Ketanserin in intermittent claudication: effect on walking distance, blood pressure, and cardiovascular complications

In a 7-center Scandinavian double-blind placebo-controlled study of 179 patients with intermittent claudication, the effect of the serotonin antagonist ketanserin was evaluated on walking distance, brachial and ankle blood pressure, and symptoms. For all centers together, pain-free walking distance was significantly increased after 6 months with both ketanserin (+65%; 71 patients) and placebo (+42%; 78 patients), with no significant difference. However, there was large variability among centers. Classification of "responders" (doubling of walking distance) and patients who deteriorated (decrease of walking distance or dropout for inefficacy) showed significantly more patients responding and significantly fewer patients deteriorating with ketanserin than with placebo. Systemic blood pressure was significantly decreased by ketanserin in hypertensive, but not normotensive, patients, while ankle pressure was unaffected. The incidence and nature of side effects were equal with ketanserin and placebo, but there were more side effects causing dropout in the ketanserin group. An unexpected and possibly important observation was the occurrence of six serious cardiovascular events (myocardial infarction, cerebrovascular complications, and development of rest pain) in the placebo group but none in ketanserin-treated patients. Moreover, there were four additional similar complications in the placebo run-in period. Ketanserin appears to be beneficial in a subgroup of patients with intermittent claudication. A fortuitous finding of this study is that ketanserin might possess a protective effect against thrombovascular complications in patients with intermittent claudication.