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: -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).