Cargando…
QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis
RATIONALE & OBJECTIVE: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassi...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10127135/ https://www.ncbi.nlm.nih.gov/pubmed/37113163 http://dx.doi.org/10.1016/j.xkme.2023.100618 |
_version_ | 1785030400499777536 |
---|---|
author | Pun, Patrick H. Assimon, Magdalene M. Wang, Lily Al-Khatib, Sana M. Brookhart, M. Alan Weber, David J. Winkelmayer, Wolfgang C. Flythe, Jennifer E. |
author_facet | Pun, Patrick H. Assimon, Magdalene M. Wang, Lily Al-Khatib, Sana M. Brookhart, M. Alan Weber, David J. Winkelmayer, Wolfgang C. Flythe, Jennifer E. |
author_sort | Pun, Patrick H. |
collection | PubMed |
description | RATIONALE & OBJECTIVE: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin. STUDY DESIGN: Retrospective observational cohort study using a new-user study design. SETTING & POPULATION: Adult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017). EXPOSURE: Initiation of azithromycin (or levofloxacin/moxifloxacin) as compared to amoxicillin-based antibiotics (exposure). Serum-to-dialysate potassium gradient (effect modifier). Individual patients could contribute multiple study antibiotic treatment episodes to the analyses. OUTCOMES: Sudden cardiac death (14 days). ANALYTICAL APPROACH: Inverse probability of treatment-weighted survival models to estimate HRs and robust 95% CIs. RESULTS: The azithromycin versus amoxicillin-based antibiotic cohort included 89,379 unique patients with 113,516 azithromycin and 103,493 amoxicillin-based treatment episodes. Azithromycin versus amoxicillin-based antibiotic treatment was associated with a higher risk of sudden cardiac death overall, HR, 1.68; 95% CI, 1.31-2.16. The risk was numerically higher when the baseline serum-to-dialysate potassium gradient was ≥3 mEq/L compared with <3 mEq/L (HR, 2.22; 95% CI, 1.46-3.40 vs HR, 1.43; 95% CI. 1.04-1.96, P(interaction) = 0.07). Analogous analyses in a respiratory fluoroquinolone (levofloxacin/moxifloxacin) versus amoxicillin-based antibiotic cohort with 79,449 unique patients and 65,959 respiratory fluoroquinolone and 103,776 amoxicillin-based treatment episodes yielded similar results. LIMITATIONS: Residual confounding. CONCLUSIONS: Although treatment with azithromycin and, separately, respiratory fluoroquinolones were each associated with a heightened risk of sudden cardiac death, this risk was augmented in the setting of larger serum-to-dialysate potassium gradients. Minimizing the potassium gradient may be an approach to reduce the cardiac risk of these antibiotics. |
format | Online Article Text |
id | pubmed-10127135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-101271352023-04-26 QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis Pun, Patrick H. Assimon, Magdalene M. Wang, Lily Al-Khatib, Sana M. Brookhart, M. Alan Weber, David J. Winkelmayer, Wolfgang C. Flythe, Jennifer E. Kidney Med Original Research RATIONALE & OBJECTIVE: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin. STUDY DESIGN: Retrospective observational cohort study using a new-user study design. SETTING & POPULATION: Adult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017). EXPOSURE: Initiation of azithromycin (or levofloxacin/moxifloxacin) as compared to amoxicillin-based antibiotics (exposure). Serum-to-dialysate potassium gradient (effect modifier). Individual patients could contribute multiple study antibiotic treatment episodes to the analyses. OUTCOMES: Sudden cardiac death (14 days). ANALYTICAL APPROACH: Inverse probability of treatment-weighted survival models to estimate HRs and robust 95% CIs. RESULTS: The azithromycin versus amoxicillin-based antibiotic cohort included 89,379 unique patients with 113,516 azithromycin and 103,493 amoxicillin-based treatment episodes. Azithromycin versus amoxicillin-based antibiotic treatment was associated with a higher risk of sudden cardiac death overall, HR, 1.68; 95% CI, 1.31-2.16. The risk was numerically higher when the baseline serum-to-dialysate potassium gradient was ≥3 mEq/L compared with <3 mEq/L (HR, 2.22; 95% CI, 1.46-3.40 vs HR, 1.43; 95% CI. 1.04-1.96, P(interaction) = 0.07). Analogous analyses in a respiratory fluoroquinolone (levofloxacin/moxifloxacin) versus amoxicillin-based antibiotic cohort with 79,449 unique patients and 65,959 respiratory fluoroquinolone and 103,776 amoxicillin-based treatment episodes yielded similar results. LIMITATIONS: Residual confounding. CONCLUSIONS: Although treatment with azithromycin and, separately, respiratory fluoroquinolones were each associated with a heightened risk of sudden cardiac death, this risk was augmented in the setting of larger serum-to-dialysate potassium gradients. Minimizing the potassium gradient may be an approach to reduce the cardiac risk of these antibiotics. Elsevier 2023-02-15 /pmc/articles/PMC10127135/ /pubmed/37113163 http://dx.doi.org/10.1016/j.xkme.2023.100618 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Pun, Patrick H. Assimon, Magdalene M. Wang, Lily Al-Khatib, Sana M. Brookhart, M. Alan Weber, David J. Winkelmayer, Wolfgang C. Flythe, Jennifer E. QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis |
title | QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis |
title_full | QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis |
title_fullStr | QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis |
title_full_unstemmed | QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis |
title_short | QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis |
title_sort | qt-prolonging antibiotics, serum-to-dialysate potassium gradient, and risk of sudden cardiac death among patients receiving maintenance hemodialysis |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10127135/ https://www.ncbi.nlm.nih.gov/pubmed/37113163 http://dx.doi.org/10.1016/j.xkme.2023.100618 |
work_keys_str_mv | AT punpatrickh qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis AT assimonmagdalenem qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis AT wanglily qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis AT alkhatibsanam qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis AT brookhartmalan qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis AT weberdavidj qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis AT winkelmayerwolfgangc qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis AT flythejennifere qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis |