Pulmonary Arterial Hypertension-approved drugs in Pulmonary Hypertension associated with COPD: A systematic literature review
- PMID: 40318239
- DOI: 10.1016/j.resmer.2025.101165
Pulmonary Arterial Hypertension-approved drugs in Pulmonary Hypertension associated with COPD: A systematic literature review
Abstract
Introduction: Pulmonary hypertension (PH) is commonly associated with chronic obstructive pulmonary disease (COPD), with an estimated prevalence of 39%. PH reduces functional capacity and exercise tolerance, and increases the risk of COPD exacerbations and hospitalizations. PH associated with COPD (PH-COPD) typically manifests with moderate severity, progressing gradually in tandem with the level of bronchial obstruction. However, a specific subgroup with severe PH displays disproportionately high pulmonary vascular resistance, reduced diffusion capacity, and a severe prognosis.
Methods: This article is a systematic literature review of clinical trials including randomized controlled trials (RCTs), non-RCTs, cohort studies and registry data regarding PAH-approved drugs, in the context of PH-COPD, from January 2003 to January 2025.
Results: There have been three positive and three negative RCTs with phosphodiesterase-5 inhibitors, as well as one positive and one negative RCT with endothelin receptor antagonists. These RCTs suffered from limitations especially in severe PH cases. Additional data came from 16 studies, including non-RCTs, cohort studies and registry data, and the results were conflicting. The most robust study, a large phase 3 RCT using inhaled treprostinil, was terminated early due to an unfavorable benefit-risk ratio.
Conclusion: The evidence does not support PAH-approved drugs for mild-to-moderate PH-COPD, though potential benefits may exist for the severe PH subgroup. Large, multicenter RCTs are necessary to provide robust medical evidence and phase 2 and phase 3 clinical trials are ongoing. In the interim, suspected or confirmed severe PH-COPD should prompt referral to PH centers for personalized care and potential clinical trial participation.
Keywords: Chronic obstructive pulmonary disease; Pulmonary arterial hypertension-approved drugs; Pulmonary hypertension.
Copyright © 2025 SPLF and Elsevier Masson SAS. All rights reserved.
Conflict of interest statement
Declaration of competing interest Etienne-Marie Jutant reports consulting fees and payment for presentations from Chiesi Pharmaceuticals GMBH; payment for presentations from GSK, Merck Sharp & Dohme Corp, and Boehringer Ingelheim GmbH; travel support from Janssen Pharmaceuticals Inc; and non-financial support from the World Symposium on Pulmonary Hypertension Taskforce 2024. Elisa Larrieu Ardilouze reports payment for presentations from Merck Sharp & Dohme Corp and Bristol Myers Squibb Co. David Montani reports grants or contracts from Acceleron Pharma, Janssen Pharmaceuticals Inc, Merck Sharp & Dohme Corp; consulting fees from Janssen Pharmaceuticals Inc, Merck Sharp & Dohme Corp, and Ferrer; payment for presentations from Acceleron Pharma, Janssen Pharmaceuticals Inc, Merck Sharp & Dohme Corp, Ferrer, Bayer Schering Pharma AG, Chiesi Pharmaceuticals Inc, and GSK. He serves as Editor-in-Chief of Respiratory Medicine and Research. Xavier Jaïs reports grants or contracts from Acceleron, Janssen, MSD, Bayer Health Care; Consulting fees, payment for presentation and support for attending meeting from MSD. Lucilla Piccari reports grants or contracts from Ferrer; payment for presentations from Janssen, Ferrer, MSD, Medscape; support for attending meeting from Ferrer, MSD, Janssen, United Therapeutics, Gossamer Bio; participation on a data safety monitoring Board from Ferrer, Liquidia, Gossamer Bio. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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