Factors Influencing Discontinuation of Clazosentan Therapy in Elderly Patients with Aneurysmal Subarachnoid Hemorrhage: A Retrospective Study from a Japanese Single Center.

Autor:	Mutoh T; Department of Surgical Neurology, Research Institute for Brain and Blood Vessels, Akita Cerebrospinal and Cardiovascular Center, Akita, Japan., Aono H; Department of Surgical Neurology, Research Institute for Brain and Blood Vessels, Akita Cerebrospinal and Cardiovascular Center, Akita, Japan., Seto W; Department of Pharmaceutics, Akita Cerebrospinal and Cardiovascular Center, Akita, Japan., Kimoto T; Department of Pharmaceutics, Akita Cerebrospinal and Cardiovascular Center, Akita, Japan., Tochinai R; Department of Veterinary Pathophysiology and Animal Health, Graduate School of Agriculture and Life Sciences, the University of Tokyo, Tokyo, Japan., Moroi J; Department of Surgical Neurology, Research Institute for Brain and Blood Vessels, Akita Cerebrospinal and Cardiovascular Center, Akita, Japan., Ishikawa T; Department of Surgical Neurology, Research Institute for Brain and Blood Vessels, Akita Cerebrospinal and Cardiovascular Center, Akita, Japan.
Jazyk:	angličtina
Zdroj:	Medical science monitor : international medical journal of experimental and clinical research [Med Sci Monit] 2024 Feb 16; Vol. 30, pp. e943303. Date of Electronic Publication: 2024 Feb 16.
DOI:	10.12659/MSM.943303
Abstrakt:	BACKGROUND Clazosentan is an endothelin receptor antagonist approved in Japan for preventing cerebral vasospasm and vasospasm-associated cerebral ischemia and infarction. This study included elderly patients aged ≥75 years with aneurysmal subarachnoid hemorrhage (SAH) and aimed to evaluate the factors associated with discontinuing anti-vasospasm therapy with clazosentan. MATERIAL AND METHODS In this single-center retrospective observational study, we extracted diagnostic and therapeutic work-up data of consecutive 40 patients with SAH treated with clazosentan infusion (10 mg/h) as first-line anti-vasospasm therapy between May 2022 and August 2023. Patient data were compared between the discontinued and completed groups, and related factors for the discontinuation were further analyzed. RESULTS Clazosentan was discontinued in 22% (n=9) of patients due to intolerable dyspnea accompanied by hypoxemia at 5±3 days after therapy initiation, in which 44% (n=4) were elderly (≥75 years). Patients who discontinued clazosentan therapy showed significantly lower urine volumes compared with those who completed the therapy (P<0.05). Multivariate regression analysis revealed that day-to-day urine volume variance and older age were independent risk factors for drug cessation (P<0.05). The cut-off value for predicting clazosentan discontinuation was -0.7 mL/kg/h with sensitivity of 86% and specificity of 75% (area under the curve: 0.76±0.10; 95% confidence interval: 0.56-0.96; P=0.035). CONCLUSIONS Our results suggest that approximately 20% of SAH patients suffered from intolerable respiratory symptoms attributable to hypoxemia. We found that both reduced day-to-day urine volume variation and older age are independent risk factors for drug discontinuation.
Databáze:	MEDLINE
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