The effectiveness and safety of clazosentan in treating aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.

• The meta -analysis included 11 studies (7 RCTs and 4 cohort studies) with varied geographical representation and patient demographics. Most studies were rated as having low to moderate risk of bias. However, some outcomes displayed heterogeneity, which was addressed through sensitivity analyses to ensure robust results. • Clazosentan significantly reduces the incidence of vasospasm, including moderate to severe vasospasm, and delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH). The risk ratios for vasospasm, moderate to severe vasospasm, and DCI were 0.49, 0.53, and 0.70 respectively, indicating a substantial reduction compared to placebo. • The use of clazosentan significantly lowers the need for rescue therapy among aSAH patients. The pooled analysis showed a risk ratio of 0.65, suggesting a 35 % reduction in the requirement for additional interventions. • Clazosentan is associated with increased rates of specific adverse events such as pulmonary complications (RR = 1.89), hypotension (RR = 2.47), and anemia (RR = 1.49). However, it does not increase the risk of hepatobiliary adverse events or cerebral hemorrhage. • Despite its efficacy in reducing vasospasm and DCI, clazosentan does not show a significant improvement in functional outcomes (measured by GOSE and mRS) or mortality rates. This suggests that while it mitigates certain complications, it does not necessarily enhance overall survival or recovery quality. Aneurysmal subarachnoid hemorrhage (aSAH) is a severe event often complicated by cerebral vasospasm (CV). This study aimed to assess the efficacy and safety of clazosentan, an endothelin receptor antagonist, in reducing CV, delayed cerebral ischemia (DCI), and the need for rescue therapy in aSAH patients, while evaluating its impact on functional outcomes and mortality. We conducted a literature search across multiple databases to identify relevant studies evaluating the effects of clazosentan in aSAH patients. Both cohort studies and randomized controlled trials (RCTs) were included. The primary outcomes were vasospasm incidence, moderate to severe vasospasm, DCI, and the need for rescue therapy. Secondary outcomes included functional outcomes, mortality, and adverse events. The data were pooled as Risk ratios (R/R) with 95 % confidence intervals (CI) using RevMan 5.4 software. A total of 11 studies, including 10 published and one unpublished, comprising 8,469 patients were included in the meta -analysis. Clazosentan significantly reduced the incidence of vasospasm (R/R = 0.49: 0.34–0.70), moderate to severe vasospasm (R/R = 0.53: 0.46–0.61), DCI (R/R = 0.70: 0.59–0.82), and the need for rescue therapy (R/R = 0.65: 0.52–0.83) compared to placebo. However, no significant improvement in functional outcomes or mortality rates was observed. Clazosentan was associated with increased rates of pulmonary adverse events (R/R = 1.89: 1.64–2.18), hypotension (R/R = 2.47: 1.79–3.42), and anemia (R/R = 1.49: 1.23–1.79) but no increased risk of hepatobiliary adverse events or cerebral hemorrhage. Clazosentan demonstrates efficacy in reducing vasospasm, moderate to severe vasospasm, DCI, and the need for rescue therapy in aSAH patients, but does not significantly improve functional outcomes or mortality rates. While associated with specific adverse events, clazosentan may be a valuable adjunctive therapy in the management of aSAH, particularly in a high-risk population for vasospasm. [ABSTRACT FROM AUTHOR]