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The Impact of Exacerbation History on the Safety and Efficacy of Aclidinium in Patients with Chronic Obstructive Pulmonary Disease and Increased Cardiovascular Risk: ASCENT-COPD Trial
PURPOSE: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased risk of major adverse cardiovascular events (MACE) and mortality. Here, we investigate whether the safety and efficacy of aclidinium bromide differ due to exacerbation history in patients with COPD and...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987267/ https://www.ncbi.nlm.nih.gov/pubmed/33776428 http://dx.doi.org/10.2147/COPD.S285068 |
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author | Wise, Robert A Chapman, Kenneth R Scirica, Benjamin M Daoud, Sami Z Lythgoe, Dan Garcia-Gil, Esther |
author_facet | Wise, Robert A Chapman, Kenneth R Scirica, Benjamin M Daoud, Sami Z Lythgoe, Dan Garcia-Gil, Esther |
author_sort | Wise, Robert A |
collection | PubMed |
description | PURPOSE: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased risk of major adverse cardiovascular events (MACE) and mortality. Here, we investigate whether the safety and efficacy of aclidinium bromide differ due to exacerbation history in patients with COPD and increased cardiovascular risk. PATIENTS AND METHODS: ASCENT-COPD was a Phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group study of patients with moderate-to-very severe COPD and increased cardiovascular risk. Patients were randomized 1:1 to receive aclidinium or placebo twice daily for up to 3 years. Outcomes included time to first MACE and all-cause mortality over 3 years, exacerbation rate during the first year on-treatment, and change in baseline pre-dose forced expiratory volume in 1 second (FEV(1)) over 3 years. This pre-specified subgroup analysis compared outcomes in patients receiving aclidinium vs placebo. The comparison of patients with vs without an exacerbation history was added following a protocol amendment to increase enrollment in the primary study. RESULTS: Of 3589 patients, 2156 (60.1%) had ≥1 moderate or severe exacerbations in the prior year, compared with 1433 (39.9%) without prior exacerbations. Although patients with an exacerbation history had numerically higher rates of MACE and mortality regardless of treatment, aclidinium did not increase risk of MACE (≥1: hazard ratio [HR] 0.79, 95% confidence interval [CI]: 0.54–1.16; none: HR 1.27, 95% CI: 0.65–2.47; interaction P=0.233) or all-cause mortality (≥1: HR 1.08, 95% CI: 0.81–1.43; none: HR 0.66, 95% CI: 0.36–1.22; interaction P=0.154), regardless of exacerbation history. Aclidinium reduced the exacerbation rate vs placebo irrespective of exacerbation history (≥1: rate ratio [RR] 0.80, 95% CI: 0.68–0.94; none: RR 0.69, 95% CI: 0.54–0.89; interaction P=0.340) and improved FEV(1) (interaction P=0.633). CONCLUSION: In patients with moderate-to-very severe COPD and increased cardiovascular risk, aclidinium did not increase risk of MACE or mortality and reduced exacerbation rate vs placebo, regardless of exacerbation history. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01966107. |
format | Online Article Text |
id | pubmed-7987267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-79872672021-03-25 The Impact of Exacerbation History on the Safety and Efficacy of Aclidinium in Patients with Chronic Obstructive Pulmonary Disease and Increased Cardiovascular Risk: ASCENT-COPD Trial Wise, Robert A Chapman, Kenneth R Scirica, Benjamin M Daoud, Sami Z Lythgoe, Dan Garcia-Gil, Esther Int J Chron Obstruct Pulmon Dis Original Research PURPOSE: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased risk of major adverse cardiovascular events (MACE) and mortality. Here, we investigate whether the safety and efficacy of aclidinium bromide differ due to exacerbation history in patients with COPD and increased cardiovascular risk. PATIENTS AND METHODS: ASCENT-COPD was a Phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group study of patients with moderate-to-very severe COPD and increased cardiovascular risk. Patients were randomized 1:1 to receive aclidinium or placebo twice daily for up to 3 years. Outcomes included time to first MACE and all-cause mortality over 3 years, exacerbation rate during the first year on-treatment, and change in baseline pre-dose forced expiratory volume in 1 second (FEV(1)) over 3 years. This pre-specified subgroup analysis compared outcomes in patients receiving aclidinium vs placebo. The comparison of patients with vs without an exacerbation history was added following a protocol amendment to increase enrollment in the primary study. RESULTS: Of 3589 patients, 2156 (60.1%) had ≥1 moderate or severe exacerbations in the prior year, compared with 1433 (39.9%) without prior exacerbations. Although patients with an exacerbation history had numerically higher rates of MACE and mortality regardless of treatment, aclidinium did not increase risk of MACE (≥1: hazard ratio [HR] 0.79, 95% confidence interval [CI]: 0.54–1.16; none: HR 1.27, 95% CI: 0.65–2.47; interaction P=0.233) or all-cause mortality (≥1: HR 1.08, 95% CI: 0.81–1.43; none: HR 0.66, 95% CI: 0.36–1.22; interaction P=0.154), regardless of exacerbation history. Aclidinium reduced the exacerbation rate vs placebo irrespective of exacerbation history (≥1: rate ratio [RR] 0.80, 95% CI: 0.68–0.94; none: RR 0.69, 95% CI: 0.54–0.89; interaction P=0.340) and improved FEV(1) (interaction P=0.633). CONCLUSION: In patients with moderate-to-very severe COPD and increased cardiovascular risk, aclidinium did not increase risk of MACE or mortality and reduced exacerbation rate vs placebo, regardless of exacerbation history. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01966107. Dove 2021-03-18 /pmc/articles/PMC7987267/ /pubmed/33776428 http://dx.doi.org/10.2147/COPD.S285068 Text en © 2021 Wise et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Wise, Robert A Chapman, Kenneth R Scirica, Benjamin M Daoud, Sami Z Lythgoe, Dan Garcia-Gil, Esther The Impact of Exacerbation History on the Safety and Efficacy of Aclidinium in Patients with Chronic Obstructive Pulmonary Disease and Increased Cardiovascular Risk: ASCENT-COPD Trial |
title | The Impact of Exacerbation History on the Safety and Efficacy of Aclidinium in Patients with Chronic Obstructive Pulmonary Disease and Increased Cardiovascular Risk: ASCENT-COPD Trial |
title_full | The Impact of Exacerbation History on the Safety and Efficacy of Aclidinium in Patients with Chronic Obstructive Pulmonary Disease and Increased Cardiovascular Risk: ASCENT-COPD Trial |
title_fullStr | The Impact of Exacerbation History on the Safety and Efficacy of Aclidinium in Patients with Chronic Obstructive Pulmonary Disease and Increased Cardiovascular Risk: ASCENT-COPD Trial |
title_full_unstemmed | The Impact of Exacerbation History on the Safety and Efficacy of Aclidinium in Patients with Chronic Obstructive Pulmonary Disease and Increased Cardiovascular Risk: ASCENT-COPD Trial |
title_short | The Impact of Exacerbation History on the Safety and Efficacy of Aclidinium in Patients with Chronic Obstructive Pulmonary Disease and Increased Cardiovascular Risk: ASCENT-COPD Trial |
title_sort | impact of exacerbation history on the safety and efficacy of aclidinium in patients with chronic obstructive pulmonary disease and increased cardiovascular risk: ascent-copd trial |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987267/ https://www.ncbi.nlm.nih.gov/pubmed/33776428 http://dx.doi.org/10.2147/COPD.S285068 |
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