De-Escalation of Prostacyclin-Based Therapy in Patients Treated With Sotatercept

Sotatercept represents a mechanistically distinct advance in the treatment of pulmonary arterial hypertension (PAH), with the potential to favorably modify pulmonary vascular remodeling beyond the effects of other PAH-specific therapies. As sotatercept is incorporated into background combination therapy, clinicians increasingly encounter patients (particularly those receiving prostacyclin therapy) who exhibit sustained clinical improvement, raising questions about whether prostacyclin de-escalation can be safely considered. However, commonly used tools for risk stratification and disease monitoring, including functional class, 6-minute walk distance, biomarkers, and composite risk scores, often lack sufficient resolution to guide de-escalation decisions, especially in higher functioning patients. In this How I Do It article, we review emerging evidence supporting prostacyclin de-escalation in carefully selected patients treated with sotatercept, discuss safety considerations and patient selection, and highlight the limitations of conventional monitoring strategies. We describe the role of cardiopulmonary exercise testing as a complementary, stress-based assessment of cardiopulmonary reserve and right ventricular-to-pulmonary vascular coupling, and propose a structured, decision-support framework integrating cardiopulmonary exercise testing alongside established clinical assessments. Using a representative clinical case, we illustrate how this approach may help reduce uncertainty and support individualized, shared decision-making when considering prostacyclin de-escalation in the sotatercept era.