Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: A total of 11 studies, including 10 published and one unpublished, comprising 8,469 patients were included in the meta-analysis.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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：动脉瘤性蛛网膜下腔出血（aSAH）是一种严重的事件，常并发脑血管痉挛（CV）。本研究旨在评估克拉佐坦的疗效和安全性，内皮素受体拮抗剂,在减少CV时，迟发性脑缺血(DCI),以及aSAH患者对抢救治疗的需求，同时评估其对功能结局和死亡率的影响。
方法：我们在多个数据库中进行了文献检索，以确定评估克拉佐坦在aSAH患者中的作用的相关研究。纳入队列研究和随机对照试验（RCTs）。主要结果是血管痉挛发生率，中度至重度血管痉挛，DCI，以及抢救治疗的需要。次要结果包括功能结果，死亡率,和不良事件。使用RevMan5.4软件将数据汇总为具有95%置信区间(CI)的风险比(R/R)。
结果：共11项研究，包括10个已出版和1个未出版，包括8,469例患者纳入荟萃分析。Clazosentan显着降低血管痉挛的发生率（R/R=0.49：0.34-0.70），中度至重度血管痉挛（R/R=0.53：0.46-0.61），DCI（R/R=0.70：0.59-0.82），与安慰剂相比，需要抢救治疗（R/R=0.65：0.52-0.83）。然而,在功能结局或死亡率方面未观察到显著改善.Clazosentan与肺部不良事件发生率增加相关(R/R=1.89:1.64-2.18),低血压（R/R=2.47：1.79-3.42），和贫血（R/R=1.49：1.23-1.79），但肝胆不良事件或脑出血的风险没有增加。
结论：Clazosentan在减轻血管痉挛方面具有疗效，中度至重度血管痉挛，DCI，以及aSAH患者对抢救治疗的需求，但不能显著改善功能结局或死亡率.虽然与特定的不良事件相关，克拉佐坦可能是一种有价值的辅助治疗aSAH，特别是在血管痉挛的高危人群中。
方法：我们在多个数据库中进行了文献检索，以确定评估克拉佐坦在aSAH患者中的作用的相关研究。纳入队列研究和随机对照试验（RCTs）。主要结果是血管痉挛发生率，中度至重度血管痉挛，DCI，以及抢救治疗的需要。次要结果包括功能结果，死亡率,和不良事件。使用RevMan5.4软件将数据汇总为具有95%置信区间(CI)的风险比(R/R)。
结果：共11项研究，包括10个已出版和1个未出版，包括8,469例患者纳入荟萃分析。Clazosentan显着降低血管痉挛的发生率（R/R=0.49：0.34-0.70），中度至重度血管痉挛（R/R=0.53：0.46-0.61），DCI（R/R=0.70：0.59-0.82），与安慰剂相比，需要抢救治疗（R/R=0.65：0.52-0.83）。然而,在功能结局或死亡率方面未观察到显著改善.Clazosentan与肺部不良事件发生率增加相关(R/R=1.89:1.64-2.18),低血压（R/R=2.47：1.79-3.42），和贫血（R/R=1.49：1.23-1.79），但肝胆不良事件或脑出血的风险没有增加。
结论：Clazosentan在减轻血管痉挛方面具有疗效，中度至重度血管痉挛，DCI，以及aSAH患者对抢救治疗的需求，但不能显著改善功能结局或死亡率.虽然与特定的不良事件相关，克拉佐坦可能是一种有价值的辅助治疗aSAH，特别是在血管痉挛的高危人群中。
