LAMA/LABA Combos Tied to Varying Adverse Events in COPD LAMA/LABA Combos Tied to Varying Adverse Events in COPD

The risk for severe adverse events for patients with chronic obstructive pulmonary disease was significantly lower among those treated with glycopyrronium/indacaterol or umeclidinium/vilanterol compared with those treated with tiotropium/olodaterol, based on data from nearly 45,000 individuals.

Fixed-dose combinations (FDCs) of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) remain the foundation of treatment for chronic obstructive pulmonary disease (COPD), but concerns persist about potentially increased risk for cardiovascular events, especially among new users, wrote Ching-Fu Weng, MD, PhD, of Hsinchu Cathay General Hospital, Hsinchu, Taiwan, and colleagues.

Data comparing the incidence of severe adverse events among different LAMA/LABA combinations are lacking, they said.

In a study published in the journal Chest, the researchers reviewed claims data from the National Health Insurance Research Database and mortality data from the National Death Registry, both in Taiwan, from 2010-2019.

The study population included 44,498 patients with COPD aged 40 years and older who were new users of any of three available FDCs between January 2015, and June 2019. Patients with concomitant LAMA and LABA in their previous 12 months were excluded. The FDCs were glycopyrronium/indacaterol (GLY/IND), umeclidinium/vilanterol (UMEC/VI), and tiotropium/olodaterol (TIO/OLO). GLY/IND was prescribed to 15,586 patients, 20,460 patients got UMEC/VI, and 8452 patients received TIO/OLO. Baseline characteristics were similar among the treatment groups.

The primary outcome of severe adverse events was defined as hospitalization or an emergency department visit with a primary diagnosis of COPD or a secondary diagnosis of a severe AE; the secondary outcome was one of several cardiovascular events including acute myocardial infarction, heart failure, or arrhythmia. The median follow-up period was 6 months for the UMEC/VI and GLY/IND groups, and 60 days for the TIO/OLO group.

During the follow-up period, the incidence of severe AEs was lower in the UMEC/VI group compared with the TIO/OLO group (17.85 vs 29.32 per 100 person-years, hazard ratio [HR], 0.76). Similarly, the incidence of severe AEs was lower in the GLY/IND group compared with the TIO/OLO group (15.54 vs 25.53 per 100 person-years, HR, 0.77). The incidence and risk for any severe AEs was similar between the UMEC/IV and GLY/IND groups.

In a sensitivity analysis, the between-group differences decreased when both severe and moderate AEs were included or in an intent-to-treat analysis, the researchers noted. However, effectiveness remained similar for the UMEC/VI and GLY/IND groups, they said.

For the secondary outcome of cardiovascular events, patients in the GLY/IND group had a significantly lower rate compared with the TIO/OLO group (2.49 vs. 4.28 per 100 person-years, HR 0.70), but this difference vanished when the follow-up was 6 months or less. No significant differences appeared in cardiovascular events between the UMEC/VI and GLY/IND groups or between the UMEC/VI and TIO/OLO groups.

The findings were limited by several factors including the lack of complete clinical information from the database to assess COPD severity, the inability to control for such variables as smoking history and inhaler technique, and the inclusion of only three FDCs, the researchers noted. In addition, actual patient adherence to medication was unknown, they said.

However, the current study offers the first direct comparison of cardiovascular events among three common LAMA/LABA FDCs in COPD, and the differences may inform clinical decision-making, they concluded.

The study was supported in part by the Ministry of Science and Technology, Taiwan. The researchers reported no relevant financial relationships.

Chest. Published online November 25, 2022. Abstract

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