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ABSTRACT
BACKGROUND: There 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.
METHODS: We conducted a nested casecontrol 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.
RESULTS: We identified 14040688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12874, 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 [Cl] 1.35-2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% Cl 0.48-1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis.
INTERPRETATION: Current 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.
* Cite as: CMAJ 2017 April 18;189:E560-8. doi: 10.1503/cmaj.l60355
Azithromycin is a widely prescribed broad-spectrum macrolide used mainly for the treatment of respiratory and urinary tract bacterial infections. Concerns have been raised recently regarding its arrhythmogenic potential, a risk already known to be associated with the first marketed macrolide, erythromycin.1-6 Several case reports have described QTinterval prolongation,7-9 torsades de pointes10-12 and polymorphic ventricular tachycardia13 following use of azithromycin. Many observational studies have reported conflicting results about the association between azithromycin use and cardiovascular death.14-21 Because the known azithromycin-related cardiac events are related to...