Calcium antagonists for aneurysmal subarachnoid haemorrhage.
BACKGROUND
Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage. Its pathogenesis has not been elucidated yet, but may be related to vasospasm. Experimental studies have indicated that calcium antagonists can prevent or reverse vasospasm. Calcium antagonists have been studied in several trials, but data are conflicting. There is no overview concerning all available calcium antagonists.


OBJECTIVE
To determine whether calcium antagonists improve outcome in patients with aneurysmal subarachnoid haemorrhage (SAH).


METHODS
We searched the Cochrane Stroke Group Trials Register (last searched November 2001). In addition, we handsearched two Russian journals (1990-1995) and contacted trialists and pharmaceutical companies to identify further studies


METHODS
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.


METHODS
Two reviewers independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information


RESULTS
We analysed 11 trials totaling 2804 randomised patients with subarachnoid haemorrhage (1376 in the treatment and 1428 in the control group). The drugs analysed 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 reduced the risk of poor outcome after subarachnoid haemorrhage: relative risk (RR) 0.82 (95% CI 0.72 to 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 to 0.84). The RR of death on treatment with calcium antagonists was 0.94 (95% CI 0.80 to 1.10), that of ischaemic neurological deficits 0.67 (95% CI 0.59 to 0.76), and that of CT-scan documented cerebral infarction 0.80 (95% CI 0.71 to 0.89).


CONCLUSIONS
Calcium antagonists reduce the proportion of patients with poor outcome and ischaemic neurological deficits after aneurysmal SAH. The results for 'poor outcome' are statistically robust, but depend largely on one large trial with oral nimodipine; the evidence for nicardipine and AT877 is inconclusive. The evidence for nimodipine is not beyond every doubt, but given the potential benefits and modest risks associated with this treatment, against the background of a devastating natural history, oral nimodipine (60 mg every 4 hours) is indicated in patients with aneurysmal SAH. Intravenous administration of calcium antagonists cannot be recommended on the basis of the present evidence. For oral nimodipine uncertainty remains regarding the (dis)advantages in patients in poor clinical condition on admission or in patients with established cerebral ischaemia, the optimal dose and time window, the question whether other types of calcium antagonists offer better protection and the intermediate factors through which nimodipine exerts its beneficial effect after aneurysmal SAH.
Rinkel
G J
GJ
Department of Neurology, University Hospital Utrecht, PO Box 85500, Utrecht, Netherlands, 3508 GA. g.j.e.rinkel@neuro.azu.nl
Feigin
V L
VL
Algra
A
A
Vermeulen
M
M
van Gijn
J
J
D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy*; D016896:Treatment Outcome
D002121:Calcium Channel Blockers