A 40-year-old woman with diffuse cutaneous systemic sclerosis develops progressive exertional dyspnea, RHC shows mPAP 42 mmHg, PVR 5.2 Wood units, PCWP 10 mmHg, confirming Group 1 PAH. Her FVC is 72% predicted with DLCO 42%. Per EULAR and ACR guidelines, which treatment is most appropriate?

• A Oral endothelin receptor antagonist (ambrisentan) as monotherapy
• B Intravenous epoprostenol (prostacyclin)
• C Upfront oral combination therapy — endothelin receptor antagonist + PDE-5 inhibitor ✓
• D Immunosuppression with cyclophosphamide

Explanation

Current PAH guidelines (2022 ESC/ERS) recommend upfront combination oral therapy with an endothelin receptor antagonist plus PDE-5 inhibitor for treatment-naive Group 1 PAH in intermediate-risk patients. The AMBITION trial demonstrated superiority of ambrisentan + tadalafil over either monotherapy in PAH (40% reduction in clinical failure events). IV epoprostenol is reserved for high-risk or rapidly progressive disease. Cyclophosphamide targets ILD/skin fibrosis, not PAH. SSc-PAH carries the worst prognosis among connective tissue disease-associated PAH subtypes.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.