Prognosis-anchored outcome evaluation (PAOE) for detecting functional benefit in aSAH: A multicenter analysis of clazosentan use

IF 1.8 4区医学 Q3 CLINICAL NEUROLOGY

Journal of Clinical Neuroscience Pub Date : 2025-08-16 DOI:10.1016/j.jocn.2025.111552

Atsushi Sato , Naomichi Wada , Takehiro Yako , Akihiro Nishikawa , Takahiro Murata , Tatsuya Seguchi , Yuki Inomata , Yasunaga Yamamoto , Toshihiro Ogiwara , Yoshiki Hanaoka , Mana Wakabayashi , Kazuhiro Hongo , Tetsuyoshi Horiuchi

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引用次数: 0

Abstract

Background

Although clazosentan has shown vasospasm-reducing effects in aneurysmal subarachnoid hemorrhage (aSAH), its impact on long-term functional outcomes remains controversial. Conventional randomized trials have reported limited benefits. This study applies Prognosis-Anchored Outcome Evaluation (PAOE), a model-based framework comparing observed outcomes to individualized prognostic expectations, to assess potential functional benefit in real-world practice.

Methods

We prospectively analyzed 331 aSAH patients across eight institutions. Predicted 3-month modified Rankin Scale (pmRS) scores were calculated using a validated prognostic model (S-Score). Observed outcomes (final mRS) were compared with pmRS to quantify individual-level benefit. Patients were grouped by clazosentan use. Subgroup analyses were performed by pmRS strata and surgical treatment status.

Results

The average pmRS did not differ significantly between groups. However, clazosentan-treated patients showed a greater frequency of favorable outcomes (final mRS ≤ 2) than predicted, particularly in the intermediate prognostic range (pmRS 3–5). A subanalysis limited to patients receiving definitive aneurysm treatment demonstrated significantly improved outcomes in the clazosentan group within pmRS 3–4 and 4–5 strata (p < 0.05 and p < 0.05, respectively). These findings suggest a targeted treatment-responsive zone.

Conclusions

PAOE provides a complementary approach to traditional cohort or RCT analyses by accounting for individual prognostic expectations. Our findings support the hypothesis that clazosentan may offer functional benefit in selected aSAH patients with moderate predicted disability. This approach may help identify patients who are most likely to benefit from vasospasm-targeted interventions in clinical practice.

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用于检测aSAH功能获益的预后锚定结果评估（PAOE）：一项对克拉生坦使用的多中心分析

虽然克拉生坦在动脉瘤性蛛网膜下腔出血（aSAH）中显示出血管痉挛减少作用，但其对长期功能结局的影响仍存在争议。传统的随机试验报告的疗效有限。本研究采用预后锚定结果评估（PAOE），这是一种基于模型的框架，将观察到的结果与个性化的预后预期进行比较，以评估现实世界实践中潜在的功能益处。方法对来自8家机构的331例aSAH患者进行前瞻性分析。使用经过验证的预后模型（S-Score）计算预测的3个月修正Rankin量表（pmRS）评分。将观察结果（最终mRS）与预mRS进行比较，以量化个人水平的获益。患者按克拉生坦的使用进行分组。按pmr分层和手术治疗情况进行亚组分析。结果两组间平均pmr差异无统计学意义。然而，clazostan治疗的患者出现良好结果（最终mRS≤2）的频率高于预期，特别是在中间预后范围（pmRS 3-5）。一项局限于接受明确动脉瘤治疗的患者的亚分析显示，clazosentan组在pmRS 3-4和4-5层内的预后显著改善(p <；0.05和p <；分别为0.05)。这些发现表明存在靶向治疗反应区。结论：spaoe通过考虑个体预后预期，为传统队列或RCT分析提供了一种补充方法。我们的研究结果支持了这样的假设，即克唑生坦可能对部分预测为中度残疾的aSAH患者提供功能益处。这种方法可能有助于确定在临床实践中最有可能从血管痉挛靶向干预中获益的患者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Neuroscience 医学-临床神经学

CiteScore

4.50

自引率

0.00%

发文量

402

审稿时长

40 days

期刊介绍： This International journal, Journal of Clinical Neuroscience, publishes articles on clinical neurosurgery and neurology and the related neurosciences such as neuro-pathology, neuro-radiology, neuro-ophthalmology and neuro-physiology. The journal has a broad International perspective, and emphasises the advances occurring in Asia, the Pacific Rim region, Europe and North America. The Journal acts as a focus for publication of major clinical and laboratory research, as well as publishing solicited manuscripts on specific subjects from experts, case reports and other information of interest to clinicians working in the clinical neurosciences.