Time-Dependent Risk of Cardiovascular Events Following an Exacerbation in Patients With Chronic Obstructive Pulmonary Disease: Post Hoc Analysis From the IMPACT Trial

Mark T. Dransfield*, Gerard J. Criner, David M.G. Halpin, Meilan K. Han, Benjamin Hartley, Ravi Kalhan, Peter Lange, David A. Lipson, Fernando J. Martinez, Dawn Midwinter, Dave Singh, Robert Wise, Ken M. Kunisaki

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

BACKGROUND: The association between chronic obstructive pulmonary disease exacerbations and increased cardiovascular event risk has not been adequately studied in a heterogenous population with both low and high cardiovascular risk. METHODS AND RESULTS: This post hoc analysis of the IMPACT (Informing the Pathway of COPD Treatment) trial (N=10 355 symptomatic patients with chronic obstructive pulmonary disease at risk of exacerbations) evaluated time-dependent risk of cardiovascular adverse events of special interest (CVAESI) following exacerbations and impact of exacerbation history, cardiovascular risk factors, and study treatment on this association. Risk (time-to-first) of CVAESI or CVAESI resulting in hospitalization or death was assessed during and 1 to 30, 31 to 90, and 91 to 365 days after resolution of moderate or severe exacerbations. CVAESI risk was compared between the period before and during/after exacerbation. CVAESI risk increased significantly during a moderate (hazard ratio [HR], 2.63 [95% CI, 2.08– 3.32]) or severe (HR, 21.84 [95% CI, 17.71– 26.93]) exacerbation and remained elevated for 30 days following an exacerbation (moderate: HR, 1.63 [95% CI, 1.28– 2.08]; severe: HR, 1.75 [95% CI, 0.99– 3.11; nonsignificant]) and decreased over time, returning to baseline by 90 days. Risk of CVAESI resulting in hospitalization or death also increased during an exacerbation (moderate: HR, 2.46 [95% CI, 1.53– 3.97]; severe: HR, 41.29 [95% CI, 30.43– 56.03]) and decreased in a similar time-dependent pattern. Results were consistent regardless of exacerbation history, cardiovascular risk at screening, or study treatment. CONCLUSIONS: Overall risk of cardiovascular events was higher during and in the 30 days following chronic obstructive pulmonary disease exacerbations, even among those with low cardiovascular risk, highlighting the need for exacerbation prevention and vigilance for cardiovascular events following exacerbations. REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT02164513; Unique identifier: NCT02164513.

Original languageEnglish (US)
Article numbere024350
JournalJournal of the American Heart Association
Volume11
Issue number18
DOIs
StatePublished - Sep 20 2022

Funding

Other Contributions: Editorial support (in the form of writing assistance, including preparation of the initial draft under the direction and guidance of the authors, collating and incorporating authors’ comments for each draft, assembling tables and figures, grammatical editing and referencing) was provided by Ellen Barker, PhD, and Alexandra Berry, PhD, at Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GlaxoSmithKline. This study was funded by GSK (study number CTT116855; NCT02164513). The funders of the study had a role in the study design, data analysis, data interpretation, and writing of the report. The corresponding author had full access to all the data and the final responsibility to submit for publication. Ellipta is owned by or licensed to the GSK group of companies. Dave Singh is supported by the National Institute for Health Research Manchester Biomedical Research Centre.

Keywords

  • LAMA/LABA
  • cardiovascular disease
  • chronic obstructive pulmonary disease
  • exacerbations
  • triple therapy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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