Comparison of efficacy between clazosentan and fasudil hydrochloride-based management of vasospasm after subarachnoid hemorrhage focusing on older and WFNS grade V patients: a single-center experience in Japan

Abstract

Subarachnoid hemorrhage often leads to poor outcomes owing to vasospasm, even after successful aneurysm treatment. Clazosentan, an endothelin receptor inhibitor, has been proven to be an effective treatment for vasospasms in a Japanese randomized controlled trial. However, its efficacy in older patients (≥ 75 years old) and those with World Federation of Neurosurgical Societies (WFNS) grade V has not been demonstrated. We retrospectively evaluated the efficacy of clazosentan in older patients and those with WFNS grade V, using real-world data. Patients with subarachnoid hemorrhage treated before and after the introduction of clazosentan were retrospectively evaluated. The patients were categorized into two groups (clazosentan era versus pre-clazosentan era), in which vasospasm management and outcomes were compared. Vasospasms were managed with fasudil hydrochloride-based (pre-clazosentan era) or clazosentan-based treatment (clazosentan era). Seventy-eight patients were included in this study: the clazosentan era (n = 32) and pre-clazosentan era (n = 46). Overall, clazosentan significantly reduced clinical vasospasms (clazosentan era: 31.3% versus pre-clazosentan era: 60.9%, p = 0.01), delayed cerebral ischemia (DCI) (9.4% versus 39.1%, p = 0.004), and vasospasm-related morbidity and mortality (M/M) (3.1% versus 19.6%, p = 0.03). In subgroup analysis of older patients or those with WFNS grade V, no significant difference was observed in clinical outcomes, although both DCI and vasospasm-related M/M were lower in the clazosentan era. Clazosentan was more effective than fasudil-based management in preventing DCI and reducing vasospasm-related M/M. Clazosentan could be used safely in older patients and those with WFNS grade V, although clinical outcomes in these patients were comparable to those of conventional treatment.

Keywords: Endothelin; Endothelin a receptor antagonists; Endovascular aneurysm repair; Subarachnoid hemorrhage; Vasospasm.