Clazosentan for cerebral vasospasm prevention in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating neurological emergency, with cerebral vasospasm contributing significantly to poor outcomes. Clazosentan, a selective endothelin-A receptor antagonist, has shown potential in preventing vasospasm, though its overall efficacy and safety profile require comprehensive assessment. We conducted a systematic review and meta-analysis following PRISMA guidelines, searching multiple databases through March 2025. We included randomized controlled trials and observational studies comparing clazosentan with placebo or active controls in aSAH patients. Outcomes included vasospasm incidence, its complications, and adverse events. Analysis of 13 reports (n = 5,728) were included. Compared to placebo, clazosentan significantly reduced vasospasm-related cerebral infarcts (RR: 0.56, p = 0.0002), delayed ischemic neurological deficits (DIND) (RR: 0.67, p < 0.0001), and the incidence of vasospasm (RR: 0.54, p < 0.00001). Compared to fasudil, clazosentan was associated with a lower incidence of vasospasm (RR: 0.44, p = 0.0004) and vasospasm-related cerebral infarcts (RR: 0.27, p = 0.002), but no significant difference was observed in DIND (p = 0.89). The drug showed particular benefit at higher doses (10–15 mg/h) and in surgical clipping patients. Clazosentan use was linked to a higher risk of adverse events, including pulmonary complications and hypotension (p < 0.05). While clazosentan effectively prevents cerebral vasospasm following aSAH, particularly at higher doses in surgically treated patients, its clinical utility must be weighed against significant systemic adverse effects. These findings support selective use in high-risk patients while highlighting the need for careful monitoring and individualized treatment approaches.