BACKGROUND: Aclidinium bromide is an inhaled long-acting muscarinic receptor antagonist (LAMA) approved in Europe in 2012 as a maintenance bronchodilator to relieve symptoms of chronic obstructive pulmonary disease (COPD) in adults. This study is part of a postauthorisation safety program to evaluate cardiovascular safety endpoints related to the use of LAMA medications, as described in the aclidinium risk management plan (EUPAS13616).
OBJECTIVES: To estimate incidence rates and adjusted incidence rate ratios (IRRs) for acute myocardial infarction(AMI), stroke, and major adverse cardiac events (MACE, a composite endpoint of first occurrence of AMI,stroke, or community coronary heart disease or cerebrovascular disease death) in new users ofaclidinium, aclidinium/formoterol, tiotropium, other LAMA, long-acting beta-agonists/inhaledcorticosteroids (LABA/ICS), and LAMA/LABA compared with new users of LABA.
METHODS: This population-based cohort included patients with COPD aged ≥40 years initiating COPD medications inthe UK Clinical Practice Research Datalink (CPRD) Aurum database from 2012 to 2019. Poisson regressionmodels were used to estimate the IRR for AMI, stroke, and MACE in users of select COPD medicationsversus LABA, adjusting for clinically relevant covariables.
RESULTS: The study included 11,121 new users of aclidinium, 4,804 of aclidinium/formoterol, 56,198 of tiotropium,23,856 of other LAMA, 17,450 of LAMA/LABA, 70,289 of LABA/ICS, and 13,716 of LABA. During periods ofcontinuous study medication use after initiation (current use), crude incidence rates per 1,000 person-years for AMI ranged from 8.7 for aclidinium/formoterol to 12.4 for LAMA/LABA, for stroke ranged from4.8 for aclidinium/formoterol to 7.2 for LAMA/LABA, and for MACE ranged from 13.5 foraclidinium/formoterol to 19.3 for LAMA/LABA. Using LABA as the reference, adjusted IRRs (95%confidence intervals) were close to 1 for all study drugs for AMI (lowest for aclidinium/formoterol, 0.95[0.60-1.52] and highest for LAMA/LABA, 1.23 [0.91-1.67]), stroke (lowest for aclidinium/formoterol, 0.64[0.39-1.06] and highest for tiotropium, 1.02 [0.81-1.27]), and MACE (lowest for aclidinium, 0.93 [0.75-1.16]and highest for LAMA/LABA, 1.24 [0.97-1.59]).
CONCLUSIONS: Current use of aclidinium, aclidinium/formoterol, tiotropium, other LAMA, LAMA/LABA, or LABA/ICS is notassociated with a clinically meaningful increased or decreased risk of AMI, stroke, or MACE comparedwith the use of LABA.
