A methodological comparison of two European primary care databases and replication in a US claims database: inhaled long-acting beta-2-agonists and the risk of acute myocardial infarction
Maciel Afonso, Ana; Schmiedl, S.; Becker, Claudia; Tcherny-Lessenot, S.; Primatesta, P.; Plana, E.; Souverein, P.; Wang, Y.; Korevaar, J.C.; Hasford, J.; Reynolds, R.; de Groot, M.C.H.; Schlienger, R.; Klungel, O.; Rottenkolber, M.
(2016) European Journal of Clinical Pharmacology, volume 72, issue 9, pp.
(Article)
Abstract
Purpose: Results from observational studies on inhaled long-acting beta-2-agonists (LABA) and acute myocardial infarction (AMI) risk are conflicting, presumably due to variation in methodology. We aimed to evaluate the impact of applying a common study protocol on consistency of results in three databases. Methods: In the primary analysis, we included
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patients from two GP databases (Dutch—Mondriaan, UK—CPRD GOLD) with a diagnosis of asthma and/or COPD and at least one inhaled LABA or a “non-LABA inhaled bronchodilator medication” (short-acting beta-2-agonist or short-/long-acting muscarinic antagonist) prescription between 2002 and 2009. A claims database (USA—Clinformatics) was used for replication. LABA use was divided into current, recent (first 91 days following the end of a treatment episode), and past use (after more than 91 days following the end of a treatment episode). Adjusted hazard ratios (AMI-aHR) and 95 % confidence intervals (95 % CI) were estimated using time-dependent multivariable Cox regression models stratified by recorded diagnoses (asthma, COPD, or both asthma and COPD). Results: For asthma or COPD patients, no statistically significant AMI-aHRs (age- and sex-adjusted) were found in the primary analysis. For patients with both diagnoses, a decreased AMI-aHR was found for current vs. recent LABA use in the CPRD GOLD (0.78; 95 % CI 0.68–0.90) and in Mondriaan (0.55; 95 % CI 0.28–1.08), too. The replication study yielded similar results. Adjusting for concomitant medication use and comorbidities, in addition to age and sex, had little impact on the results. Conclusions: By using a common protocol, we observed similar results in the primary analysis performed in two GP databases and in the replication study in a claims database. Regarding differences between databases, a common protocol facilitates interpreting results due to minimized methodological variations. However, results of multinational comparative observational studies might be affected by bias not fully addressed by a common protocol.
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Keywords: Acute myocardial infarction, Long-acting beta-2-agonists, Methodological comparison, Secondary data analysis, acute heart infarction, asthma, chronic obstructive lung disease, clinical study, comorbidity, confidence interval, controlled study, data analysis, data base, diagnosis, disease model, exposure, hazard ratio, human, observational study, prescription, primary medical care, proportional hazards model, replication study, beta 2 adrenergic receptor stimulating agent, bronchodilating agent, gold, muscarinic receptor blocking agent, Taverne
ISSN: 0031-6970
Publisher: Springer
(Peer reviewed)