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. 2025 Jan;167(1):224-240.
doi: 10.1016/j.chest.2024.08.016. Epub 2024 Sep 7.

Association of Phosphodiesterase-5 Inhibitor Treatment With Improved Survival in Pulmonary Hypertension Associated With COPD in the Pulmonary Vascular Research Institute GoDeep Meta-Registry

Khodr Tello  1 , Athiththan Yogeswaran  1 , Raphael W Majeed  2 , David G Kiely  3 , Allan Lawrie  3 , Evan Brittain  4 , Jeffrey S Annis  4 , Horst Olschewski  5 , Gabor Kovacs  5 , Paul M Hassoun  6 , Aparna Balasubramanian  6 , Ziad Konswa  6 , Andrew J Sweatt  7 , Roham T Zamanian  7 , Martin R Wilkins  8 , Luke Howard  8 , Alexandra Arvanitaki  9 , George Giannakoulas  9 , Hector R Cajigas  10 , Robert Frantz  10 , Paul G Williams  11 , Marlize Frauendorf  11 , Kurt Marquardt  12 , Tobiah Antoine  12 , Meike Fuenderich  1 , Manuel Richter  12 , Friedrich Grimminger  1 , Hossein-Ardeschir Ghofrani  1 , Jochen Wilhelm  1 , Werner Seeger  13 ; Pulmonary Vascular Research Institute GoDeep Consortium
Affiliations

Association of Phosphodiesterase-5 Inhibitor Treatment With Improved Survival in Pulmonary Hypertension Associated With COPD in the Pulmonary Vascular Research Institute GoDeep Meta-Registry

Khodr Tello et al. Chest. 2025 Jan.

Abstract

Background: Patients with COPD frequently demonstrate pulmonary hypertension (PH). Severe PH in patients with COPD, identified by pulmonary vascular resistance (PVR) of > 5 Wood units (WU), is closely linked to impaired transplant-free survival. The impact of PH-targeting pharmacotherapy in this context remains unclear.

Research question: Is PH-targeted therapy associated with improved transplant-free survival in patients with COPD and PH?

Study design and methods: This study included Pulmonary Vascular Research Institute GoDeep meta-registry patients with COPD and PH and available right heart catheterization at diagnosis. We investigated PH-targeted therapy prevalence and its association with transplant-free survival using diverse statistical methods, including Cox regression and subgroup analyses based on PH severity, comorbidities, and pulmonary function test results. Immortal time bias was addressed through a landmark approach.

Results: As of December 2023, the GoDeep meta-registry included 26,981 patients (28% in PH group 1, 13% in PH group 2, 12% in PH group 3, 10% in PH group 4, 2% in PH group 5, 26% undefined, and 9% control participants). Of these, 836 patients had a diagnosis of COPD with PH and were included in this analysis, with median age of 66 years (interquartile range [IQR], 59-73 years), FEV1 of 51% predicted (IQR, 34%-69% predicted), mPAP of 35 mm Hg (IQR, 28-44 mm Hg), PVR of 5 WU (IQR, 4-8 WU), cardiac index of 2.5 L/min/m2 (IQR, 2.0-2.9 L/min/m2), and mostly World Health Organization functional class III were included. Five-year transplant-free survival was 42%, significantly worse than in group 1 PH. A multivariable Cox proportional hazards model identified PVR, but not FEV1, as a major predictor of outcome. Four hundred eighteen patients (50%) received phosphodiesterase-5 inhibitor (PDE5i) therapy, which was associated with significantly reduced mortality: hazard ratio of 0.65 (IQR, 0.57-0.75) for the entire cohort of patients with COPD and PH and of 0.83 (IQR, 0.74-0.94) when performing landmark analysis. This PDE5i effect was reproduced robustly when performing subgroup analyses for patients with moderate to severe PH, various comorbidities, and supplemental oxygen requirement and when assessing the impact of unobserved confounders.

Interpretation: Patients with COPD and PH exhibit poor transplant-free survival, with PVR being a predictor of mortality. In this meta-registry, PDE5i therapy was associated with a significant reduction in mortality across all tested models.

Keywords: COPD; meta-registry; phosphodiesterase 5 inhibitor therapy; pulmonary hypertension.

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Conflict of interest statement

Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: K. T. has received personal fees from Bayer, AstraZeneca, and Gossamer. A. Y. has received personal fees from MSD and support for scientific meetings from AOP. D. G. K. reports support from the Sheffield Biomedical Research Centre and consulting fees and other payments from Jansen Pharmaceuticals, Ferrer, Altavant, MSD, and United therapeutics. H. O. reports grants or contracts from Actelion, Bayer, Boehringer-Ingelheim, Janssen, MSD, IQVIA, and Pfizer; consulting fees from Bayer and IQVIA; speaker fees from Actelion, Bayer, Boehringer-Ingelheim, MSD, and Pfizer; support for scientific meetings from Astra Zeneca, Boehringer-Ingelheim, Menarini, and MSD; and participation on data safety board or advisory board for Bayer and IQVIA. G. K. reports consulting and speaker fees from Boehringer-Ingelheim, Janssen, MSD, Astra Zeneca, Chiesi, AOP, and Ferrer and support for scientific meetings from AOP, Vitalaire, MSD, and Boehringer-Ingelheim. P. M. H. reports personal fees from Merck Co. M. R. W. reports personal fees from MorphogenIX, Janssen, Chiesi, and Aerami; grants from British Heart Foundation and NIHR; and personal fees from MSD, Benevolent AI, and Tiakis Biotech outside the submitted work. L. H. reports personal fees and nonfinancial support from Janssen and personal fees from MSD, Gossamer, and Altavant. M. R. has received support from Janssen Pharmaceutica and Bayer Pharma AG, and speaker fees from Janssen Pharmaceutica and OMT. H.-A. G. has received fees from Actelion, AstraZeneca, Bayer, GSK, Janssen-Cilag, Lilly, Novartis, OMT, Pfizer, and United Therapeutics. W. S. has received consultancy fees from United Therapeutics, Tiakis Biotech AG, Liquidia, Pieris Pharmaceuticals, Abivax, Pfizer, and Medspray BV. None declared (R. W. M., A. L., E. B., J. S. A., A. B., Z. K., A. J. S., R. T. Z., A. A., G. G., H. R. C., R. F., P. G. W., M. Frauendorf, K. M., T. A., M. Feunerich, F. G., J. W.).

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