Evaluating clazosentan sodium for the treatment of aneurysmal subarachnoid hemorrhage.

Abstract

Introduction: Delayed cerebral ischemia (DCI), often linked to cerebral vasospasm, is a major cause of death and disability after aneurysmal subarachnoid hemorrhage (aSAH). Nimodipine remains the only Food and Drug Administration (FDA)-approved drug for DCI prevention.

Areas covered: The authors review clazosentan, a selective endothelin-A receptor antagonist approved in Japan and South Korea. This drug profile is based on searches utilizing PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar from database inception through to March 2025 using terms including 'clazosentan,' 'aneurysmal subarachnoid hemorrhage,' 'cerebral vasospasm,' 'delayed cerebral ischemia,' and trial identifiers (CONSCIOUS, REACT, REVERSE). The authors included Phase I-IV clinical studies, PK/PD studies, and meta-analyses; preclinical reports and non-peer-reviewed abstracts were excluded, prioritizing randomized controlled trials and large syntheses.

Expert opinion: Clazosentan consistently reduces angiographic vasospasm and vasospasm-related complications, yet durable improvements in functional outcomes have been inconsistent across international trials. Safety concerns like pulmonary complications, anemia, and fluid retention require vigilant monitoring, particularly in elderly or hepatically impaired patients. Recent Japanese Phase III trials and real-world cohorts suggest benefit in selected populations and practice settings, supporting clazosentan as an adjunct to standard care rather than a replacement. Further work should refine dosing, patient selection, and combination strategies that target microvascular dysfunction and neuroinflammation beyond large-vessel spasm.