BACKGROUND: Results from multiple observational studies on inhaled long-acting beta-2-agonists (LABA) and the risk of acute myocardial infarction (AMI) are conflicting, due to variations in methodological, clinical and health care characteristics. To some extent, the discrepancies in the design might limit the comparability of the results encountered.
OBJECTIVES: To determine the risk of AMI in inhaled LABA users in two European electronic primary care databases using a common study protocol.
METHODS: Patients from the Dutch Mondriaan (1.4 Million) and the UK CPRD (5 Million) databases were included if they had a diagnosis of asthma and/or COPD, and were prescribed at least one inhaled LABA, a short-acting beta-2-agonist (SABA), or a short- or long-acting muscarinic antagonist (SAMA, LAMA) during the study period (2002 to 2009). LABA episodes were divided into current, recent (<91 days after the prescription end date) and past use (≥91 days after the prescription end date). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by using time-dependent multivariable Cox regression models and adjusted for confounders (age, sex, co-morbidities, co-medications). Adjusted HR (HRadj) for current versus recent, and current versus past use associated with the risk of AMI and 95%CI were calculated and stratified by indication (asthma, COPD, and asthma&COPD).
RESULTS: Overall, 656,414 patients in the CPRD and 36,188 patients in the Mondriaan database were included. Patients in the CPRD database had more comorbidities and co-medications when compared to Mondriaan patients. In both Mondriaan and CPRD, among asthma and asthma&COPD patients, no significant differences in the HRadj were found. Among asthma&COPD patients, a significantly decreased AMI risk with HRadj 0.78; 95%CI 0.68–0.90, was only found for the comparison of current LABA versus recent LABA use in the CPRD database, but not significant in the Mondriaan database, HRadj 0.55, 95%CI 0.28–1.08.
CONCLUSIONS: Despite potential differences between databases, using a common protocol that reduced methodological disparities, we found similar AMI HRadj in the two cohorts.
