Renin–angiotensin–system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study

Objective The renin–angiotensin system (RAS) has been shown to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD) because of the inflammatory properties of the system. Many patients with COPD use RAS-inhibiting (RASi) treatment. The aim was to determine the association b...

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Main Authors: Pradeesh Sivapalan, Rikke Sørensen, Josefin Eklöf, Jens-Ulrik Stæhr Jensen, Tor Biering-Sørensen, Lars Pedersen, Ole Hilberg, Tobias Wirenfeldt Klausen, Caroline Hedsund, Frida Vilstrup, Christian Kjer Heerfordt, Peter Kamstrup, Shailesh Kolekar, Thomas Kromann Lund, Kristoffer Grundtvig Skaarup
Format: Article
Language:English
Published: BMJ Publishing Group 2023-07-01
Series:BMJ Open Respiratory Research
Online Access:https://bmjopenrespres.bmj.com/content/10/1/e001428.full
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author Pradeesh Sivapalan
Rikke Sørensen
Josefin Eklöf
Jens-Ulrik Stæhr Jensen
Tor Biering-Sørensen
Lars Pedersen
Ole Hilberg
Tobias Wirenfeldt Klausen
Caroline Hedsund
Frida Vilstrup
Christian Kjer Heerfordt
Peter Kamstrup
Shailesh Kolekar
Thomas Kromann Lund
Kristoffer Grundtvig Skaarup
author_facet Pradeesh Sivapalan
Rikke Sørensen
Josefin Eklöf
Jens-Ulrik Stæhr Jensen
Tor Biering-Sørensen
Lars Pedersen
Ole Hilberg
Tobias Wirenfeldt Klausen
Caroline Hedsund
Frida Vilstrup
Christian Kjer Heerfordt
Peter Kamstrup
Shailesh Kolekar
Thomas Kromann Lund
Kristoffer Grundtvig Skaarup
author_sort Pradeesh Sivapalan
collection DOAJ
description Objective The renin–angiotensin system (RAS) has been shown to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD) because of the inflammatory properties of the system. Many patients with COPD use RAS-inhibiting (RASi) treatment. The aim was to determine the association between treatment with RASi and the risk of acute exacerbations and mortality in patients with severe COPD.Methods Active comparator analysis by propensity-score matching. Data were collected in Danish national registries, containing complete information on health data, prescriptions, hospital admissions and outpatient clinic visits. Patients with COPD (n=38 862) were matched by propensity score on known predictors of the outcome. One group was exposed to RASi treatment (cases) and the other was exposed to bendroflumethiazide as an active comparator in the primary analysis.Results The use of RASi was associated with a reduced risk of exacerbations or death in the active comparator analysis at 12 months follow-up (HR 0.86, 95% CI 0.78 to 0.95). Similar results were evident in a sensitivity analysis of the propensity-score-matched population (HR 0.89, 95% CI 0.83 to 0.94) and in an adjusted Cox proportional hazards model (HR 0.93, 95% CI 0.89 to 0.98).Conclusion In the current study, we found that the use of RASi treatment was associated with a consistently lower risk of acute exacerbations and death in patients with COPD. Explanations to these findings include real effect, uncontrolled biases, and—less likely—chance findings.
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spelling doaj-art-efaaf62f21ca43ac9546ebe5b31e3cde2025-08-20T02:59:45ZengBMJ Publishing GroupBMJ Open Respiratory Research2052-44392023-07-0110110.1136/bmjresp-2022-001428Renin–angiotensin–system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry studyPradeesh Sivapalan0Rikke Sørensen1Josefin Eklöf2Jens-Ulrik Stæhr Jensen3Tor Biering-Sørensen4Lars Pedersen5Ole Hilberg6Tobias Wirenfeldt Klausen7Caroline Hedsund8Frida Vilstrup9Christian Kjer Heerfordt10Peter Kamstrup11Shailesh Kolekar12Thomas Kromann Lund13Kristoffer Grundtvig Skaarup14Department of Internal Medicine, Zealand University Hospital, Roskilde, DenmarkDepartment of Cardiology, Copenhagen University Hospital, Kobenhavn, DenmarkSection of Respiratory Medicine, Department of Internal Medicine, Copenhagen University Hospital-Gentofte, Copenhagen, DenmarkDepartment of Clinical Medicine, University of Copenhagen Faculty of Health and Medical Sciences, Kobenhavn, DenmarkDepartment of Cardiology, Copenhagen University Hospital Herlev and Gentofte Hospital, Hellerup, Denmark2 Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Medicine, Sygehus Lillebalt Vejle Sygehus, Vejle, DenmarkDepartment of Medicine, Section of Respiratory Medicine, Herlev Hospital, Herlev, DenmarkDepartment of Medicine, Section of Respiratory Medicine, Gentofte University Hospital, Hellerup, DenmarkDepartment of Medicine, Section of Respiratory Medicine, Gentofte University Hospital, Hellerup, DenmarkSection of Respiratory Medicine, Department of Internal Medicine, Copenhagen University Hospital-Gentofte, Copenhagen, DenmarkSection of Respiratory Medicine, Department of Internal Medicine, Copenhagen University Hospital-Gentofte, Copenhagen, DenmarkDepartment of Clinical Medicine, University of Copenhagen, Kobenhavn, DenmarkSection for Lung Transplantation, Dept. of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, DenmarkDepartment of Cardiology, Copenhagen University Hospital Herlev and Gentofte Hospital, Hellerup, DenmarkObjective The renin–angiotensin system (RAS) has been shown to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD) because of the inflammatory properties of the system. Many patients with COPD use RAS-inhibiting (RASi) treatment. The aim was to determine the association between treatment with RASi and the risk of acute exacerbations and mortality in patients with severe COPD.Methods Active comparator analysis by propensity-score matching. Data were collected in Danish national registries, containing complete information on health data, prescriptions, hospital admissions and outpatient clinic visits. Patients with COPD (n=38 862) were matched by propensity score on known predictors of the outcome. One group was exposed to RASi treatment (cases) and the other was exposed to bendroflumethiazide as an active comparator in the primary analysis.Results The use of RASi was associated with a reduced risk of exacerbations or death in the active comparator analysis at 12 months follow-up (HR 0.86, 95% CI 0.78 to 0.95). Similar results were evident in a sensitivity analysis of the propensity-score-matched population (HR 0.89, 95% CI 0.83 to 0.94) and in an adjusted Cox proportional hazards model (HR 0.93, 95% CI 0.89 to 0.98).Conclusion In the current study, we found that the use of RASi treatment was associated with a consistently lower risk of acute exacerbations and death in patients with COPD. Explanations to these findings include real effect, uncontrolled biases, and—less likely—chance findings.https://bmjopenrespres.bmj.com/content/10/1/e001428.full
spellingShingle Pradeesh Sivapalan
Rikke Sørensen
Josefin Eklöf
Jens-Ulrik Stæhr Jensen
Tor Biering-Sørensen
Lars Pedersen
Ole Hilberg
Tobias Wirenfeldt Klausen
Caroline Hedsund
Frida Vilstrup
Christian Kjer Heerfordt
Peter Kamstrup
Shailesh Kolekar
Thomas Kromann Lund
Kristoffer Grundtvig Skaarup
Renin–angiotensin–system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study
BMJ Open Respiratory Research
title Renin–angiotensin–system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study
title_full Renin–angiotensin–system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study
title_fullStr Renin–angiotensin–system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study
title_full_unstemmed Renin–angiotensin–system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study
title_short Renin–angiotensin–system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study
title_sort renin angiotensin system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease a nationwide registry study
url https://bmjopenrespres.bmj.com/content/10/1/e001428.full
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