Clazosentan's dual edge in managing vasospasm following aneurysmal subarachnoid hemorrhage: an updated systematic review, meta-analysis, and meta-regression of clinical outcomes and safety profiles.

Abstract

Aneurysmal Subarachnoid Hemorrhage (aSAH), resulting from ruptured aneurysms, is a major contributor to stroke-related mortality and morbidity. Despite advances in healthcare, aSAH remains severe and often leads to complications such as cerebral vasospasm (CV), cerebral infarction, and delayed ischemic neurological deficits (DIND). Clazosentan, an endothelin receptor antagonist, has demonstrated potential in alleviating vasospasm and its associated outcomes, although evidence of its efficacy remains unclear. A systematic review and meta-analysis was conducted following the PRISMA guidelines, including randomized controlled trials (RCTs) that compared clazosentan with placebo in adult patients with aSAH. Primary outcomes were vasospasm-related cerebral infarction and DIND. Secondary outcomes included the incidence of vasospasm, mortality, and adverse effects. Data were analyzed using Review Manager 5.3, and meta-regression was employed to assess moderators, including aneurysm treatment modality. Eight RCTs, involving 3,186 participants, were included in the analysis. Clazosentan significantly reduced vasospasm-related cerebral infarction (RR = 0.56, 95% CI: 0.42-0.76, p = 0.0002) and DIND (RR = 0.67, 95% CI: 0.55-0.80, p < 0.0001). Dosages of 10 mg and 15 mg were found to be the most effective. However, clazosentan had no effect on the overall mortality (p = 0.48) and was associated with an increased risk of hypotension, pulmonary edema, and pleural effusion. Clazosentan significantly reduced vasospasm-related cerebral infarction and DIND in patients with aSAH, particularly at higher doses. Nonetheless, its use is linked to notable adverse effects, highlighting the need for careful assessment of its risk-benefit profile in clinical practice.