Background: Sotatercept is an activin signaling inhibitor under investigation for PAH. Goal: Evaluate the prognostic utility of hemodynamic and cardiac function parameters in PAH patients receiving sotatercept vs placebo. Methods: Participants in STELLAR, a phase 3 trial (NCT04576988), were randomized 1:1 to sotatercept (0.3 up to 0.7 mg/kg once every 3 weeks) or placebo added to background therapies. Eligible participants had WHO functional class II-III, pulmonary vascular resistance ≥400 dyn·s·cm -5 , and 6-minute walk distance 150-550 m. This post-hoc analysis assessed clinical worsening events at last measurement by baseline echocardiography (ECHO), right heart catheterization (RHC), and NT-proBNP parameters. Clinical worsening events were assessed up to week 60. Uni-/multivariate-adjusted Cox models identified baseline parameters significantly (p<0.05) associated with events. Parameters with p-values <0.10 were carried forward to multivariate model. Receiver operating characteristic curves assessed discriminatory utility of cutoff values. Results: Of the significant univariate predictors, only study treatment and log2 NT-proBNP were significant independent predictors of clinical worsening in multivariate model (Table). Each unit increase in log2 NT-proBNP at baseline was associated with a 61% increase in risk (HR 1.61, 95% CI 1.39, 1.88; p<0.001). The AUC for log2 NT-proBNP (0.76 [95% CI 0.67, 0.85]) showed good performance. The optimal NT-proBNP cutoff value was 322 pg/mL. Sotatercept treatment was associated with an 81% reduction in risk vs placebo (HR 0.19, 95% CI 0.10 to 0.38; p<0.001), even after adjusting for NT-proBNP. Conclusions: This post-hoc analysis demonstrated that NT-proBNP is a strong predictor of clinical worsening events in PAH patients. Sotatercept treatment offered protection beyond that achieved with standard therapies alone, even after adjusting for the impact of NT-proBNP.
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