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Review
. 2024 Oct 31;64(4):2401325.
doi: 10.1183/13993003.01325-2024. Print 2024 Oct.

Treatment algorithm for pulmonary arterial hypertension

Kelly M Chin  1 , Sean P Gaine  2 , Christian Gerges  3 , Zhi-Cheng Jing  4 , Stephen C Mathai  5 , Yuichi Tamura  6 , Vallerie V McLaughlin  7   8 , Olivier Sitbon  9   10
Affiliations
Review

Treatment algorithm for pulmonary arterial hypertension

Kelly M Chin et al. Eur Respir J. .

Abstract

Pulmonary arterial hypertension leads to significant impairment in haemodynamics, right heart function, exercise capacity, quality of life and survival. Current therapies have mechanisms of action involving signalling via one of four pathways: endothelin-1, nitric oxide, prostacyclin and bone morphogenetic protein/activin signalling. Efficacy has generally been greater with therapeutic combinations and with parenteral therapy compared with monotherapy or nonparenteral therapies, and maximal medical therapy is now four-drug therapy. Lung transplantation remains an option for selected patients with an inadequate response to therapies.

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Conflict of interest statement

Conflict of interest: K.M. Chin reports grants and consultancy fees from Janssen, Merck, Gossamer Bio and United Therapeutics, support for attending meetings from Janssen, and is an associate editor for Circulation. S.P. Gaine reports grants from Janssen, Aerovent and Gossamer Bio, consultancy fees from Janssen, Merck, Gossamer Bio, United Therapeutics and Altavent, payment or honoraria for lectures, presentations, manuscript writing or educational events and support for attending meetings from Janssen, and participation on a data safety monitoring board or advisory board with Janssen. C. Gerges reports grants from OrphaCare, payment or honoraria for lectures, presentations, manuscript writing or educational events from AOPHealth, AstraZeneca, Janssen and Ferrer, and support for attending meetings from AOPHealth, AstraZeneca, Cordis, Janssen and MSD. Z-C. Jing has no potential conflicts of interest to disclose. S.C. Mathai reports consultancy fees from Janssen, United Therapeutics, Merck and Acceleron, participation on a data safety monitoring board or advisory board with Bayer, and a leadership role on the Patient Centered Outcomes Research Institute Rare Disease Advisory Panel. Y. Tamura reports grants from Nippon Shinyaku Co. Ltd and Mochida, consultancy fees from MSD, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Nippon Shinyaku Co. Ltd and Janssen Pharmaceuticals. V.V. McLaughlin reports grants from Aerovate, Gossamer-Bio, Janssen, Keros, Merck and Sonovie, and consultancy fees from 35Pharma, Aerami, Aerovate, Caremark, L.L.C., Corvista, Gossamer Bio, Janssen, Keros, Merck, Riovant and United Therapeutics. O. Sitbon reports grants from Aerovate, AOP Orphan, Ferrer, Janssen and MSD, consultancy fees from Altavant/Enzyvant, AOP Orphan, Ferrer, Gossamer Bio, Janssen, Liquidia, MSD, Respira Therapeutics and Roivant Sciences, payment or honoraria for lectures, presentations, manuscript writing or educational events from Aerovate, AOP Orphan, Janssen, Ferrer and MSD, and participation on a data safety monitoring board or advisory board with Altavant/Enzyvant, Gossamer Bio, Janssen and Respira Therapeutics.

Figures

FIGURE 1
FIGURE 1
Treatment algorithm. PAH: pulmonary arterial hypertension; IPAH: idiopathic PAH; HPAH: hereditary PAH; DT: drug and toxin; CTD: connective tissue disease; ERA: endothelin-1 receptor antagonist; PDE-5i: phosphodiesterase-5 inhibitor; i.v.: intravenous; s.c.: subcutaneous; PPA: prostacyclin pathway agent; sGCS: soluble guanylyl cyclase stimulator; Rx: prescription; mPAP: mean pulmonary artery pressure; PVR: pulmonary vascular resistance; FC: functional class; 6MWD: 6-min walk distance; RV: right ventricle.
FIGURE 2
FIGURE 2
Pulmonary arterial hypertension (PAH) therapies work through four major pathways: endothelin-1 receptor antagonists (ERAs) block the endothelin (ET)-1 receptor. Phosphodiesterase-5 inhibitors (PDE-5i) and soluble guanylyl cyclase (sGC) stimulators increase signalling in the nitric oxide (NO) and cyclic GMP (cGMP) pathway, resulting in increased cGMP levels, and prostacyclin (PGI2) and other prostacyclin pathway agents (PPAs) bind the prostacyclin receptor (IP receptor), promoting the production of cAMP, leading to vasodilation and inhibiting vascular cell growth. Sotatercept, a novel biologic agent targeting the transforming growth factor-β superfamily, acts as a ligand trap for activins and related growth factors. This helps rebalance growth-promoting and growth-inhibiting signalling pathways, with multiple downstream effects. Signalling is shown as proceeding from endothelial cell to smooth muscle cell for simplicity, but is bidirectional. BMPR: bone morphogenetic protein receptor; ALK: anaplastic lymphocyte kinase; ActR: activin receptor. #: in addition, signalling mediators also originate from multiple other cell types, particularly for activin.
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Comment in

References

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