The European Respiratory Society (ERS) has released an updated guideline for pulmonary arterial hypertension (PAH) treatment, endorsing sotatercept (Winrevair; Merck & Co.) as an additional therapy for patients already on background treatment, marking a significant shift in PAH management.
This change is significant for pharmacists, as it introduces a first-in-class biologic with a distinct adverse event profile, new monitoring demands, and counseling needs that differ from the oral and infused therapies that have long defined PAH management.
The 2022 ESC/ERS guidelines built PAH pharmacotherapy around three established pathways: the endothelin pathway, the nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate (NO-sGC-cGMP) pathway, and the prostacyclin pathway. The 2026 update extends this framework, with sotatercept targeting a fourth pathway as a fusion protein that rebalances pro- and antiproliferative signaling implicated in pulmonary vascular remodeling.
The Task Force issued a strong recommendation, backed by high certainty of evidence, for add-on sotatercept in patients with PAH who are already receiving PAH drugs and are at intermediate-low, intermediate-high, or high risk of death during follow-up.
The recommendation rests on four randomized controlled trials: PULSAR, STELLAR, ZENITH, and HYPERION. In the STELLAR trial, adding sotatercept to stable background therapy improved 6-minute walk distance by 40.8 m versus placebo.
Across the pooled analysis, the panel reported a relative risk for hospitalization of 0.19 and a relative risk for clinical worsening of 0.28, favoring sotatercept.
Sotatercept is dosed subcutaneously with a starting dose of 0.3 mg/kg and a target dose of 0.7 mg/kg. Pharmacists can help educate patients on administration, storage, and adhering to the follow-up schedule.
Increased hemoglobin and thrombocytopenia are the most common hematologic adverse events associated with sotatercept. The guideline notes that these may require treatment interruption or dose modification.
Bleeding events were reported in 21.5% of patients on sotatercept versus 12.5% on placebo. Severe bleeding occurred in 5.2% of patients and was associated with concomitant oral anticoagulation in roughly half of cases.
A key point for pharmacists is to monitor the anticoagulation gap and surface anticoagulant use during medication reconciliation. Counseling should prime patients to report nosebleeds, unusual bruising, or bleeding that does not stop.
The update also addresses right heart catheterization (RHC) during follow-up, conditionally suggesting it for patients at intermediate-low, intermediate-high, or high risk when a therapeutic consequence is expected.
Because sotatercept’s long-term effects on the right ventricle remain incompletely understood, the guideline stresses that patients be followed in specialized PH centers and that all potentially related adverse events be reported in line with good pharmacovigilance practice.
