(C-227) Evaluating The Risk of Arrhythmias in Patients With COPD Treated With Aclidinium and Aclidinium/Formoterol and Other Inhaled Bronchodilators

Background: Aclidinium/formoterol is a bronchodilator approved to relieve symptoms of COPD in adults. This study is part of a PASS program to evaluate cardiovascular safety of aclidinium and aclidinium/formoterol (EUPAS13616).

Objectives: To estimate incidence rates and adjusted incidence rate ratios (adj-IRRs) of any cardiac arrhythmia (ACA), atrial fibrillation (AF), and severe ventricular arrhythmias (SVA) in new users of aclidinium compared with new users of LABA and other LAMA and in new users of aclidinium/formoterol compared with new users of LABA and LAMA/LABA.

Methods: This study included patients with COPD aged 40+ years who initiated select COPD medications in the UK CPRD from 2015 to 2021. Poisson regression models were used to estimate the adj-IRRs. Current use was defined as the sum of all episodes of continuous use.

Results: New users were: aclidinium/formoterol=7,682; LAMA/LABA=30,974; LABA/ICS=71,104; LAMA/LABA/ICS=31,238; aclidinium=11,126; tiotropium=54,694; other LAMA=29,564; LABA=11,766. When comparing the study medications with LABA during current use, the adj-IRRs (95% CI) for aclidinium and aclidinium/formoterol, respectively, were 1.16 (0.78-1.74) and 2.08 (1.36-3.18) for ACA, 1.10 (0.71-1.71) and 1.85 (1.15-3.00) for AF, and 0.31 (0.05-1.73) and 1.17 (0.29-4.71) for SVA. When comparing with LAMAs during the first episode of continuous current single use, the adj-IRRs for ACA and AF were 1.46 (0.93-2.29) and 1.57 (0.94-2.62) for aclidinium vs. other LAMA, and 2.15 (1.33-3.49) and 1.79 (0.96-3.33) for aclidinium/formoterol vs. LAMA/LABA. For short duration of use ( < 6 months), the adj-IRRs for aclidinium/formoterol vs. for LAMA/LABA were 1.36 (0.68-2.73) for ACA and 0.97 (0.37-2.54) for AF. IRRs for SVA were not evaluable.

Conclusions: Aclidinium and aclidinium/formoterol showed an increased risk of arrhythmias compared with other study medications. The results cannot be explained by differences between LAMAs in terms of pharmacokinetics, pharmacodynamics, or clinical effectiveness. However, aclidinium users in this study had different baseline characteristics that may confer a higher risk of COPD exacerbations or arrhythmias, and COPD exacerbations increase the risk of arrhythmias. Therefore, results may be affected by some degree of unmeasured confounding and time-varying confounding due to exacerbations occurring during follow-up. In addition, the small numbers resulted in low precision of the estimates. The absence of an increased risk of AF, but not of ACA, during short duration of use of aclidinium/formoterol compared with LAMA/LABA, may reflect an increase at drug initiation in the risk of arrhythmias other than AF or SVAs, most likely paroxysmal supraventricular tachycardias and other unspecified arrhythmias.