The Role of the Prostacyclin Pathway

EP: 1.Pathophysiology of Pulmonary Arterial Hypertension

EP: 2.Differential Diagnosis of Pulmonary Arterial Hypertension

EP: 3.Importance of Early Detection and Monitoring for Disease Progression

EP: 4.Risk Stratification and the Importance of Patient-Centered Care

EP: 5.Strengths and Limitations of Current Therapeutic Options

EP: 6.Overview of Different Therapies for Patients with Pulmonary Arterial Hypertension

EP: 7.Sotatercept for Patients with Pulmonary Arterial Hypertension

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EP: 8. The Role of the Prostacyclin Pathway

EP: 9.Important Clinical Considerations for Pulmonary Arterial Hypertension

EP: 10.Economic Impact of Pulmonary Arterial Hypertension

EP: 11.Barriers to Care for Patients with Pulmonary Arterial Hypertension

EP: 12.Utilizing Health Economic Outcomes in Clinical Practice

EP: 13.Outlining the Need for Equitable Access to Care

EP: 14.Final Panelist Thoughts on the Management of Pulmonary Arterial Hypertension

Paradigm Shift in PAH Management: Sotatercept vs. Prostacyclin Pathway Therapies

The introduction of sotatercept is driving a significant paradigm shift in pulmonary arterial hypertension (PAH) treatment, particularly regarding the role of prostacyclin pathway activators. While prostacyclin analogs have been the cornerstone of PAH therapy for over 20 years, regional differences exist in their utilization—European practitioners rely heavily on parenteral prostacyclins with fully implantable pumps, while prostacyclin receptor agonists are less commonly used compared to the United States. The superior efficacy evidence for sotatercept is already influencing clinical practice, with some centers beginning to prioritize sotatercept before prostacyclin therapy and exploring strategies to wean patients off prostacyclins after sotatercept initiation.

However, prostacyclin therapy retains crucial advantages in specific clinical scenarios, particularly for patients with severe right heart failure and low cardiac output states. While sotatercept demonstrates impressive reductions in pulmonary pressures and resistance, it notably does not significantly improve cardiac output—a key limitation when treating patients in low-flow states with overt right heart failure. For these critically ill patients, the proven 20-year track record of parenteral prostacyclins like epoprostenol and treprostinil remains invaluable, with many clinicians advocating for prostacyclin initiation followed by sotatercept addition to optimize treatment outcomes.

The real-world challenges of prostacyclin therapy continue to impact patient quality of life and treatment adherence, including significant side effects such as headaches, nausea, diarrhea, flushing, and jaw pain. Parenteral formulations require central venous catheters or subcutaneous pumps with continuous infusion, creating infection risks and daily management burdens including cassette changes and site pain. Despite sotatercept's promise and the paradigm shift it represents, prostacyclins serve as a "safety net" for experienced clinicians who value their extensive clinical experience with these agents. The future likely involves individualized treatment approaches combining both therapies, with timing and sequencing decisions based on patient risk profiles, hemodynamic status, and personal preferences while awaiting long-term safety data for sotatercept.