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.


METHODS
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.


METHODS
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.


RESULTS
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 (approximately 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.
Reilly
M P
MP
Cardiovascular Division, Department of Medicine, School of Medicine, University of Pennsylvania, 432 PHI Bldg., 51 North 39th St., Philadelphia, PA 19104-2699, USA.
Mohler
E R
ER
D000077407:Cilostazol; D002986:Clinical Trials as Topic; D006801:Humans; D007383:Intermittent Claudication / Q000188:drug therapy*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D013777:Tetrazoles / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use
D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D014665:Vasodilator Agents; D000077407:Cilostazol