Nimodipine in acute ischemic stroke: a double-blind controlled study

Abstract

Nimodipine (BAY e 9736), a new dihydropyridine derivative, has been shown to reduce neurological deficits and mortality induced by acute cerebral ischemia in experimental studies. We investigated the effects of this calcium antagonist in patients with acute ischemic stroke through a randomized, double-blind, parallel-designed trial in which nimodipine was compared with placebo. Forty-one of 54 screened cases were found to fulfil the inclusion criteria (sudden occurrence of a focal neurological deficit secondary to an acute ischemic event in the carotid area diagnosed after a complete neurological work-up) and entered the study. Nineteen of them were treated with nimodipine (40 mg t.i.d. administered for 28 days) and the remaining 22 with placebo, given in identical tablets. In all patients the treatment started within 12 h after the onset of the symptoms. Course and intensity of the neurological deficit were evaluated by the Mathew Scale (slightly modified). Forty patients concluded the trial. Nimodipine was withdrawn in one case following the occurrence of a skin rash whose causative relation with the test drug could not be clarified. Altogether, however, nimodipine was well tolerated and no severe cardiovascular adverse reactions were observed. In terms of efficacy, the scores obtained by the Mathew Scale showed a higher rate of improvement on nimodipine than on placebo, thus indicating that patients receiving the latter drug did not fare as well as those receiving the test medication. Our data suggest that nimodipine may be beneficial in the treatment of acute stroke.

Nimodipine in Animal Model Experiments of Focal Cerebral Ischemia

“…However, repeat analysis of data on the functional outcome of patients in this trial, by dichotomizing the score on the disability item in the modified Mathew scale, shows a difference that was not statistically significant. 7 The supposedly positive results of this first randomized controlled trial were followed by a small trial, 51 which showed similar results. In the introduction to that article, the authors refer to an animal experiment by Germano et al 52 Subsequent reports on larger clinical trials 3,4,53,54 refer in the introduction to a single positive animal experiment, to the proven effectiveness of nimodipine in the treatment of subarachnoid hemorrhage, and primarily to the positive results of the first randomized controlled trial with nimodipine in ischemic stroke.…”

Effect of Intravenous Nimodipine on Blood Pressure and Outcome After Acute Stroke

“…14 The authors found a correlation between nimodipine-induced reduction in BP and unfavorable outcome. The trial design of INWEST was based on the early positive results of oral nimodipine in acute ischemic stroke 15,16 and a positron emission tomography study 17 of intravenously administered nimodipine, which indicated a statistically significant beneficial effect on long-term recovery in patients with acute ischemic stroke. Like other calcium channel blockers, nimodipine has an antihypertensive property, and one of its main mechanisms of action is vasodilatation, causing decreased peripheral vascular resistance.…”

Clinical trials for cytoprotection in stroke

“…28 Forty-six patients with ischemic carotid artery territory stroke [National Institute of Health Stroke Scale (NIHSS) score [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] were enrolled within 24 h of symptom onset. In part A, patients were randomized 3:1 to a single bolus of Cerestat or placebo.…”