Flunarizine in stroke treatment (FIST): a double-blind, placebo-controlled trial in Scandinavia and the Netherlands

Abstract

Introduction ‐ An international, multicenter trial was conducted in 331 patients to determine the effect of a large dose of flunarizine (a calcium entry blocker) in the treatment of acute ischemic stroke in the territory of the Middle cerebral artery. Methods ‐ The administration of the trial medication should start within 24 h after the initial symptoms of stroke. According to a random schedule, the patients were assigned to a 4‐weeks double‐blind treatment with either flunarizine (n= 166) or placebo (n= 165): one week intravenous administration (50 mg daily), followed by 3 weeks oral treatment (week 2, 21 mg daily; week 3–4, 7 mg daily). All patients had to be investigated by computerized tomography (CT) within 7 days after stroke onset; 36 patients were secundarily excluded because the CT showed another pathology. During the treatment period, other “stroke therapies” were not allowed. Patients were followed up for 24 weeks. Results ‐ After the 24 weeks trial period, the percentage of patients who were dead or pendent (modified Rankin score 3–5) was similar in both treatment groups (flunarizine 67%, placebo 65%). During the trial, the scores for handicap severity (modified Rankin scale), neurological status (Orgogozo) and activities of daily living (modified Barthel index) strongly improved in both treatment groups, but no differences were found between the treatment groups. In this trial, the administration of trial treatment started relatively late after stroke onset (flunarizine group: mean time interval 13.5 h; placebo 12.3 h). A subgroup of patients received trial medication within 6 h after stroke onset (flunarizine n= 31; placebo n= 29). Also in this subgroup, no differences were found between the flunarizine and placebo group. Conclusion ‐ Flunarizine did not improve neurologic and functional outcome in patients with acute ischemic stroke.

Ipsilesional Bias and Processing Speed are Important Predictors of Functional Dependency in the Neglect Phenomenon After a Right Hemisphere Stroke

“…The modified Rankin Scale has also been used as a dichotomized measure of "poor" and "good" outcomes after stroke. A common procedure when dichotomizing the mRS is based on the patients' need for assistance in performing daily activities (e.g., Diener, 1998;Franke et al, 1996). The design of the mRS indicates a clinically relevant difference between the mRS scores of 2 (= no need of assistance in performing daily activities) and 3 (= some need of assistance).…”

Neuroprotection for ischemic stroke: Past, present and future

“…There was no effect of treatment (Franke et al, 1996). Pentoxifylline, a vasodilator with possible rheologic effects, was studied in a phase II study of 297 subjects with acute stroke randomized to treatment within 12 hours.…”

Guidelines for the Early Management of Patients With Acute Ischemic Stroke

“…430 Trials of flunarizine, isradipine, and darodipine were also negative. [733][734][735] Although nicardipine is used to treat elevated blood pressure in the setting of stroke, the agent has had limited testing for neuroprotective treatment of the stroke itself. 736,737 A meta-analysis published in 2000 of the calcium channel-blocking agents found no evidence that this class of drug is effective in improving outcomes after ischemic stroke.…”