Analysis of Respiratory Fluoroquinolones and the Risk of Sudden Cardiac Death Among Patients Receiving Hemodialysis.

Abstract

Importance\nRespiratory 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.\n\n\nObjective\nTo investigate the cardiac safety of respiratory fluoroquinolones among individuals with hemodialysis-dependent kidney failure.\n\n\nDesign, Setting, and Participants\nA 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\u202f968 Medicare beneficiaries receiving in-center maintenance hemodialysis. Data analysis was performed from January 4 to August 16, 2021.\n\n\nExposures\nRespiratory fluoroquinolone (levofloxacin or moxifloxacin) vs amoxicillin-based (amoxicillin or amoxicillin with clavulanic acid) antibiotic treatment.\n\n\nMain Outcomes and Measures\nSudden 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.\n\n\nResults\nThe study cohort included 264\u202f968 unique in-center hemodialysis patients and 626\u202f322 study antibiotic treatment episodes: 251\u202f726 respiratory fluoroquinolone treatment episodes (40.2%) and 374\u202f596 amoxicillin-based treatment episodes (59.8%). Of the 264\u202f968 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\u202f000 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.\n\n\nConclusions and Relevance\nIn 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.