PT  - JOURNAL ARTICLE
AU  - Gianluca Trifirò
AU  - Maria de Ridder
AU  - Janet Sultana
AU  - Alessandro Oteri
AU  - Peter Rijnbeek
AU  - Serena Pecchioli
AU  - Giampiero Mazzaglia
AU  - Irene Bezemer
AU  - Edeltraut Garbe
AU  - Tania Schink
AU  - Elisabetta Poluzzi
AU  - Trine Frøslev
AU  - Mariam Molokhia
AU  - Igor Diemberger
AU  - Miriam C.J.M. Sturkenboom
TI  - Use of azithromycin and risk of ventricular arrhythmia
AID  - 10.1503/cmaj.160355
DP  - 2017 Apr 18
TA  - Canadian Medical Association Journal
PG  - E560--E568
VI  - 189
IP  - 15
4099  - http://www.cmaj.ca/content/189/15/E560.short
4100  - http://www.cmaj.ca/content/189/15/E560.full
SO  - CMAJ2017 Apr 18; 189
AB  - 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 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.RESULTS: We 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.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.