Department of Neurosurgery, Kariya Toyota General Hospital, Kariya, Aichi, Japan.
Department of Neurosurgery, Handa City Hospital, Handa, Aichi, Japan.
Neurosurg Rev. 2023 Aug 9;46(1):195. doi: 10.1007/s10143-023-02104-2.
Aneurysmal subarachnoid hemorrhage (aSAH) may lead to cerebral vasospasm, significantly associated with morbidity and mortality. In double-blind, placebo-controlled phase 3 studies, clazosentan reduces cerebral vasospasm-related morbidity and all-cause mortality in patients with aSAH. There are no reports about the clinical efficacy of clazosentan combination therapy with some other drugs. Initially, we explored the efficacy of clazosentan combination therapy with cilostazol, statin, and antiepileptic drugs. Subsequently, we assessed the add-on effect of fasudil to clazosentan combination therapy for aSAH patients. This multicenter, retrospective, observational cohort study included Japanese patients with aSAH between June 2022 and March 2023. The primary outcome was the ordinal score on the modified Rankin Scale (mRS; range, 0-6, with elevated scores indicating greater disability) at discharge. Among the 47 cases (women 74.5%; age 64.4 ± 15.0 years) undergoing clazosentan combination therapy, 29 (61.7%) resulted in favorable outcomes. Overall, vasospasm occurred in 16 cases (34.0%), with four cases (8.5%) developing vasospasm-related delayed cerebral ischemia (DCI). Both hypotension and vasospasm-related DCI were related to unfavorable outcome at discharge. Fasudil were added in 18 (38.3%) cases. Despite adding fasudil to clazosentan combination therapy, the incidence of aSAH-related vasospasm did not decrease. Added-on fasudil to combination therapy related to pulmonary edema, vasospasm, and vasospasm-related DCI, and unfavorable outcomes. Clazosentan combination therapy could potentially result in favorable outcomes for aSAH patients to prevent post-aSAH vasospasm-related DCI. The add-on effect of fasudil to combination therapy did not demonstrate a significant impact in reducing aSAH-related vasospasm or improving outcomes at discharge.
颅内动脉瘤性蛛网膜下腔出血（aSAH）可能导致脑血管痉挛，与发病率和死亡率密切相关。在双盲、安慰剂对照的 3 期研究中，氯苯唑酸可降低 aSAH 患者脑血管痉挛相关发病率和全因死亡率。目前尚无氯苯唑酸联合其他药物治疗的临床疗效报道。最初，我们探索了氯苯唑酸联合西洛他唑、他汀类药物和抗癫痫药物的疗效。随后，我们评估了法舒地尔对 aSAH 患者氯苯唑酸联合治疗的附加作用。这项多中心、回顾性、观察性队列研究纳入了 2022 年 6 月至 2023 年 3 月期间的日本 aSAH 患者。主要结局是出院时改良Rankin 量表（mRS；范围 0-6，得分越高表示残疾程度越高）的等级评分。在接受氯苯唑酸联合治疗的 47 例患者（女性 74.5%；年龄 64.4±15.0 岁）中，29 例（61.7%）结果良好。总体而言，16 例（34.0%）发生血管痉挛，4 例（8.5%）发生与血管痉挛相关的迟发性脑缺血（DCI）。低血压和与血管痉挛相关的 DCI 均与出院时的不良结局相关。18 例（38.3%）患者加用法舒地尔。尽管在氯苯唑酸联合治疗中加用法舒地尔，但 aSAH 相关血管痉挛的发生率并未降低。加用法舒地尔与肺水肿、血管痉挛和与血管痉挛相关的 DCI 以及不良结局相关。氯苯唑酸联合治疗可能对预防 aSAH 后血管痉挛相关 DCI 导致的 aSAH 患者有良好的结局。法舒地尔对联合治疗的附加作用并未显示出在降低 aSAH 相关血管痉挛或改善出院结局方面的显著影响。
