Background. Pulmonary arterial hypertension (PAH) is characterized by high morbidity and mortality despite current vasodilator therapies. Sotatercept, a fusion protein targeting the activin signaling pathway, improved exercise capacity and reduced clinical worsening in PAH patients in the STELLAR randomized controlled trial (RCT). This study explored the eligibility for sotatercept in a real-world PAH population based on the STELLAR trial criteria. Methods. We retrospectively analyzed 657 patients with incident PAH (2001–2024), excluding 116 with incomplete follow-up data. Inclusion criteria mirrored STELLAR were WHO functional class II/III, PVR ≥5 WU, and stable PAH therapy. Exclusion criteria were severe comorbidities, or recent cardiovascular events. Baseline and follow-up risk were assessed using ESC/ERS tools. Statistical analyses included univariate and multivariate models to explore the factors more strongly associated with eligibility/non-eligibility. Results. Of 541 patients analyzed, 437 (81%) were initially eligible. Non-eligibility (19%) was mainly due to non-permitted PAH subtypes (71%) or positive vasoreactivity (29%). Eligible and non-eligible groups were demographically similar; however, congenital heart disease-associated PAH was more common in eligible patients (8% vs. 2%, p<0.001). During a median follow-up of 45 months, 50% remained eligible, with exclusion primarily due to mild hemodynamic impairment (e.g., PVR <5 WU, 53%) or recent treatment variation (53%). Predictors of non-eligibility included older age (HR 1.011, p=0.003) and triple therapy combination (HR 2.841, p<0.001), while idiopathic PAH was associated with lower probability of non-eligibility (HR 0.742, p=0.025). Conclusion. STELLAR eligibility criteria exclude a substantial portion of real-world PAH patients, particularly during follow-up. Tailored selection strategies and clear definition of the appropriate timing are needed to maximize the clinical applicability of Sotatercept and better address unmet needs in PAH management.
Associazione Nazionale Medici Cardiologi Ospedalieri
