Calcium antagonists for ischemic stroke: a systematic review.

BACKGROUND AND PURPOSE Stroke is a common disease, and many trials with calcium antagonists as possible neuroprotective agents have been conducted. The aim of this review is to determine whether calcium antagonists reduce the risk of death or dependency after acute ischemic stroke. METHODS Acute stroke trials were identified with help of the Cochrane Collaboration Stroke Group and personal contacts. All randomized trials (published and unpublished) investigating a calcium antagonist (acting on voltage-sensitive calcium channels) were included. Poor outcome, defined as death or dependency in activities of daily living, was used as main outcome. Analyses were, if possible, "intention-to-treat"; pooled relative risks with 95% CIs were calculated. RESULTS Forty-seven trials were identified, of which 29 were included (7665 patients). No effect of calcium antagonists on poor outcome at the end of follow-up (relative risk, 1.04; 95% CI, 0.98 to 1.09) or on death at end of follow-up (relative risk, 1.07; 95% CI, 0.98 to 1.17) was found. Sensitivity analyses on route of administration and time interval between stroke and start of treatment showed no effect on outcome. In subgroups of unpublished and methodologically sound trials, a statistically significant negative effect for calcium antagonists was found. This contrasts with results of published trials and trials of moderate or poor methodological quality. CONCLUSIONS The presented evidence rules out a clinically important effect of calcium antagonists after ischemic stroke. The large amount of data leads to narrow CIs with no significant heterogeneity, and the overall results are therefore likely to be statistically robust.