Dissociation of vasospasm-related morbidity and outcomes in patients with aneurysmal subarachnoid hemorrhage treated with clazosentan: a meta-analysis of randomized controlled trials

A review

Jian Shen M.D. 1 , Jian-Wei Pan M.D., Ph.D. 1 , Zuo-Xu Fan M.D. 1 , Xiao-Xing Xiong M.D. 2 and Ren-Ya Zhan M.D., Ph.D. 1
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  • 1 Departments of Neurosurgery and
  • 2 Anesthesiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou Zhejiang Province, People's Republic of China
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Object

Clazosentan therapy after aneurysmal subarachnoid hemorrhage (SAH) has been found to be effective in reducing the incidence of vasospasm in randomized controlled trials. However, while vasospasm-related morbidity, including delayed ischemic neurological deficits (DINDs) and delayed cerebral infarctions, was consistently decreased, statistical significance was not demonstrated and outcomes were not affected by clazosentan treatment. The objective of this meta-analysis was to determine whether clazosentan treatment after aneurysmal SAH significantly reduced the incidence of DINDs and delayed cerebral infarctions and improved outcomes.

Methods

All randomized controlled trials investigating the effect of clazosentan were retrieved via searches with sensitive and specific terms. Six variables were abstracted after the assessment of the methodological quality of the trials. Analyses were performed following the method guidelines of the Cochrane Back Review Group.

Results

Four randomized, placebo-controlled trials met eligibility criteria, enrolling a total of 2181 patients. The meta-analysis demonstrated a significant decrease in the incidence of DINDs (relative risk [RR] 0.76 [95% CI 0.62–0.92]) and delayed cerebral infarction (RR 0.79 [95% CI 0.63–1.00]) in patients treated with clazosentan after aneurysmal SAH. However, this treatment regimen was not shown to outcomes including functional outcomes measured by Glasgow Outcome Scale-Extended (RR 1.12 [95% CI 0.96–1.30]) or mortality (RR 1.02 [95%CI 0.70–1.49]). Adverse events, including pulmonary complications, anemia, and hypotension, were all significantly increased in patients who received clazosentan therapy.

Conclusions

The results of the present meta-analysis show that treatment with clazosentan after aneurysmal SAH significantly reduced the incidence of the vasospasm-related DINDs and delayed cerebral infarctions, but did not improve poor neurological outcomes in patients with aneurysmal SAH. Further study is required to elucidate the dissociation between vasospasm-related morbidity and outcomes.

Abbreviations used in this paper:CONSCIOUS = Clazosentan in Aneurysmal Subarachnoid Hemorrhage; DIND = delayed ischemic neurological deficit; GOSE = Glasgow Coma Scale–Extended; RCT = randomized controlled trial; RR = relative risk; SAH = subarachnoid hemorrhage; WFNS = World Federation of Neurosurgical Societies.

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Contributor Notes

Address correspondence to: Ren-Ya Zhan, M.D., Department of Neurosurgery, First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou City, 310003 Zhejiang Province, People's Republic of China. email: sjzju@163.com.

Please include this information when citing this paper: published online May 3, 2013; DOI: 10.3171/2013.3.JNS121436.

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