Key result
Clazosentan significantly reduced the risk of angiographic vasospasm (RR 0.58) and vasospasm-related morbidity/mortality (RR 0.80) compared to placebo in patients with aneurysmal subarachnoid hemorrhage, but did not improve functional outcome or mortality.
Why the study?
Does clazosentan reduce the incidence of vasospasm and related complications in patients with aneurysmal subarachnoid hemorrhage?
Meta-Analysis (n=2,156)
Double-blind
Randomized
Yes
Does clazosentan reduce the incidence of vasospasm and related complications in patients with aneurysmal subarachnoid hemorrhage?
Answers are grounded in this paper and cite their sources.
In patients with aneurysmal subarachnoid hemorrhage, clazosentan reduces angiographic vasospasm and vasospasm-related morbidity/mortality but does not improve overall mortality or functional outcomes, while increasing the risk of adverse effects.
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.
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Wang et al. (2012) conducted a meta-analysis in Aneurysmal subarachnoid hemorrhage (aSAH) (n=2,156). Clazosentan vs. Placebo was evaluated on Angiographic vasospasm (RR 0.58, 95% CI 0.48-0.71, p=<0.05). Clazosentan significantly reduced the risk of angiographic vasospasm (RR 0.58) and vasospasm-related morbidity/mortality (RR 0.80) compared to placebo in patients with aneurysmal subarachnoid hemorrhage, but did not improve functional outcome or mortality.
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