https://orcid.org/0000-0001-6239-1682
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Abstract
Background
COPD coexists with many concurrent comorbidities. Cardiovascular complications are deemed to be major causes of death in COPD. Although inhaler therapy is the main therapeutic intervention in COPD, cardiovascular events accompanying inhaler therapy require further investigation. Therefore, this study aimed to investigate new development of cardiovascular events according to each inhaler therapy and comorbidities.
Methods
This study analyzed COPD patients (age ≥ 40 years, N = 199,772) from the Health Insurance Review and Assessment Service (HIRA) database in Korea. The development of cardiovascular events, from the index date to December 31, 2020, was investigated. The cohort was eventually divided into three arms: the LAMA/LABA group (N = 28,322), the ICS/LABA group (N = 11,812), and the triple group (LAMA/ICS/LABA therapy, N = 6174).
Results
Multivariable Cox analyses demonstrated that, compared to ICS/LABA therapy, triple therapy was independently associated with the development of ischemic heart disease (HR: 1.22, 95% CI: 1.04–1.43), heart failure (HR: 1.45, 95% CI: 1.14–1.84), arrhythmia (HR: 1.72, 95% CI: 1.41–2.09), and atrial fibrillation/flutter (HR: 2.31, 95% CI: 1.64–3.25), whereas the LAMA/LABA therapy did not show a significant association. Furthermore, emergency room visit during covariate assessment window was independently associated with the development of ischemic heart disease, heart failure, arrhythmia, and atrial fibrillation/flutter (p < 0.05).
Conclusion
Our data suggest that cardiovascular risk should be considered in COPD patients receiving triple therapy, despite the confounding bias resulting from disparities in each group.
Abbreviations
COPD, Chronic obstructive pulmonary disease; CI, confidence intervals; PDE-4 inhibitor, phosphodiesterase-4 inhibitor; HIRA, Health Insurance Review and Assessment Service; HR, Hazard ratio; ICS, inhaled corticosteroid; LABA, long-acting beta-2 agonist; LAMA, long-acting muscarinic antagonist; RCT, randomized clinical trial.
Data Sharing Statement
HIRA is open and public data to which any researcher can get access through the website (https://www.hira.or.kr).
Ethics Approval and Consent to Participate
The present study was approved by the Institutional Review Board of Ajou University Hospital (AJOUIRB-EXP-2021-582). The requirement for informed consent from patients analyzed was waived by the ethical review board.
Acknowledgment
This work was supported by the research program funded from Korea National Institute of Health (Funding code 2016ER670100, 2016ER670101, 2016ER670102, 2018ER67100, 2018ER67101, 2018ER67102, and 2021ER120500), National Research Foundation from Korean Government (NRF-2021R1I1A3056129), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HR16C0001).
The abstract of this paper was presented at the American thoracic society 2023 international conference as a poster presentation with interim findings.
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
All authors have nothing to declare regarding relevant financial activities and relationships/conditions/circumstances that present a potential conflict of interest.