Comparison of Clinical Outcomes Among Different Fixed-Dose Combinations of Long-Acting Muscarinic Antagonists and Long-Acting 132-Agonists in Patients With COPD

BACKGROUND: Researchers have yet to obtain conclusive evidence differentiating among fixed-dose combinations (FDCs) of long-acting muscarinic antagonists (LAMAs) and long -acting M2-agonists (LABAs) for COPD in terms of real-world clinical outcomes.RESEARCH QUESTION: What are the differences between available LAMA/LABA FDCs in the risk of acute exacerbation (AE) and cardiovascular events?STUDY DESIGN AND METHODS: This retrospective cohort study based on a national insurance claims database included patients with COPD $ 40 years of age who were newly prescribed glycopyrronium (GLY)/indacaterol (IND), umeclidinium (UMEC)/vilanterol (VI), or tio-tropium (TIO)/olodaterol (OLO) FDC between January 1, 2015, and June 30, 2019. Pro-pensity score matching and Cox regression models were used to compare outcomes of 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 pa-tients 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, 0.76; 95% CI, 0.68-0.84; GLY/IND vs TIO/OLO: 15.54 vs 25.53 per 100 person-years; hazard ratio, 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 patients with COPD receiving UMEC/VI or GLY/IND than among those receiving TIO/OLO, whereas 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. CHEST 2023; 163(4):799-814