Real-world data of clazosentan in combination therapy for aneurysmal subarachnoid hemorrhage: a multicenter retrospective cohort study

Abstract

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.

Keywords: Aneurysmal subarachnoid hemorrhage; Clazosentan; Delayed cerebral ischemia; Fasudil; Prognosis; Vasospasm.