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Background: Researchers have yet to obtain conclusive evidence differentiating among fixed-dose combinations (FDCs) of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) for chronic obstructive pulmonary disease (COPD) in terms of real-world clinical outcomes.Research Question: What are the differences between available LAMA/LABA FDCs on the risk of acute exacerbation and cardiovascular events?Study Design and Methods: This retrospective cohort study based on a national insurance claims database included COPD patients aged 40 and older who were newly prescribed glycopyrronium/indacaterol (GLY/IND), umeclidinium/vilanterol (UMEC/VI), or tiotropium/olodaterol (TIO/OLO) FDC between January 1, 2015, and June 30, 2019. Propensity score matching and Cox regression models were used to compare outcomes of acute exacerbation (AE) and cardiovascular events associated with LAMA/LABA FDC treatment.Results: Among the 44,498 patients identified and included, 15,586 received GLY/IND, 20,460 received UMEC/VI, and 8,452 received TIO/OLO. Baseline characteristics were well balanced after 1:1 matching of UMEC/VI and GLY/IND, 2:1 matching of UMEC/VI and TIO/OLO, and 2:1 matching of GLY/IND and TIO/OLO. Risk of severe AE was lower among patients treated with UMEC/VI or GLY/IND than among those who received TIO/OLO (UMEC/VI vs. TIO/OLO: 17.85 vs. 29.32 per 100 person-years; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.68-0.84; GLY/IND vs. TIO/OLO: 15.54 vs. 25.53 per 100 person-years; HR 0.77, 95% CI 0.67-0.88). In addition, GLY/IND users tended to have a lower risk of cardiovascular events than TIO/OLO users, but the difference dissipated when restricting follow-up to a shorter duration.Interpretation: Our results revealed that the risk of severe AE was lower among COPD patients receiving UMEC/VI or GLY/IND than among those receiving TIO/OLO, while the incidence of cardiovascular events was similar across groups but was slightly lower in GLY/IND users when compared with TIO/OLO users. Further research will be required to confirm these findings. [ABSTRACT FROM AUTHOR]