• Gianluca Trifirò, Maria de Ridder, Janet Sultana, Alessandro Oteri, Peter Rijnbeek, Serena Pecchioli, Giampiero Mazzaglia, Irene Bezemer, Edeltraut Garbe, Tania Schink, Elisabetta Poluzzi, Trine Frøslev, Mariam Molokhia, Igor Diemberger, and Miriam C J M Sturkenboom.
• Department of Medical Informatics (Trifirò, de Ridder, Sultana, Oteri, Rijnbeek, Sturkenboom), Erasmus University Medical Center, Rotterdam, Netherlands; Department of Biomedical and Dental Sciences and Morpho-functional Imaging (Trifirò), and Department of Clinical and Experimental Medicine (Sultana), University of Messina, Messina, Italy; Health Search, Italian College of General Practitioners (Pecchioli, Mazzaglia), Florence, Italy; PHARMO Institute for Drug Outcomes Research (Bezemer), Utrecht, Netherlands; Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH (Garbe, Schink), Bremen, Germany; Department of Medical and Surgical Sciences (Poluzzi), University of Bologna, Bologna, Italy; Department of Clinical Epidemiology (Frøslev), Aarhus University Hospital, Aarhus, Denmark; Department of Primary Care and Public Health Sciences (Molokhia), King's College, London, United Kingdom; Department of Experimental, Diagnostic and Specialty Medicine (Diemberger), University of Bologna, Bologna, Italy trifirog@unime.it.
• CMAJ. 2017 Apr 18; 189 (15): E560-E568.

BackgroundThere are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia.MethodsWe conducted a nested case-control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997-2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders.ResultsWe identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio [OR] 1.97, 95% confidence interval [CI] 1.35-2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48-1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis.InterpretationCurrent azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication.© 2017 Canadian Medical Association or its licensors.

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