Risk of Death and Cardiovascular Events Following an Exacerbation of COPD: The EXACOS-CV US Study

Abstract

Purpose

This study estimated the magnitude and duration of risk of cardiovascular events and mortality following acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and whether risks varied by number and severity of exacerbation in a commercially insured population in the United States.

Methods

This was a retrospective cohort study of newly diagnosed COPD patients ≥40 years old in the Healthcare Integrated Research Database from 2012 to 2019. Patients experiencing exacerbations comprised the “exacerbation cohort”. Moderate exacerbations were outpatient visits with contemporaneous antibiotic or glucocorticoid administration; severe exacerbations were emergency department visits or hospitalizations for AECOPD. Follow-up started on the exacerbation date. Distribution of time between diagnosis and first exacerbation was used to assign index dates to the “unexposed” cohort. Cox proportional hazards models estimated risks of a cardiovascular event or death following an exacerbation adjusted for medical and prescription history and stratified by follow-up time, type of cardiovascular event, exacerbation severity, and rank of exacerbation (first, second, or third).

Results

Among 435,925 patients, 170,236 experienced ≥1 exacerbation. Risk of death was increased for 2 years following an exacerbation and was highest during the first 30 days (any exacerbation hazard ratio (HR)=1.79, 95% CI=1.58—2.04; moderate HR=1.22, 95% CI=1.04—1.43; severe HR=5.09, 95% CI=4.30—6.03). Risks of cardiovascular events were increased for 1 year following an AECOPD and highest in the first 30-days (any exacerbation HR=1.34, 95% CI=1.23—1.46; moderate HR=1.23 (95% CI 1.12—1.35); severe HR=1.93 (95% CI=1.67—2.22)). Each subsequent AECOPD was associated with incrementally higher rates of both death and cardiovascular events.

Conclusion

Risk of death and cardiovascular events was greatest in the first 30 days and rose with subsequent exacerbations. Risks were elevated for 1–2 years following moderate and severe exacerbations, highlighting a sustained increased cardiopulmonary risk associated with exacerbations.

Keywords:

• COPD
• cardiopulmonary
• cardiac events
• epidemiology
• longitudinal studies

Abbreviations

COPD, Chronic obstructive pulmonary disease; AECOPD, acute exacerbation of COPD; CVD, cardiovascular disease; CV, cardiovascular; SES, socioeconomic status; SABA, short-acting beta-2 agonist; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; MI, myocardial infarction; HR, hazard ratio; CI, confidence interval; SMD, standardized mean difference; SD, standard deviation; QCCI, Quan-Charlson Comorbidity index; NDI, National death index; IV, intravenous; COVID-19, Coronavirus Disease of 2019; ED, emergency department; HIRD, Healthcare Integrated Research Database.

Data Sharing Statement

Medical and prescription data on the study population are de-identified claims data from Elevance Health insurance plans. These data are owned by Elevance Health and are not publicly available. Variables on the social determinants of health were derived from the American Community Survey, which can be found through the US Census Bureau. Death data from the National Death Index was collected from the Centers for Disease Control and Prevention.

Ethics Approval

The Western Institutional Review Board (WIRB)-Copernicus Group (WCG) Institutional Review Board approved the HIPAA waiver of authorization (IRB tracking number 20221832) for the use and disclosure of protected health information to link patients to the NDI as necessary for conduct of this research. Carelon Research accesses the data in a manner that complies with federal and state laws and regulations, including those related to the privacy and security of individually identifiable health information.

Acknowledgments

The authors would like to thank Meghan Barczewski and Nicole Fournakis for project management support and Elizabeth Marks for editorial support of this manuscript.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

KD, SL, AT, and AN are employees of Carelon Research, Inc., which received funding for the conduct of this study from AstraZeneca. KD and SL are stockholders of Elevance Health. MP, KR CN, and NF are employees and stockholders of AstraZeneca. DM has received payment for consultant services from AstraZeneca and GSK; personal fees from Up to Date, personal fees from Genentech; and has been an expert witness for the Schlesinger Law Firm. GC has received research grant funding and payment for consultant services from AstraZeneca, GSK, and Chiesi Farmaceutici, and received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pulmonx. The authors report no other conflicts on interest in this work.

Additional information

Funding

This study was funded by AstraZeneca.