Cilostazol: Treatment of Intermittent Claudication

OBJECTIVE: To review the pharmacology and clinical utility of cilostazol, an antiplatelet and vasodilator agent approved for the management of intermittent claudication. DATA SOURCES: Primary literature on cilostazol was identified from a comprehensive MEDLINE literature search (1980–February 2000). Selected meeting abstracts and manufacturer literature were also used as source material. Indexing terms included cilostazol, intermittent claudication, platelet inhibitors, and restenosis. STUDY SELECTION: Human clinical, pharmacokinetic and randomized comparative trials performed in the US and Asia were reviewed. Selected in vitro, ex vivo, and animal studies were evaluated when human data were not available. DATA SYNTHESIS: Intermittent claudication, defined as reproducible discomfort of a muscle group induced by exercise and relieved by rest, is the most common clinical manifestation of peripheral arterial disease (PAD). Cilostazol, a specific inhibitor of cyclic adenosine monophosphate phosphodiesterase in platelets and vascular smooth-muscle cells, is a potent antiplatelet agent and vasodilator that reduces vascular proliferation and has lipid-lowering effects in vivo. Recent multicenter, randomized, placebo-controlled trials have led to approval of cilostazol by the Food and Drug Administration for relief of intermittent claudication in patients with stable PAD. Cilostazol doubled walking distances and improved quality of life compared with placebo in these studies. One trial found that cilostazol was more effective than pentoxifylline, the only alternative pharmacologic therapy for claudication. Although frequent (∼50%) minor adverse effects, including headache, diarrhea, and palpitations, may occur in clinical practice, cilostazol has not been associated with major adverse events or increased mortality. Small, nonblind studies suggest that cilostazol may prove useful in preventing thrombosis and restenosis following percutaneous coronary interventions, although these remain unlabeled uses. CONCLUSIONS: The unique combination of antiplatelet, vasodilatory, and antiproliferative effects of cilostazol appear to make it an attractive agent for use in patients with PAD. Clinical trials demonstrating a significant improvement in walking distances with cilostazol therapy suggest that it will be an important tool in improving symptoms and quality of life in patients with intermittent claudication.