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

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.

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.

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.

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.