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.


RESULTS
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
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.
Department of Neurosurgery, Second Military Medical University, Changzheng Hospital, Shanghai, China.
Xiang
X
Wang
Yi-Ming
YM
Li
Wei-Qing
WQ
Li
Cheng-Guang
CG
Huang
Yi-Cheng
YC
Lu
Li-Jun
LJ
Hou
D002545:Brain Ischemia / Q000150:complications; D002423:Cause of Death; D016001:Confidence Intervals; D004146:Dioxanes / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D010919:Placebos; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control
D004146:Dioxanes; D010919:Placebos; D011725:Pyridines; D011743:Pyrimidines; D013449:Sulfonamides; D013777:Tetrazoles; C109641:clazosentan