Update on calcium antagonists in cerebrovascular diseases

Clinical management of patients affected by subarachnoid hemorrhage has been modified by the use of nimodipine. Although no differences in overall neurologic outcome and rates of symptomatic spasm have been observed between nimodipine and control patients, severity of permanent neurologic deficits consequent to cerebral vasospasm is reduced in the former. On the other hand, clinical trials with nimodipine in ischemic stroke did not substantiate the expected neurologic benefits. A meta-analysis of the two phase IV studies published thus far shows that of 350 patients examined, mortality rate was 11.5% and 19% in subjects given nimodipine and placebo, respectively (n.s.). Cerebral death accounted for 30% of cases in both groups, whereas a lower percentage of cardiac and pulmonary fatal events were observed among nimodipine-treated subjects. Moreover, neurologic outcome of survivors was not significantly different. These results may be associated with the notion that the voltage-operated channel blockade exerted by calcium antagonists is only a part of the complex events leading to the enhancement of calcium ion intracellular concentration as a "common final pathway." However, difficulties encountered in planning clinical trials in acute ischemic stroke also might explain the lack of conclusive results. The feasibility of randomization of an adequate sample of patients and of very early therapeutic intervention after stroke onset are discussed.