An Update on Efficacy and Safety Profile of Clazosentan in Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.

AIMS: The present meta-analysis was conducted to provide an update on the efficacy and safety profile of clazosentan with different doses in aSAH.

METHODS: We performed a comprehensive and electronic search of the following databases updated to September, 2018: the Cochrane library, Embase and PubMed, to identify relevant clinical trials. Trials of the effectiveness of clazosentan in treating cerebral vasospasm after aSAH were studied, of which the main outcomes included new cerebral infarction (NCI), delayed ischemic neurological deficit (DIND), vasospasm associated with morbidity/mortality (M/M), angiographic vasospasm, rescue therapy and adverse events. We applied the Revman 5.3 software for this meta-analysis to analyze the combined pooled ORs with its 95% confidence interval using a fixed- or random-effects model on the basis of heterogeneity.

RESULTS: Totally, 5 randomized placebo-controlled trials (RCTs) were included in this meta-analysis. Beneficial outcome was found in patients who received higher dose of clazosentan (＞5mg/h) after aSAH based on decreased incidence of DINDs (OR=1.76, 95%CI=1.16-2.69, P=0.008), NCI (OR=2.31, 95%CI=1.34-3.95, P=0.002) and angiographic vasospasm (OR=1.85,95%CI=1.19-2.89, P=0.007). Meanwhile, other parameters such as vasospasm-related morbidity/mortality, rescue therapy and adverse events showed no statistical significance (P＞0.05) between high and low doses of clazosentan.

CONCLUSION: The significant beneficial outcomes of high-dose clazosentan have been proved in preventing cerebral vasospasm and subsequent cerebral infarction compared with low-dose clazosentan, with a manageable safety profile. However, high doses of clazosentan had no significant effect on rescue therapy and vasospasm- related morbidity/mortality.