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

Cristina Rebordosa,1 Jaume Aguado,1 Jennifer Bartsch,2 Nuria Saigi-Morgui,1 Anne-Elie Carsin,1 Raquel Garcia-Esteban,1 Elena Ignatova,3 Daniel Freedman,3 Susana Perez-Gutthann,1 Elena Rivero-Ferrer1 1RTI Health Solutions, Barcelona, Spain; 2RTI Health Solutions, Research Triangle Park, NC, USA; 3Covis Pharma Gmbh, a Wholly-Owned Subsidiary of Azurity Pharmaceuticals, Inc., Woburn, MA, USACorrespondence: Cristina Rebordosa, RTI Health Solutions, Av. Diagonal, 605, 9-1, Barcelona, 08028, Spain, Tel +34 932 41 77 66, Email crebordosa@rti.orgPurpose: 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).Keywords: aclidinium, arrhythmia, LAMA, LABA, United Kingdom