Effectiveness of clazosentan in aneurysmal subarachnoid hemorrhage: A 12-year multicenter real-world study

Objective Outcomes of aneurysmal subarachnoid hemorrhage (SAH) remain poor. This study aimed to investigate changes in outcomes before and after the introduction of an endothelin A receptor antagonist clazosentan to prevent delayed cerebral ischemia (DCI), and to identify factors that influence outcomes in actual clinical practice. Methods The study included 1,097 SAH patients (median age, 65.0 years; admission World Federation of Neurological Surgeons [WFNS] grade V, 247 patients [22.5%]) who were prospectively registered in nine primary stroke centers in Mie prefecture, Japan, and had aneurysm obliteration within 48 h of onset. Outcomes (3-month modified Rankin Scale [mRS]) were retrospectively compared among the Early (May 2013–October 2019), Pre-clazosentan (November 2019–May 2022), and Clazosentan (June 2022–December 2024) periods, and outcome-determining factors, including medications, were investigated using inverse probability of treatment weighting-based sensitivity analysis and multivariable adjustment. Results Good outcomes (3-month mRS 0–2) were achieved in 652 patients (59.4%). During the period when fasudil, a Rho-kinase inhibitor, was used as the primary DCI treatment, patients with good outcomes decreased over time, but increased after the introduction of clazosentan. Although patients treated with clazosentan were younger and had better admission WFNS grades, the treatment effect was similar even in patients aged 76 years or older, or those with WFNS grade V. In multivariable analyses, among medications used to prevent DCI, clazosentan showed the strongest association with a reduced risk of poor outcome (adjusted risk ratio, 0.71; 95% confidence interval, 0.53–0.95), followed by fasudil (adjusted risk ratio, 0.75; 95% confidence interval, 0.62–0.91). Conclusion These findings suggest that clazosentan use may improve the treatment outcomes of patients with SAH in certain regions, regardless of age or WFNS grade.