Evaluating Arrhythmia Risk in Patients with Chronic Obstructive Pulmonary Disease Treated with Aclidinium/Formoterol Fumarate and Other Inhaled Bronchodilators: A Post-Authorization Safety Study.

PURPOSE: A post-authorization safety study program examined the cardiovascular safety of the long-acting muscarinic antagonist (LAMA) aclidinium bromide monotherapy and the LAMA/long-acting β2-agonist (LABA) aclidinium bromide/formoterol fumarate. We assessed frequency and risk of any cardiac arrhythmias (CA), atrial fibrillation (AF), and serious ventricular arrhythmias (SVA) in aclidinium and aclidinium/formoterol users.

PATIENTS AND

METHODS

This population-based cohort study included adults with chronic obstructive pulmonary disease (COPD) initiating COPD medications in the UK Clinical Practice Research Datalink Aurum database (Jan 2015-Mar 2021). CA, AF, and SVA incidence rate ratios (IRR) were estimated using Poisson regression models for continuous current users initiating aclidinium and aclidinium/formoterol versus LABA, and during the first episode of current single use for aclidinium versus LAMA and aclidinium/formoterol versus LAMA/LABA, adjusting for clinically relevant covariables.

RESULTS

The study included a total of 248,148 initiators. For CA and AF, respectively, adjusted IRRs (95% confidence intervals [CIs]) ranged from 0.98 (0.69-1.41) for LAMA/LABA to 2.08 (1.36-3.18) for aclidinium/formoterol and from 0.83 (0.55-1.24) for LAMA/LABA to 1.85 (1.15-3.00) for aclidinium/formoterol versus current LABA use. For current single use (first episode), adjusted IRRs (95% CIs) for CA and AF were 1.46 (0.93-2.29) and 1.57 (0.94-2.62) for aclidinium versus other LAMAs, and 2.15 (1.33-3.49) and 1.79 (0.96-3.33) for aclidinium/formoterol versus LAMA/LABA, respectively. There were few SVA events.

CONCLUSION

CA and AF risks were increased for most study medications compared with LABA. Increased risks of CA and AF for several medications relative to LABA, LAMA, or LAMA/LABA may be driven by differences in baseline characteristics (eg, COPD severity).