title: Dissociation of vasospasm-related morbidity and outcomes in patients with aneurysmal subarachnoid hemorrhage treated with clazosentan: a meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  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.
authors: Department of Neurosurgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou Zhejiang Province, People's Republic of China.
authors: Jian
authors: J
authors: Shen
authors: Jian-Wei
authors: JW
authors: Pan
authors: Zuo-Xu
authors: ZX
authors: Fan
authors: Xiao-Xing
authors: XX
authors: Xiong
authors: Ren-Ya
authors: RY
authors: Zhan
mesh_terms: D004146:Dioxanes / Q000627:therapeutic use*; D065130:Endothelin A Receptor Antagonists; D006801:Humans; D009017:Morbidity; D011725:Pyridines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000401:mortality; D013449:Sulfonamides / Q000627:therapeutic use*; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control*
chemical_list: D004146:Dioxanes; D065130:Endothelin A Receptor Antagonists; D011725:Pyridines; D011743:Pyrimidines; D013449:Sulfonamides; D013777:Tetrazoles; C109641:clazosentan