Effect of Clazosentan in Patients with Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials

BACKGROUND Cerebral vasospasm is the most important potentially treatable cause of mortality and morbidity following aneurysmal subarachnoid hemorrhage (aSAH). Clazosentan, a selective endothelinreceptor antagonist, has been suggested to help reduce the incidence of vasospasm in patients with aSAH. However, the results were controversial in previous trials. This meta-analysis attempts to assess the effect of clazosentan in patients with aSAH. METHODOLOGY/PRINCIPAL FINDINGS We systematically searched Pubmed, Embase, and the Cochrane Library from their inception until June, 2012. All randomized controlled trials (RCTs) related to the effect of clazosentan in aSAH were included. The primary outcomes included the incidence of angiographic vasospasm, new cerebral infarction (NCI), delayed ischemic neurological deficits (DIND), and vasospasm-related morbidity/mortality (M/M); the second outcomes included the occurrence of rescue therapy, all-cause-mortality, and poor outcome. 4 RCTs were included with a total of 2156 patients. The risk of angiographic vasospasm (relative risk [RR] =0.58; 95% CI, 0.48 to 0.71), DIND (RR=0.76; 95% CI, 0.62 to 0.92), and vasospasm-related M/M (RR=0.80; 95% CI, 0.67 to 0.96) were statistically significantly reduced in the clazosentan group. Patients treated with clazosentan had a reduced occurrence of rescue therapy (RR=0.62; 95% CI, 0.49 to 0.79). However, no statistically significant effects were observed in NCI (RR=0.74; 95% CI, 0.52 to 1.04), mortality (RR=1.03; 95% CI, 0.71 to 1.49), and poor outcome (RR=1.12; 95% CI, 0.96 to 1.30). CONCLUSIONS/SIGNIFICANCE Our pooling data supports that clazosentan is probably effective in preventing the occurrence of angiographic vasospasm, vasospasm-related DIND, vasospasm related M/M, and rescue therapy. However, no evidence lends significant supports to the benefits of clazosentan in decreasing the occurrence of NCI, mortality or improving the functional outcome.