Efficacy and safety of sotatercept across ranges of cardiac index in patients with pulmonary arterial hypertension: A pooled analysis of PULSAR and STELLAR.

BACKGROUND

This analysis examined the effects of the activin signaling inhibitor, sotatercept, in pulmonary arterial hypertension (PAH) subgroups stratified by baseline cardiac index (CI).

METHODS

Pooled data from PULSAR (N = 106; NCT03496207) and STELLAR (N = 323; NCT04576988) were analyzed using 2 different CI thresholds, <2.0 and ≥2.0 liter/min/m as well as <2.5 and ≥2.5 liter/min/m. Median changes from baseline at week 24 were evaluated using Hodges-Lehmann estimator and least squares (LS) means, with 95% confidence intervals and p-values (significance: p = 0.05). Categorial endpoints and time-to-clinical worsening were analyzed by Cochran-Mantel-Haenszel and Cox model respectively.

RESULTS

Of 429 participants, 51 had CI <2.0 and 378 ≥2.0 liter/min/m, while 179 had CI <2.5 and 250 ≥2.5 liter/min/m. Sotatercept significantly improved median 6-minute walk distance (range: 33.9 to 63.7 m: p < 0.001), pulmonary vascular resistance (range: -202.8 to -395.4 dyn•s•cm; p ≤ 0.002), and N-terminal pro-B-type natriuretic peptide (range: -317.3 to -1,041.2 pg/ml; p < 0.001) across subgroups. LS means showed reductions in pulmonary and right atrial pressures, decreased right ventricular size, and improved tricuspid annular plane systolic excursion/systolic pulmonary artery pressure. Sotatercept delayed time to first occurrence of death or a worsening event for CI ≥2.5 (hazard ratio [HR] 0.12; p < 0.001), ≥2.0 (HR 0.13; p < 0.001), and <2.5 (HR 0.21; p < 0.001) liter/min/m. Improvements were observed in WHO functional class (all p < 0.050) and ESC/ERS risk scores (all p < 0.001).

CONCLUSIONS

Sotatercept demonstrated consistent efficacy and safety across CI subgroups, supporting its use in PAH patients irrespective of baseline cardiac hemodynamics.