Quantitative evaluation of the vasodilatory effect of clazosentan in preventing cerebral vasospasm after subarachnoid hemorrhage.

Abstract

Background and PurposeAlthough many studies have reported the efficacy of clazosentan in preventing delayed cerebral ischemia associated with cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH), recent studies have shown that its vasodilatory effect does not contribute to improved prognosis, leaving its efficacy controversial. In this study, we quantitatively measured vascular diameter changes during the vasospasm period at various vascular sites to investigate the association between the radiological and clinical effects of clazosentan.Materials and MethodsWe retrospectively analyzed 22 patients with aSAH classified as Fisher group 3, treated at our hospital. Clazosentan (10 mg/h) was administered to 12 patients, while 10 patients received conventional vasospasm management. Arterial diameters at 12 locations were measured at the onset and during the vasospasm period. Quantitative changes in vascular diameter were compared between the clazosentan and nonclazosentan groups.ResultsDuring the vasospasm period, mean arterial diameters increased in all regions, including the posterior circulation, except internal carotid artery (ICA) top in the clazosentan group, while they decreased across all regions in the nonclazosentan group (overall average: + 22.3% vs. -16.9%; p = 0.005). Notably, in the clazosentan group, significant vasodilation was observed in distal arteries (M2: + 46.1%, p = 0.003; M3: + 58.2%, p = 0.001) compared to proximal arteries (ICAtop: -10.7%, p = 0.33; M1p: + 0.38%, p = 0.16; M1d: + 3.6%, p = 0.07). Symptomatic vasospasm occurred exclusively in the nonclazosentan group; however, no significant difference was observed in modified Rankin Scale scores 3 months post-onset (p = 0.38).ConclusionsClazosentan demonstrated a significant vasodilatory effect compared to conventional treatments, particularly in distal arteries. However, its limited effect on proximal arteries suggests a need for supplementary treatments targeting these regions to improve clinical outcomes. Differences in vasodilatory effect at various sites may be associated with the controversy regarding clazosentan's clinical effects.