Evaluating clazosentan sodium for the treatment of aneurysmal subarachnoid hemorrhage

Area of Science:

• Neurology
• Pharmacology
• Critical Care Medicine

Background:

• Delayed cerebral ischemia (DCI) is a significant cause of mortality and morbidity following aneurysmal subarachnoid hemorrhage (aSAH).
• Nimodipine is the sole FDA-approved medication for DCI prevention, highlighting the need for alternative therapeutic strategies.
• Cerebral vasospasm is a primary contributor to DCI, necessitating targeted interventions.

Purpose of the Study:

• To review clazosentan, a selective endothelin-A receptor antagonist, for its efficacy and safety in preventing DCI after aSAH.
• To synthesize evidence from clinical trials and real-world data on clazosentan's role in managing cerebral vasospasm and DCI.
• To evaluate clazosentan's potential as an adjunct therapy in specific patient populations.

Main Methods:

• Comprehensive literature search of PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar up to March 2025.
• Inclusion of Phase I-IV clinical studies, pharmacokinetic/pharmacodynamic studies, and meta-analyses focusing on clazosentan, aSAH, and DCI.
• Exclusion of preclinical reports and non-peer-reviewed abstracts, prioritizing randomized controlled trials and large-scale syntheses.

Main Results:

• Clazosentan demonstrates consistent reduction in angiographic vasospasm and related complications.
• Improvements in functional outcomes with clazosentan have been inconsistent across international trials.
• Safety concerns include pulmonary complications, anemia, and fluid retention, requiring careful patient monitoring.

Conclusions:

• Clazosentan shows promise as an adjunct to standard care for DCI prevention in selected patient groups and settings.
• Further research is needed to optimize clazosentan dosing, patient selection, and combination strategies.
• Addressing microvascular dysfunction and neuroinflammation beyond large-vessel spasm is critical for improving DCI management.