Cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhages (aSAH) causes significant cause of morbidity and mortality. Clazosentan is an endothelin receptor antagonist that inhibits endothelin-mediated vasoconstriction, and is being tested clinically for preventing vasospasm. A meta-analysis by Shen et al (J. Neurosurgery, July 2013) of 4 randomized placebo-controlled trials enrolling 2181 patients examines clazosentan’s effect on vasospasm-related morbidity and mortality, and drug-related adverse events in aSAH. These 4 randomized trials showed substantial variation in results. However, the meta-analysis showed that clazosentan treatment after aSAH significantly reduced the incidence of vasospasm-related neurological deficits and delayed cerebral infarctions, but failed to improve poor neurological outcomes. This dissociation between vasospasm-related morbidity and clinical outcomes associated with clazosentan therapy remains unclear and requires further investigation.
Journal of Neurosurgery