Calcium antagonists for aneurysmal subarachnoid haemorrhage

Abstract

Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). 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 and have neuroprotective properties. Several types of calcium antagonists have been studied in several clinical trials. To determine whether calcium antagonists improve outcome in patients with aneurysmal SAH. We searched the Cochrane Stroke Group Trials Register (September 2003). In addition, we searched MEDLINE (1966 to October 2003) and EMBASE (1980 to October 2003), handsearched two Russian journals (1990 to 2003) and contacted trialists and pharmaceutical companies (in 1995 and 1996) to identify further studies. All unconfounded, truly randomised controlled trials comparing any calcium antagonist with control. Two reviewers independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information. We analysed 12 trials totalling 2844 patients with SAH (1396 in the treatment group and 1448 in the control group). The drugs analysed were: nimodipine (eight trials, 1574 patients), nicardipine (two trials, 954 patients), AT877 (one trial, 276 patients) and magnesium (one trial, 40 patients). Overall, calcium antagonists reduced the risk of poor outcome: relative risk (RR) 0.82 (95% confidence interval (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 was 20. For oral nimodipine alone the RR was 0.70 (0.58 to 0.84). The RR of death on treatment with calcium antagonists was 0.90 (95% CI 0.76 to 1.07), that of clinical signs of secondary ischaemia 0.67 (95% CI 0.60 to 0.76), and that of CT or MR confirmed infarction 0.80 (95% CI 0.71 to 0.89). Calcium antagonists reduce the risk of poor outcome and secondary ischaemia after aneurysmal SAH. The results for 'poor outcome' depend largely on a single large trial with oral nimodipine; the evidence for nicardipine, AT877 and magnesium is inconclusive. The evidence for nimodipine is not beyond every doubt, but given the potential benefits and modest risks of this treatment, against the background of a devastating natural history, oral nimodipine (60 mg every 4 hours) is currently indicated in patients with aneurysmal SAH. Intravenous administration of calcium antagonists cannot be recommended for routine practice on the basis of the present evidence.