compared with placebo.

There was no increase in major adverse events including cardiovascular events or mortality in patients receiving cilostazol compared with placebo.

Authors' conclusions

Patients with IC should receive secondary prevention for cardiovascular disease. Cilostazol has been shown to be of benefit in improving walking distance in people with IC. There are no data on whether it results in a reduction of adverse cardiovascular events.

Plain language summary

Cilostazol for peripheral arterial disease

Peripheral arterial disease affects 20% of people over 70 years of age and 4% to 12% of the population aged 55 to 70 years. Approximately 40% of those affected with peripheral arterial disease commonly complain of intermittent claudication. Intermittent claudication is characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Despite the relatively benign prognosis for the affected leg, the symptoms of intermittent claudication are an indicator for the development of systemic atherosclerosis. Compared with age-matched controls, people with intermittent claudication have a three- to six- fold increased chance of dying as a result of cardiovascular events.

The majority of patients with intermittent claudication are treated with best medical management. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, which includes stopping smoking and a structured exercise program. Further cardiovascular risk modification includes treatment for hypertension, diabetes and cholesterol reduction. Antiplatelet treatment is given to reduce the risk of cerebrovascular and coronary events and is effective in the long-term secondary prevention of vascular events in people at high risk of vascular disease, including those who have had ischaemic stroke or acute myocardial infarction. However, antiplatelet therapy has not been shown to influence claudication distance (i.e. the distance walked before the onset of pain). In practice, compliance with best medical treatment is poor and most people continue to have symptoms of intermittent claudication. Until recently there have been three options; supervised exercise, angioplasty or bypass surgery. Compliance with supervised exercise is poor; the long-lasting effect of angioplasty is unproven and surgery carries significant morbidity and mortality. Many pharmacological agents have been advocated for treating intermittent claudication but until recently none have gained acceptance. Cilostazol has recently been approved for the treatment of intermittent claudication. Cilostazol has been shown to be of benefit in improving pain-free walking distance in people with intermittent claudication. There are no data on whether it results in a reduction of cardiovascular events.

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