Prognostic value of improvement endpoints in pulmonary arterial hypertension trials: A COMPERA analysis.

Biomarkers Familial Primary Pulmonary Hypertension Humans Hypertension, Pulmonary Natriuretic Peptide, Brain Peptide Fragments Prognosis Pulmonary Arterial Hypertension Treatment Outcome
clinical trials endpoints mortality pulmonary arterial hypertension risk treatment

Journal

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
ISSN: 1557-3117
Titre abrégé: J Heart Lung Transplant
Pays: United States
ID NLM: 9102703

Informations de publication

Date de publication:
07 2022
Historique:
received: 19 01 2022
revised: 23 02 2022
accepted: 10 03 2022
pubmed: 18 4 2022
medline: 30 6 2022
entrez: 17 4 2022
Statut: ppublish

Résumé

The prognostic value of improvement endpoints that have been used in clinical trials of treatments for pulmonary arterial hypertension (PAH) needs to be further investigated. Using the COMPERA database, we evaluated the prognostic value of improvements in functional class (FC) and absolute or relative improvements in 6-min walking distance (6MWD) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). In addition, we investigated multicomponent endpoints based on prespecified improvements in FC, 6MWD and NT-proBNP that have been used in recent PAH trials. Finally, we assessed the predictive value of improvements determined by risk stratification tools. The effects of changes from baseline to first follow-up (3-12 months after initiation of PAH therapy) on consecutive survival were determined by Kaplan-Meier analysis with Log-Rank testing and Cox proportional hazard analyses. All analyses were based on 596 patients with newly diagnosed PAH for whom complete data were available at baseline and first follow-up. Improvements in FC were associated with improved survival, whereas absolute or relative improvements in 6MWD had no predictive value. For NT-proBNP, absolute declines conferred no prognostic information while relative declines by ≥35% were associated with better survival. Improvements in multicomponent endpoints were associated with improved survival and the same was found for risk stratification tools. While sole improvements in 6MWD and NT-proBNP had minor prognostic relevance, improvements in multicomponent endpoints and risk stratification tools based on FC, 6MWD, and NT-proBNP were associated with improved survival. These tools should be further explored as outcome measures in PAH trials.

Sections du résumé

BACKGROUND
The prognostic value of improvement endpoints that have been used in clinical trials of treatments for pulmonary arterial hypertension (PAH) needs to be further investigated.
METHODS
Using the COMPERA database, we evaluated the prognostic value of improvements in functional class (FC) and absolute or relative improvements in 6-min walking distance (6MWD) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). In addition, we investigated multicomponent endpoints based on prespecified improvements in FC, 6MWD and NT-proBNP that have been used in recent PAH trials. Finally, we assessed the predictive value of improvements determined by risk stratification tools. The effects of changes from baseline to first follow-up (3-12 months after initiation of PAH therapy) on consecutive survival were determined by Kaplan-Meier analysis with Log-Rank testing and Cox proportional hazard analyses.
RESULTS
All analyses were based on 596 patients with newly diagnosed PAH for whom complete data were available at baseline and first follow-up. Improvements in FC were associated with improved survival, whereas absolute or relative improvements in 6MWD had no predictive value. For NT-proBNP, absolute declines conferred no prognostic information while relative declines by ≥35% were associated with better survival. Improvements in multicomponent endpoints were associated with improved survival and the same was found for risk stratification tools.
CONCLUSION
While sole improvements in 6MWD and NT-proBNP had minor prognostic relevance, improvements in multicomponent endpoints and risk stratification tools based on FC, 6MWD, and NT-proBNP were associated with improved survival. These tools should be further explored as outcome measures in PAH trials.

Identifiants

DOI: 10.1016/j.healun.2022.03.011 PMID: 35430147
pubmed: 35430147
pii: S1053-2498(22)01856-3
doi: 10.1016/j.healun.2022.03.011
pii:
doi:

Substances chimiques

Biomarkers 0
Peptide Fragments 0
Natriuretic Peptide, Brain 114471-18-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

971-981

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Marius M Hoeper (MM)

Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; German Center of Lung Research (DZL), Germany. Electronic address: hoeper.marius@mh-hannover.de.

Christine Pausch (C)

GWT-TUD GmbH, Epidemiological Centre, Dresden, Germany.

Karen M Olsson (KM)

Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; German Center of Lung Research (DZL), Germany.

Doerte Huscher (D)

Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany.

David Pittrow (D)

GWT-TUD GmbH, Epidemiological Centre, Dresden, Germany; Institute for Clinical Pharmacology, Medical Faculty, Technical University, Dresden, Germany.

Ekkehard Grünig (E)

Center for Pulmonary Hypertension, Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany.

Gerd Staehler (G)

Lungenklinik, Löwenstein, Germany.

Carmine Dario Vizza (CD)

Dipartimento di Scienze Cliniche Internistiche, Anestiologiche e Cardiolohiche, Sapienza, University of Rome, Rome, Italy.

Henning Gall (H)

German Center of Lung Research (DZL), Germany; Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany.

Oliver Distler (O)

Department of Rheumatology, University Hospital, Zurich, Switzerland.

Christian Opitz (C)

Department of Cardiology, DRK Kliniken Berlin Westend, Berlin, Germany.

J Simon R Gibbs (JSR)

Department of Cardiology, National Heart & Lung Institute, Imperial College London, United Kingdom.

Marion Delcroix (M)

Clinical Dept of Respiratory Diseases, University Hospitals of Leuven and Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Dept of Chronic Diseases and Metabolism (CHROMETA), KU Leuven - University of Leuven, Leuven, Belgium.

H Ardeschir Ghofrani (HA)

German Center of Lung Research (DZL), Germany; Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany; Department of Medicine, Imperial College London, London, United Kingdom.

Ralf Ewert (R)

Clinic of Internal Medicine, Department of Respiratory Medicine, Universitätsmedizin Greifswald, Germany.

Harald Kaemmerer (H)

Deutsches Herzzentrum München, Klinik für angeborene Herzfehler und Kinderkardiologie, TU München, Munich, Germany.

Hans-Joachim Kabitz (HJ)

Gemeinnützige Krankenhausbetriebsgesellschaft Konstanz mbH, Medizinische Klinik II, Konstanz, Germany.

Dirk Skowasch (D)

Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik II, Innere Medizin - Kardiologie/Pneumologie, Bonn, Germany.

Juergen Behr (J)

Comprehensive Pneumology Center, Lungenforschungsambulanz, Helmholtz Zentrum, München, Germany; Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.

Katrin Milger (K)

Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.

Michael Halank (M)

Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden, Medizinische Klinik und Poliklinik I, Dresden, Germany.

Heinrike Wilkens (H)

Klinik für Innere Medizin V, Pneumologie, Universitätsklinikum Universitätsklinikum des Saarlandes, Homburg, Germany.

Hans-Jürgen Seyfarth (HJ)

Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik II, Abteilung für Pneumologie, Leipzig, Germany.

Matthias Held (M)

Department of Internal Medicine, Respiratory Medicine and Ventilatory Support, Medical Mission Hospital, Central Clinic Würzburg, Germany.

Daniel Dumitrescu (D)

Clinic for General and Interventional Cardiology and Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany.

Iraklis Tsangaris (I)

Attikon University Hospital, 2nd Critical Care Department, National and Kapodistrian University of Athens, Athens, Greece.

Anton Vonk-Noordegraaf (A)

Amsterdam UMC, Vrije Universiteit Amsterdam, dept of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands.

Silvia Ulrich (S)

Clinic of Pulmonology, University Hospital of Zurich, Zurich, Switzerland.

Hans Klose (H)

Department of Respiratory Medicine, Eppendorf University Hospital, Hamburg, Germany.

Martin Claussen (M)

LungenClinic Grosshansdorf, Fachabteilung Pneumologie, Großhansdorf, Germany.

Stephan Eisenmann (S)

Universitätsklinikum Halle, Department of Respiratory Medicine, Halle, Germany.

Kai-Helge Schmidt (KH)

Department of Cardiology and Center of Thrombosis and Hemostasis (CTH); University Medical Center Mainz, Germany.

Stephan Rosenkranz (S)

Clinic III for Internal Medicine (Cardiology) and Center for Molecular Medicine (CMMC), and the Cologne Cardiovascular Research Center (CCRC), University of Cologne, Germany.

Tobias J Lange (TJ)

University Medical Center Regensburg, Department of Internal Medicine II, Regensburg, Germany.

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Prognostic value of improvement endpoints in...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Maladies pulmonaires › Hypertension artérielle pulmonaire primitive familiale › Prognostic value of improvement endpoints in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Prognostic value of improvement endpoints in...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Hypertension artérielle › Hypertension pulmonaire › Prognostic value of improvement endpoints in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Peptide natriurétique cérébral › Prognostic value of improvement endpoints in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Fragments peptidiques › Prognostic value of improvement endpoints in...
questionsmedicales.fr › Diagnostic › Pronostic › Prognostic value of improvement endpoints in...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Maladies pulmonaires › Hypertension artérielle pulmonaire › Prognostic value of improvement endpoints in...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Prognostic value of improvement endpoints in...