• Khodr Tello, Athiththan Yogeswaran, Raphael W Majeed, David G Kiely, Allan Lawrie, Evan Brittain, Jeffrey S Annis, Horst Olschewski, Gabor Kovacs, Paul M Hassoun, Aparna Balasubramanian, Ziad Konswa, Andrew J Sweatt, Roham T Zamanian, Martin R Wilkins, Luke Howard, Alexandra Arvanitaki, George Giannakoulas, Hector R Cajigas, Robert Frantz, Paul G Williams, Marlize Frauendorf, Kurt Marquardt, Tobiah Antoine, Meike Fuenderich, Manuel Richter, Friedrich Grimminger, Hossein-Ardeschir Ghofrani, Jochen Wilhelm, Werner Seeger, and Pulmonary Vascular Research Institute GoDeep Consortium.
• Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany; Institute for Lung Health, Cardio-Pulmonary Institute (CPI), Giessen, Germany.
• Chest. 2024 Sep 7.

BackgroundPatients 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 QuestionIs PH-targeted therapy associated with improved transplant-free survival in patients with COPD and PH?Study Design And MethodsThis 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.ResultsAs 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 (59-73 years), FEV1 of 51% predicted (34%-69% predicted), mPAP of 35 mm Hg (28-44 mm Hg), PVR of 5 WU (4-8 WU), cardiac index of 2.5 L/min/m2 (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 (0.57-0.75) for the entire cohort of patients with COPD and PH and of 0.83 (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.InterpretationPatients 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.Copyright © 2024. Published by Elsevier Inc.

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