Abstract
BACKGROUND: Spontaneous reports of acute liver injuries (ALI) in patients taking dronedarone triggered an EMAalert in 2011. This study aimed to assess the risk of ALI for class III antiarrhythmic drugs controlling for the useof other potential ALI-inducing drugs.METHODS: Between 2010 and 2014, consecutive ALI cases (≥50 years-old) were identified across Germany. ALIwas defined as a new increase in at least one of the transaminases≥3 times the upper limit of normal (ULN)or≥2 ULN if alkaline phosphatase, with (“definite”case) or without (“biochemical”case) suggestive signs/symp-toms of ALI, excluding other liver diseases. Recruited community controls were matched to cases on gender, ageand inclusion date. Exposure to antiarrhythmic drugs and co-medication up to 2 years before ALI onset was in-formed by patients and confirmed by physicians' prescriptions. Adjusted Odds Ratios (aOR) were obtained fromconditional multivariable logistic regressions, adjusted for a multivariate disease risk score and co-medication.RESULTS: 252 cases and 1081 matched controls were included (59.1% females; mean age: 64 years). Exposure toclass III antiarrhythmic drugs was 4.0% in cases and 1.5% in controls, aOR = 3.6 (95% CI: 1.6–8.4). Associationswith exposure to dronedarone and amiodarone were respectively 3.1 (95% CI: 0.7–14. 8) and 5.90 (1.7–20.0).Restricting the analysis to definite or severe ALI cases did not change these results.CONCLUSIONS: Class III antiarrhythmic drugs were associated with ALI, amiodarone displaying the highest risk, andresults were robust to case definitions. Continued vigilance is needed for patients taking these drugs