Addition of Clazosentan to Fasudil Is Associated with Increased Cerebral Blood Volume without Changes in Cerebral Blood Flow after Aneurysmal Subarachnoid Hemorrhage: A CT Perfusion Study.

Abstract

Clazosentan, an endothelin receptor antagonist, is used to prevent cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH); however, its effects on the cerebral microcirculation remain unclear. This study evaluated clazosentan-associated hemodynamic changes using computed tomography perfusion (CTP). We retrospectively analyzed 67 patients with aSAH treated between January 2020 and March 2025. Patients received either fasudil alone or fasudil plus clazosentan. Relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative mean transit time (rMTT) were calculated from serial CTP examinations. A linear mixed-effects model included patient ID as a random effect and treatment group, number of CTP examinations, brain region, age, treatment modality, and radiographic vasospasm as fixed effects. A total of 98 CTP examinations were analyzed. rCBV was significantly higher in the fasudil + clazosentan group in both the peripheral cortical and basal ganglia regions, whereas no significant between-group differences were observed in rCBF or rMTT. In the mixed-effects model, the addition of clazosentan remained significantly associated with increased rCBV (estimated difference = 0.172, P = 0.008). No significant interactions with brain region or number of CTP examinations were observed. rCBV was not significantly associated with a favorable functional outcome at 3 months (P = 0.092). The addition of clazosentan to fasudil was associated with increased cerebral blood volume, without significant changes in cerebral blood flow or mean transit time. These findings may be consistent with altered microvascular capacitance but should not be interpreted as evidence of improved tissue perfusion or clinical outcomes.