Calcium antagonists for acute ischemic stroke

BACKGROUND: The sudden loss of blood supply in ischemic stroke is associated with increased levels of calcium ions within neurones. Inhibiting this increase could protect neurones and is thought to reduce neurological impairment, disability and handicap after stroke. OBJECTIVES: The aim of this review is to determine whether calcium antagonists reduce the risk of death or dependency after acute ischemic stroke. The influence of different drugs, dosages, routes of administration, time intervals after stroke and trial design on the risk of poor outcome was investigated. SEARCH STRATEGY: Relevant trials were identified in the Specialised Register of Controlled Trials (last searched: March 1999). SELECTION CRITERIA: All truly randomised trials comparing a calcium antagonist with control in patients with acute ischaemic stroke were included. DATA COLLECTION AND ANALYSIS: Two authors assessed all trials and extracted the data. Poor outcome, defined as death or dependency in activities of daily living, was used as the main outcome. Analyses were, if possible, "intention-to-treat". MAIN RESULTS: 46 trials were identified of which 28 were included (7521 patients). No effect of calcium antagonists on poor outcome at the end of follow-up (OR 1.07, 95% CI 0.97/1.18), or on death at end of follow-up (OR 1.10, 95% CI 0.98/1.24) was found. Intravenous administration (i.v.) of calcium antagonists was associated with an increase in the number of patients with poor outcome compared to oral administration (indirect comparisons). Comparisons of different doses of nimodipine suggested that the highest doses were associated with poorer outcome. Administration within 12 hours of onset was associated with an increase in the proportion of patients with poor outcome, but this effect was largely due to the poor results associated with i.v. administration. A subgroup analysis on nimodipine (oral, 120 mg/day) started within 12 hours of stroke onset, did not show a beneficial effect. REVIEWER'S CONCLUSIONS: No evidence is available to justify the use of calcium antagonists in patients with acute ischaemic stroke.