Comparative cardiovascular safety of LABA/LAMA FDC versus LABA/ICS FDC in patients with chronic obstructive pulmonary disease: a population-based cohort study with a target trial emulation framework

Chun-Yu Chen, Sheng-Wei Pan, Chia-Chen Hsu, Jason Jiashuan Liu, Hiraku Kumamaru, Yaa-Hui Dong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background
Use of combinations of long-acting β2 agonists/long-acting muscarinic antagonists (LABA/LAMA) in patients with chronic obstructive pulmonary disease (COPD) is increasing. Nevertheless, existing evidence on cardiovascular risk associated with LABA/LAMA versus another dual combination, LABA/inhaled corticosteroids (ICS), was limited and discrepant.

Aim
The present cohort study aimed to examine comparative cardiovascular safety of LABA/LAMA and LABA/ICS with a target trial emulation framework, focusing on dual fixed-dose combination (FDC) therapies.

Methods
We identified patients with COPD who initiated LABA/LAMA FDC or LABA/ICS FDC from a nationwide Taiwanese database during 2017–2020. The outcome of interest was a hospitalized composite cardiovascular events of acute myocardial infarction, unstable angina, heart failure, cardiac dysrhythmia, and ischemic stroke. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for composite and individual cardiovascular events after matching up to five LABA/LAMA FDC initiators to one LABA/ICS FDC initiator using propensity scores (PS).

Results
Among 75,926 PS-matched patients, use of LABA/LAMA FDC did not show a higher cardiovascular risk compared to use of LABA/ICS FDC, with a HR of 0.89 (95% CI, 0.78–1.01) for the composite events, 0.80 (95% CI, 0.61–1.05) for acute myocardial infarction, 1.48 (95% CI, 0.68–3.25) for unstable angina, 1.00 (95% CI, 0.80–1.24) for congestive heart failure, 0.62 (95% CI, 0.37–1.05) for cardiac dysrhythmia, and 0.82 (95% CI, 0.66–1.02) for ischemic stroke. The results did not vary substantially in several pre-specified sensitivity and subgroup analyses.

Conclusion
Our findings provide important reassurance about comparative cardiovascular safety of LABA/LAMA FDC treatment among patients with COPD.
Original languageAmerican English
Pages (from-to)239
JournalRespiratory Research
Volume24
Issue number1
DOIs
StatePublished - Sep 2023

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