Magdalene M Assimon1, Patrick H Pun2,3, Lily Chin-Hua Wang4, Sana M Al-Khatib3,5, M Alan Brookhart6, David J Weber7, Wolfgang C Winkelmayer8, Jennifer E Flythe1,4. 1. University of North Carolina Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, UNC School of Medicine, Chapel Hill. 2. Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. 3. Duke Clinical Research Institute, Durham, North Carolina. 4. Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill. 5. Division of Cardiology, Duke University Medical Center, Durham, North Carolina. 6. Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina. 7. Division of Division of Infectious Diseases, Department of Medicine, UNC School of Medicine, Chapel Hill, North Carolina. 8. Selzman Institute for Kidney Health, Section of Nephrology, Baylor College of Medicine, Houston, Texas.
Abstract
Importance: Respiratory fluoroquinolone antibiotics are some of the most common medications with QT interval-prolonging potential prescribed to patients with hemodialysis-dependent kidney failure-individuals who have a very high risk of sudden cardiac death (SCD). To date, there have been no large-scale, population-specific studies evaluating the cardiac safety of respiratory fluoroquinolones in the hemodialysis population. Objective: To investigate the cardiac safety of respiratory fluoroquinolones among individuals with hemodialysis-dependent kidney failure. Design, Setting, and Participants: A retrospective cohort study examining safety using an active comparator new-user design was conducted using administrative claims data from a US-wide kidney failure registry from January 1, 2007, to December 31, 2016, including 264 968 Medicare beneficiaries receiving in-center maintenance hemodialysis. Data analysis was performed from January 4 to August 16, 2021. Exposures: Respiratory fluoroquinolone (levofloxacin or moxifloxacin) vs amoxicillin-based (amoxicillin or amoxicillin with clavulanic acid) antibiotic treatment. Main Outcomes and Measures: Sudden cardiac death within 5 days of outpatient initiation of a study antibiotic. Inverse probability of treatment-weighted survival models to estimate hazard ratios (HRs), risk differences (RDs), and corresponding 95% CIs. Death due to a cause other than SCD was treated as a competing event. Fracture was considered as a negative control outcome. Results: The study cohort included 264 968 unique in-center hemodialysis patients and 626 322 study antibiotic treatment episodes: 251 726 respiratory fluoroquinolone treatment episodes (40.2%) and 374 596 amoxicillin-based treatment episodes (59.8%). Of the 264 968 patients, 135 236 (51.0%) were men, and the mean (SD) age was 61 (15) years. Respiratory fluoroquinolone vs amoxicillin-based antibiotic treatment was associated with a higher relative and absolute 5-day risk of SCD (weighted HR, 1.95; 95% CI, 1.57-2.41; and weighted RD per 100 000 treatment episodes, 44.0; 95% CI, 31.0-59.2). Respiratory fluoroquinolone vs amoxicillin-based antibiotic treatment was not associated with the 5-day risk of fracture. Conclusions and Relevance: In this study, compared with amoxicillin-based antibiotic treatment, respiratory fluoroquinolone treatment was associated with a higher short-term risk of SCD among patients with hemodialysis-dependent kidney failure. This finding suggests that decisions between the use of respiratory fluoroquinolones and amoxicillin-based antibiotics should be individualized, with prescribers considering both the clinical benefits and potential cardiac risks.
Importance: Respiratory fluoroquinolone antibiotics are some of the most common medications with QT interval-prolonging potential prescribed to patients with hemodialysis-dependent kidney failure-individuals who have a very high risk of sudden cardiac death (SCD). To date, there have been no large-scale, population-specific studies evaluating the cardiac safety of respiratory fluoroquinolones in the hemodialysis population. Objective: To investigate the cardiac safety of respiratory fluoroquinolones among individuals with hemodialysis-dependent kidney failure. Design, Setting, and Participants: A retrospective cohort study examining safety using an active comparator new-user design was conducted using administrative claims data from a US-wide kidney failure registry from January 1, 2007, to December 31, 2016, including 264 968 Medicare beneficiaries receiving in-center maintenance hemodialysis. Data analysis was performed from January 4 to August 16, 2021. Exposures: Respiratory fluoroquinolone (levofloxacin or moxifloxacin) vs amoxicillin-based (amoxicillin or amoxicillin with clavulanic acid) antibiotic treatment. Main Outcomes and Measures: Sudden cardiac death within 5 days of outpatient initiation of a study antibiotic. Inverse probability of treatment-weighted survival models to estimate hazard ratios (HRs), risk differences (RDs), and corresponding 95% CIs. Death due to a cause other than SCD was treated as a competing event. Fracture was considered as a negative control outcome. Results: The study cohort included 264 968 unique in-center hemodialysis patients and 626 322 study antibiotic treatment episodes: 251 726 respiratory fluoroquinolone treatment episodes (40.2%) and 374 596 amoxicillin-based treatment episodes (59.8%). Of the 264 968 patients, 135 236 (51.0%) were men, and the mean (SD) age was 61 (15) years. Respiratory fluoroquinolone vs amoxicillin-based antibiotic treatment was associated with a higher relative and absolute 5-day risk of SCD (weighted HR, 1.95; 95% CI, 1.57-2.41; and weighted RD per 100 000 treatment episodes, 44.0; 95% CI, 31.0-59.2). Respiratory fluoroquinolone vs amoxicillin-based antibiotic treatment was not associated with the 5-day risk of fracture. Conclusions and Relevance: In this study, compared with amoxicillin-based antibiotic treatment, respiratory fluoroquinolone treatment was associated with a higher short-term risk of SCD among patients with hemodialysis-dependent kidney failure. This finding suggests that decisions between the use of respiratory fluoroquinolones and amoxicillin-based antibiotics should be individualized, with prescribers considering both the clinical benefits and potential cardiac risks.
Authors: Gary J Noel; Jaya Natarajan; Shuchean Chien; Thomas L Hunt; Daniel B Goodman; Robert Abels Journal: Clin Pharmacol Ther Date: 2003-04 Impact factor: 6.875
Authors: Flory Tsobo Muanda; Manish M Sood; Matthew A Weir; Jessica M Sontrop; Fatemeh Ahmadi; Elisa Yoo; Richard B Kim; Michael S Silverman; Gregory A Knoll; Amit X Garg Journal: JAMA Netw Open Date: 2022-08-01