Efficacy of combined clazosentan and cilostazol therapy for cerebral vasospasm after subarachnoid hemorrhage: a retrospective multicenter registry study.

Abstract

Objective: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) is associated with a poor prognosis. Since 2022, clazosentan has become available for clinical use in Japan and has shown potential in improving clinical outcomes for patients with aSAH. However, whether clazosentan alone is sufficient to achieve optimal results or combination therapy is required remains unclear. In this study, the authors aimed to assess the efficacy of combining clazosentan and cilostazol for treating cerebral vasospasm following aSAH due to a ruptured cerebral aneurysm.

Methods: This retrospective multicenter study was conducted using repository data from April 2023 to March 2024 from across 20 institutes. Patients who underwent coil embolization or surgical clipping within 48 hours of aSAH and had a preoperative modified Rankin Scale (mRS) score of 0-2 were eligible for inclusion in the study. Patients who received clazosentan plus fasudil were excluded. The patients were divided into two groups: those who received clazosentan plus cilostazol (cilostazol combination group) and those who did not receive cilostazol (noncilostazol group). Outcomes were measured based on discharge mRS scores (primary) and complications (secondary), including cerebral vasospasm, delayed cerebral ischemia (DCI), pulmonary complications, hypotension, cerebral edema, and de novo intracranial hemorrhage.

Results: In total, 161 patients were included in this study, with 94 and 67 patients in the cilostazol combination and noncilostazol groups, respectively. No significant difference was observed between the two groups in terms of optimal outcomes at discharge (mRS score 0-2). However, the cilostazol combination group tended to experience a lower rate of poor outcomes than the noncilostazol group (11.7% vs 14.9%, respectively, OR 0.36, 95% CI 0.11-1.2, p = 0.095). The incidence rate of DCI was significantly lower in the cilostazol combination group than in the noncilostazol group (0.0% vs 7.5%, p = 0.02). No significant differences were found between the two groups with respect to other complications.

Conclusions: The combination of clazosentan and cilostazol may reduce the incidence of DCI, although its impact on functional outcomes remains unclear. Further research is warranted to explore effective pharmacological strategies for improving the prognosis of aSAH.