Cilostazol: new drug. Intermittent claudication: too little efficacy, too many risks.

(1) Intermittent claudication is usually a sign of generalised vascular atheroma, with prognosis mainly depending on the degree of coronary and cerebral involvement. Treatment is based on smoking cessation and regular exercise. Vasodilators have a purely symptomatic effect, modest at best, in increasing walking distance; (2) Cilostazol, a phosphodiesterase III inhibitor, is licensed in France (after 20 years on the market in Japan) as a treatment intended to increase walking distance in patients with intermittent claudication; (3) A double-blind placebo-controlled trial in 1439 patients showed no reduction in mortality after 3 years of treatment; (4) Cilostazol has been compared with pentoxifylline, another vasodilator with uncertain efficacy, in 3 clinical trials. No tangible difference in efficacy was observed; (5) A meta-analysis of 7 double-blind placebo-controlled trials in a total of 1579 patients showed that cilostazol increased the pain-free walking distance by about 30 metres and the maximum walking distance by about 50 metres; (6) There is some evidence that cilostazol causes a dose-dependent increase in mortality, although the data are not statistically significant. However, excess mortality has been documented with other phosphodiesterase III inhibitors, especially in patients with heart failure; (7) Cilostazol can provoke dose-dependent cardiac arrhythmias, and sometimes haemorrhage (due to its antiplatelet effect); (8) Cilostazol is extensively metabolised by cytochrome P450 isoenzymes CYP 3A4 and CYP 2C6, creating a high risk of pharmacokinetic interactions with other drugs and with food; (9) In practice, patients with intermittent claudication should not be given cilostazol; they should instead be prescribed an antiplatelet drug and encouraged to stop smoking and to exercise regularly.