RATIONALE: Aclidinium bromide is an inhaled long-acting anticholinergic (LAMA) approved as a maintenance bronchodilator to relieve symptoms in adults with COPD. There is a potential safety concern related to an increase on mortality with the use of LAMA medications. We conducted a cohort and nested case-control study to compare the risk of all-cause mortality among users of aclidinium and other COPD medications with the risk among users of long-acting beta-agonists (LABA).
METHODS: We identified patients with COPD aged 40 years or older starting treatment with aclidinium, tiotropium, Other LAMA (glycopyrronium, umeclidinium), LABA/inhaled corticosteroids (LABA/ICS), or LABA, in the Clinical Practice Research Datalink (CPRD) in the UK, from September 2012 through March 2017. Deaths were identified in the Hospital Episode Statistics, the Office for National Statistics, and general practitioner’s records from the CPRD. Deaths with inconsistent information between data sources were validated through review of clinical information. Each case (death) was matched to four controls on age, sex, and year of cohort entry. Age- and sex-standardized mortality rates were estimated for current use of each study medication. Relative risks (RRs) for mortality were adjusted by smoking, COPD severity, and other risk factors.
RESULTS: The study included 3,555 users of aclidinium, 19,413 users of tiotropium, 5,308 users of other LAMA, 21,718 users of LABA/ICS, and 4,797 users of LABA. Of 3,822 deaths identified, 3,819 (99.9%) were confirmed. Age- and sex-standardized mortality rates per 1,000 person-years of current use were 32.91 for aclidinium, 43.76 for tiotropium, 37.97 for Other LAMA, 47.14 for LABA/ICS, and 38.12 for LABA. A total of 3,808 confirmed deaths (99.7%) were matched to 15,207 controls. Crude and adjusted RRs of mortality comparing each study medication with LABA are presented in Table 1.
CONCLUSIONS: These results indicate that the use of aclidinium, tiotropium, Other LAMA, or LABA/ICS is not associated with an increased risk of all-cause mortality compared with the use of LABA. Further studies on the risk of cardiovascular endpoints are ongoing.
