Clinical factors associated with delayed ischemic and non-ischemic adverse events in clazosentan therapy after aneurysmal subarachnoid hemorrhage: early insights from a multicenter prospective registry.

Abstract

Clazosentan (CLZ) therapy prevents delayed ischemia following aneurysmal subarachnoid hemorrhage (aSAH), but non-ischemic adverse events necessitate optimized protocols. This study presents outcomes of contemporary CLZ therapy under a unified protocol and identifies factors influencing delayed ischemic and non-ischemic adverse events following aSAH. This multicenter prospective registry analyzed data from 80 aSAH patients receiving CLZ therapy (April 2023 - October 2024). Primary endpoints were delayed ischemic events and non-ischemic adverse events; secondary endpoint was favorable outcome (modified Rankin Scale 0-2) at discharge or six weeks post-onset. Delayed ischemic events occurred in 19 patients (23.8%), including delayed ischemic neurological deterioration (8.8%), moderate-to-severe cerebral vasospasm (20.0%), and symptomatic delayed cerebral infarction (7.5%). Non-ischemic adverse events were observed in 22 patients (27.5%). Favorable outcomes were achieved in 52 patients (65.0%). Delayed ischemic events were associated with female sex, poor severity grades, higher Fischer scale scores, and elevated neutrophil-to-lymphocyte ratios. Non-ischemic adverse events were associated with older age, anemia, hypoproteinemia, and elevated cardiothoracic ratios. Multivariate analysis identified non-ischemic adverse events as significant for unfavorable outcomes (FDR p <.001), whereas delayed ischemic events were not (FDR p =.705). Among non-ischemic adverse events, pulmonary edema was the strongest factor associated with unfavorable outcomes. In conclusion, CLZ therapy with appropriate candidate selection and management protocol appears promising as a treatment option to prevent delayed ischemia after aSAH, though potential confounders warrant careful consideration. Addressing clinical risk factors for non-ischemic adverse events may further enhance treatment outcomes. Clinical trial number Not applicable.