• Austin Lai, Can Ozan Tan, Justin Vranic, Stefan Weidauer, Thabele Leslie-Mazwi, Joshua A Hirsch, and Rajiv Gupta.
• Massachusetts General Hospital, Boston, MA, USA. austinhlai@gmail.com.
• Neurocrit Care. 2022 Feb 1; 36 (1): 240-247.

BackgroundClazosentan, an endothelin-1 receptor antagonist, has been shown to prevent the development of large vessel angiographic vasospasm after aneurysmal subarachnoid hemorrhage. We hypothesized that clazosentan can improve cerebral perfusion for territories affected by angiographically confirmed vasospasm.MethodsThe REVERSE study (REversal of Vasospasm with clazosEntan post-aneuRysmal Subarachnoid hEmorrhage) was a prospective multicenter open-label pilot study of adult patients with aneurysmal subarachnoid hemorrhage who received intravenous clazosentan after developing moderate to severe angiographic vasospasm. Using the radiographic data from the REVERSE study and additional retrospective radiographic data from our tertiary medical center, we compared the impact of intravenous clazosentan with intraarterial vasodilator therapy (medical standard of care) on vasospasm reversal using time to peak perfusion (TTPP; the time interval between the peak opacification of contrast dye in the main artery supplying an anatomically defined territory and the parenchymal phase when the dye is diffusely present in the brain parenchyma).ResultsBoth intravenous clazosentan (n = 7 vessels) and intraarterial vasodilator therapy (n = 11 vessels) resulted in a statistically significant improvement in TTPP at 24 h post intervention, when compared with the TTPP just prior to intervention for territories with angiographically confirmed severe vasospasm in the proximal arteries at baseline (linear mixed-effect model, p = 0.02). The clazosentan and intraarterial vasodilator therapy groups exhibited no statistically significant interaction term [time x treatment group (medical standard of care vs. clazosentan)] in our model (p = 0.71), suggesting similar temporal course of two therapies.ConclusionsIn our small pilot study, intravenous clazosentan administered for at least 24 h had an effect comparable with that of intraarterial vasodilator therapy in reversing angiographically confirmed severe vasospasm. Our results may indicate that clazosentan, in an appropriately selected patient cohort, could offer a noninvasive approach for alleviating vasospasm.© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.

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