Journal Article Meta-Analysis Ppublish
PubMed: 40772955 DOI: 10.1164/rccm.202412-2371OC
Hemodynamics and Phosphodiesterase-5 Inhibitor Treatment Associated with Survival in Pulmonary Hypertension in Interstitial Lung Disease: A PVRI GoDeep Meta-Registry Analysis.
Am J Respir Crit Care Med 211(10):1855-1866
Authors: Athiththan Yogeswaran, Paul M Hassoun, Khaled Saleh, Meike Fünderich, Aparna Balasubramanian, Ziad Konswa, David G Kiely, Allen Lawrie, Thenappan Thenappan, Christina A Eichstaedt, Ekkehard Grünig, Martin R Wilkins, Luke Howard, Horst Olschewski, Gabor Kovacs, Hector R Cajigas, Robert Frantz, Hani Sabbour, Andrew J Sweatt, Roham T Zamanian, Alexandra Arvanitaki, George Giannakoulas, Jean Elwing, Arun Jose, Stephan Beckmann, Karen M Olsson, Stefan Stadler, Matthias Held, Michael Halank, Ralf Ewert, Jürgen Behr, Katrin Milger-Kneidinger, Christine Pausch, David Pittrow, Raphael W Majeed, Jochen Wilhelm, Hossein Ardeschir Ghofrani, Friedrich Grimminger, Khodr Tello, Marius M Hoeper, Werner Seeger
Affiliations
- Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany.
- Institute for Lung Health, Cardio-Pulmonary Institute, Giessen, Germany.
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
- Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, University of Sheffield and National Institute for Health and Care Research Sheffield Biomedical Research Centre, Sheffield, United Kingdom.
- National Heart and Lung Institute, Imperial College London, London, United Kingdom.
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
- German Center for Lung Research, Center for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital and Translational Lung Research Center Heidelberg, Heidelberg, Germany.
- Laboratory for Molecular Genetic Diagnostics, Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
- University Hospital Graz, Graz, Austria.
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota.
- Division of Pulmonary, Allergy, and Critical Care and Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University, Stanford, California.
- 1st Department of Cardiology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
- University of Cincinnati, Cincinnati, Ohio.
- Pulmonary and Critical Care Medicine Department, Loewenstein Lung Center, Germany.
- Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
- Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany.
- Department of Internal Medicine, Respiratory Medicine and Ventilatory Support, Medical Mission Hospital, Central Clinic Würzburg, Würzburg, Germany.
- Division of Pulmonology, Medical Department I, University Hospital Carl Gustav Carus of Technical University Dresden, Dresden, Germany.
- Clinic of Internal Medicine, Department of Respiratory Medicine, Universitätsmedizin Greifswald, Greifswald, Germany.
- Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich, Member of the German Center for Lung Research, Munich, Germany.
- Innovation Center Real-World Evidence, GWT-TUD GmbH, Dresden, Germany.
- Institute for Clinical Pharmacology, Medical Faculty, Technical University Dresden, Dresden, Germany; and.
- Institute of Medical Informatics, RWTH Aachen University, Aachen, Germany.
Abstract
Rationale: Pulmonary hypertension (PH) in interstitial lung disease (ILD) lacks approved therapies. Objectives: The Pulmonary Vascular Research Institute GoDeep metaregistry collects real-world data of patients with PH from international PH referral centers. Methods: Patients with ILD-PH and relevant subgroups (idiopathic interstitial pneumonia [IIP], idiopathic pulmonary fibrosis [IPF]) were stratified by pulmonary vascular resistance (PVR). Kaplan-Meier survival analyses and adjusted Cox proportional hazards models were employed, additionally accounting for immortal time bias, sensitivity analyses, Heller explained relative risk statistics, and target trial emulation framework analysis. Measurements and Main Results: Among 34,482 patients, 940 with hemodynamically fully characterized incident ILD-PH (median age, 67 [IQR, 59-74] yr) were identified. A total of 62% had severe ILD-PH with PVR >5 Wood units (WU) and poor survival rates (29% and 18% at 3 and 5 yr), significantly worse than patients with ILD-PH with PVR ⩽5 WU and patients with pulmonary arterial hypertension. Survival was poorest in severe IPF-PH. A total of 59% of all patients ILD-PH received PH-targeted therapy, predominantly phosphodiesterase-5 inhibitors (PDE5is). PDE5i treatment was consistently associated with significantly improved survival in patients with severe PH (hazard ratios of 0.537 [0.370-0.781], 0.461 [0.233-0.913], and 0.435 [0.215-0.8] for IIP-PH, IPF-PH, and IIP-PH with nintedanib/pirfenidone background therapy), but not in patients with less severe hemodynamic impairment, supported by sensitivity analyses, Heller statistics, and target trial emulation framework analysis. The survival statistics of patients with PDE5i-treated IIP-PH or IPF-PH were validated in the independent COMPERA registry. Combination therapy with PDE5is and inhaled prostacyclin analogues was superior to monotherapy using PDE5is (hazard ratio, 0.341; 0.205-0.566). Conclusions: Prognosis in ILD-PH was generally very poor and was related to PH severity. PDE5i treatment in severe IIP-PH and IPF-PH was associated with improved survival, which is to be further verified in controlled trials.
MeSH
Registries, Phosphodiesterase 5 Inhibitors, Hypertension, Pulmonary, Phosphoric Diester Hydrolases, Critical Care, Cyclic Nucleotide Phosphodiesterases, Type 5, Therapeutics, Hemodynamics, Lung Diseases, Interstitial