Lamiae Grimaldi-Bensouda1, Heiner Wedemeyer2, Johannes Wiegand3, Ansgar W Lohse4, Jacques Benichou5, Michel Rossignol6, Dominique Larrey7, Lucien Abenhaim8, Thierry Poynard9, Eckart Schott10. 1. Pharmacoepidemiology, LA-SER, Paris, France, and Honorary Associate Professor, London School of Hygiene and Tropical Medicine, London, United Kingdom. Electronic address: lgrimaldi@laser-core.com. 2. Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany. 3. Department of Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany. 4. Department of Internal Medicine I, Gastroenterology, Hepatology and Infectious Diseases, Hamburg University Medical Center, Hamburg, Germany. 5. Department of Biostatistics, Rouen University Hospital, and INSERM U657, Institute for Biomedical Research, University of Rouen, Rouen, France. 6. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. 7. Montpellier School of Medicine, IRB-INSERM1040, Montpellier, France. 8. LA-SER Europe Limited and Department of Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom. 9. Groupe Hospitalier Pitié-Salpétrière, Department of Hepatology, AP-HP and Institute of Cardiometabolism and Nutrition (ICAN), INSERM, Paris, France. 10. Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité, Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
Abstract
BACKGROUND: Spontaneous reports of acute liver injuries (ALI) in patients taking dronedarone triggered an EMA alert in 2011. This study aimed to assess the risk of ALI for class III antiarrhythmic drugs controlling for the use of other potential ALI-inducing drugs. METHODS: Between 2010 and 2014, consecutive ALI cases (≥50 years-old) were identified across Germany. ALI was 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/symptoms of ALI, excluding other liver diseases. Recruited community controls were matched to cases on gender, age and inclusion date. Exposure to antiarrhythmic drugs and co-medication up to 2 years before ALI onset was informed by patients and confirmed by physicians' prescriptions. Adjusted Odds Ratios (aOR) were obtained from conditional 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 to class III antiarrhythmic drugs was 4.0% in cases and 1.5% in controls, aOR = 3.6 (95% CI: 1.6-8.4). Associations with 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, and results were robust to case definitions. Continued vigilance is needed for patients taking these drugs.
BACKGROUND: Spontaneous reports of acute liver injuries (ALI) in patients taking dronedarone triggered an EMA alert in 2011. This study aimed to assess the risk of ALI for class III antiarrhythmic drugs controlling for the use of other potential ALI-inducing drugs. METHODS: Between 2010 and 2014, consecutive ALI cases (≥50 years-old) were identified across Germany. ALI was 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/symptoms of ALI, excluding other liver diseases. Recruited community controls were matched to cases on gender, age and inclusion date. Exposure to antiarrhythmic drugs and co-medication up to 2 years before ALI onset was informed by patients and confirmed by physicians' prescriptions. Adjusted Odds Ratios (aOR) were obtained from conditional 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 to class III antiarrhythmic drugs was 4.0% in cases and 1.5% in controls, aOR = 3.6 (95% CI: 1.6-8.4). Associations with 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, and results were robust to case definitions. Continued vigilance is needed for patients taking these drugs.
Authors: Artak Khachatryan; Jose L Merino; Francisco Jose de Abajo; Giovanni L Botto; Paulus Kirchhof; Guenter Breithardt; Bruce Stambler; Lucien Abenhaim; Lamiae Grimaldi-Bensouda Journal: Europace Date: 2022-07-15 Impact factor: 5.486