Effect of endothelin receptor antagonists on clinically relevant outcomes after experimental subarachnoid hemorrhage: a systematic review and meta-analysis

J Cereb Blood Flow Metab. 2015 Jul;35(7):1085-9. doi: 10.1038/jcbfm.2015.89. Epub 2015 May 6.

Abstract

In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Cerebrovascular Circulation / drug effects
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Endothelin Receptor Antagonists / therapeutic use*
  • Humans
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / pathology
  • Subarachnoid Hemorrhage / physiopathology
  • Treatment Outcome
  • Vasospasm, Intracranial / complications
  • Vasospasm, Intracranial / drug therapy
  • Vasospasm, Intracranial / pathology
  • Vasospasm, Intracranial / physiopathology

Substances

  • Endothelin Receptor Antagonists