Post by Wilfried Dinh, MD, MBA, FESC

🔬 State-of-the-art review, not new trial data. Synthesizes four decades of PAH science. Bottom line: PAH shifted from vasodilation to antiremodeling. Sotatercept, an activin ligand trap targeting the TGF-β pathway, is the first approved antiremodeling drug. 🧪 Mechanism landscape: Prostacyclin, endothelin, NO-cGMP: vasodilators, symptom control Activin/TGF-β (sotatercept): antiremodeling RTK/PDGF (seralutinib, imatinib): antiproliferative, mixed results 📊 Trial signals: STELLAR: +40.8 m 6MWD (surrogate) ZENITH: 76% risk reduction, hard composite (HR 0.24), stopped early Sotatercept cut death, transplant, or hospitalization by 76% in high-risk PA PROSERA (seralutinib): missed, +13.3 m nonsignificant 📈 ZENITH's outcome win is real, but sotatercept carries bleeding, telangiectasia, and pericardial-effusion signals needing long-term surveillance. Named COI: authors report ties to Merck (sotatercept), Janssen, AstraZeneca, Gossamer. Would antiremodeling change when you escalate therapy? Disclaimer: The views expressed are solely my own, made in my capacity as a private individual, MD, and researcher. They do not represent the positions of my employer or affiliates. For informational purposes only. https://lnkd.in/e7pjc6q6