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

• Published in: Respiratory research 2023-09, Vol.24 (1), p.1-239, Article 239
• Main Authors: Chen, Chun-Yu, Pan, Sheng-Wei, Hsu, Chia-Chen, Liu, Jason J, Kumamaru, Hiraku, Dong, Yaa-Hui
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors (muscarinic); Adrenergic beta agonists; Angina; Antagonists; Cardiovascular disease; Cardiovascular diseases; Cardiovascular events; Cerebral infarction; Chronic obstructive pulmonary disease; Codes; Cohort analysis; Cohort study; Complications and side effects; Confidence intervals; Congestive heart failure; Corticoids; Corticosteroids; Dosage and administration; Drug therapy; Drug therapy, Combination; Fixed-dose combinations (FDC); Health risks; Initiators; Ischemia; Long-acting β2 agonists/inhaled corticosteroids (LABA/ICS); Long-acting β2 agonists/long-acting muscarinic antagonists (LABA/LAMA); Lung diseases; Lung diseases, Obstructive; Muscarinic antagonists; Myocardial infarction; National health insurance; Obstructive lung disease; Pharmacy; Pneumonia; Population studies; Population-based studies; Prevention; Regression analysis; Regression models; Risk factors; Safety; Statistical analysis; Stroke; Subgroups
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-023-02545-9

Background Use of combinations of long-acting [beta].sub.2 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. Keywords: Chronic obstructive pulmonary disease, Long-acting [beta].sub.2 agonists/long-acting muscarinic antagonists (LABA/LAMA), Long-acting [beta].sub.2 agonists/inhaled corticosteroids (LABA/ICS), Fixed-dose combinations (FDC), Cardiovascular events, Cohort study, Target trial emulation framework