Flunarizine in ischemic stroke; A randomised, multicentre, placebo- controlled, double blind study

In five neurological or internal medical centres, 422 patients aged between 50 and 85 years were randomly allocated to a treatment with either intravenous flunarizine or placebo in addition to a standard medication (haemodilution with hydroxyaethyl-starch, aspirin, low dose heparine) following their first supratentorial ischaemic stroke. The therapy started within 36 hours of the occurrence. Flunarizine was given intravenously at a dose of 25 mg b. i. d. for seven days, then orally, 10 mg in the morning and 20 mg in the evening, for the following three weeks. During the four-week observation period 20 patients died in the placebo and 25 in the flunarizine treated group. The neurological status was quantitatively evaluated on the day of admission (day 0) and on days 1, 4, 7, 14, 21, and 28 using a slightly modified Mathew scale. There were no statistically significant differences between the treated and the placebo groups with regard to sex, age and preexisting risk factors. The study medication was well tolerated, a higher proportion of weariness and thrombophlebitis at the site of the intravenous infusion being the only relevant side effects of flunarizine. Importantly, there was no alteration of heart rate or blood pressure. Testing the homogeneity of the five centres involved in the study by comparing the results in the placebo groups we found the data of centre 2 significantly deviating from all other centres: the data in the Mathew scale subscore sensomotor functions was significantly better in centre 2 than in the honogeneous centres 1, 3, 4, and 5. Several factors were identified in centre 2 which probably caused this lack of homogeneity in the placebo results. Therefore, further analysis of the effects of treatment was carried out in the homogeneous centres. In these the improvement of the sensomotor functions was significantly greater in the flunarizine treated patients than in the placebo group. The patients were furthermore categorised in different groups, pathogenetically defined by their type of individual angiopathy as revealed by computed cerebral tomography (CT). Those treated with flunarizine showed a significant improvement (p = 0.01) when compared to those given placebo in the group of patients with a clear CT lesion (lacunar infarction, territorial infarction, haemodynamic infarction or a combination of these). These data indicates that flunarizine given within 36 hours after an ischaemic cerebral stroke is effective. The subscores for mental functions and activities in daily life showed no significant differences between the flunarizine treated and the placebo groups. This may be owing to the fact that these variables mainly depend on functions of the non-injured hemispere.