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Calcium antagonists for aneurysmal subarachnoid haemorrhage
V L Feigin1, G J Rinkel, A Algra
1Department of Neurology, University Hospital Utrecht, PO Box 85500, Utrecht, Netherlands, 3508 GA. g.j.e.rinkel@neuro.azu.nl
Background:
Rupture of an intracranial aneurysm causes bleeding into the subarachnoid space, which may lead to spasm of the cerebral arteries and ischaemic damage to the brain. Prophylactic use of calcium antagonists in patients with ruptured intracranial aneurysms might reduce the risk of ischaemic damage.
Objectives:
This review aimed to determine whether calcium antagonists improve outcome in patients with aneurysmal subarachnoid haemorrhage (SAH).
Search Strategy:
The Cochrane Stroke Group trials register (last searched: March 1999) plus hand searching and personal contacts with trialists and pharmaceutical companies marketing calcium antagonists.
Selection Criteria:
All completed, unconfounded, truly randomised controlled trials comparing any calcium antagonist with control, within ten days of SAH onset. Eleven trials that met the inclusion criteria were included in the overview.
Data Collection And Analysis:
Two reviewers independently extracted data and assessed trial quality. Trialists were contacted to obtain missing information.
Main Results:
We analysed 11 trials totalling 2804 randomized patients with subarachnoid haemorrhage (1376 in the treatment and 1428 in the control group). The drugs analyzed were: nimodipine (eight trials, 1574 patients), nicardipine (two trials, 954 patients), and AT877 (one trial, 276 patients). In 92% of the patients aneurysms were confirmed by angiography or autopsy. Overall, calcium antagonists significantly reduce the risk of poor outcome after subarachnoid haemorrhage: relative risk (RR) 0.82 (95% CI 0. 72-0.93); the absolute risk reduction was 5.1%, the corresponding number of patients needed to treat to prevent a single poor outcome event is 20. For oral nimodipine alone the RR was 0.69 (0.58-0.84). The RR of death on treatment with calcium antagonists was 0.94 (95% CI 0.80-1.10), that of ischaemic neurological deficits 0.67 (95% CI 0.59-0.76), and that of CT-scan documented cerebral infarction 0.80 (95% CI 0.71-0.89).
Reviewer'S Conclusions:
Calcium antagonists reduce the proportion of patients with poor outcome and ischemic neurological deficits after aneurysmal SAH; the risk reduction for case fatality alone is not statistically significant. The results for 'poor outcome' are statistically robust, but depend mainly on trials with oral nimodipine; the evidence for nicardipine and AT877 is inconclusive. The intermediate factors through which nimodipine exerts its beneficial effect after aneurysmal SAH remain uncertain.