Tirilazad for aneurysmal subarachnoid haemorrhage.
BACKGROUND
Delayed cerebral ischaemia is a significant contributor to poor outcome (death or disability) in patients with aneurysmal subarachnoid haemorrhage (SAH). Tirilazad is considered to have neuroprotective properties in animal models of acute cerebral ischaemia.


OBJECTIVE
To assess the efficacy and safety of tirilazad in patients with aneurysmal SAH.


METHODS
We searched the Cochrane Stroke Group Trials Register (last searched October 2009); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2009); MEDLINE (1966 to October 2009); EMBASE (1980 to October 2009); and the Stroke Trials Directory, the National Center for Complementary and Alternative Medicine, and the National Institute of Health Clinical Trials Database (searched October 2009). We handsearched 10 Chinese journals, searched the reference lists of relevant publications, and contacted the manufacturers of tirilazad.


METHODS
Randomised trials of tirilazad started within four days of SAH onset, compared with placebo or open control in patients with aneurysmal SAH documented by angiography and computerised tomography (CT) scan or cerebrospinal fluid examination, or both.


METHODS
We extracted data relating to case fatality, poor outcome (death, vegetative state, or severe disability), delayed cerebral ischaemia (or symptomatic vasospasm), cerebral infarction and adverse events of treatments. We pooled the data using the Peto fixed-effect method for dichotomous data.


RESULTS
We included five double-blind, placebo-controlled trials involving 3821 patients; there was no significant heterogeneity. Oral or intravenous nimodipine was used routinely as a background treatment in both groups in all trials. There was no significant difference between the two groups at the end of follow up for the primary outcome, death (odds ratio (OR) 0.89, 95% confidence interval (CI) 0.74 to 1.06), or in poor outcome (death, vegetative state or severe disability) (OR 1.04, 95% CI 0.90 to 1.21). During the treatment period, fewer patients developed delayed cerebral ischaemia in the tirilazad group than in the control group (OR 0.80, 95% CI 0.69 to 0.93). Subgroup analyses did not demonstrate any significant difference in effects of tirilazad on clinical outcomes. Leukocytosis and prolongation of Q-T interval occurred significantly more frequently in the treatment group in only one trial evaluating tirilazad at high dose. There was no significant difference in infusion site disorders or other laboratory parameters between the two groups.


CONCLUSIONS
There is no evidence that tirilazad, in addition to nimodipine, reduces mortality or improves poor outcome in patients with aneurysmal SAH.
Zhang
Shihong
S
Department of Neurology, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan Province, China, 610041.
Wang
Lichun
L
Liu
Ming
M
Wu
Bo
B
D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009553:Nimodipine / Q000627:therapeutic use; D011281:Pregnatrienes / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D011281:Pregnatrienes; D009553:Nimodipine; C053355:tirilazad