Language
English
Publication Date
10-19-2022
Journal
Nephrology Dialysis Transplantation
DOI
10.1093/ndt/gfac214
PMID
35793567
PMCID
PMC9585464
PubMedCentral® Posted Date
7-6-2022
PubMedCentral® Full Text Version
Post-print
Abstract
Background: Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs).
Methods: We conducted a cohort study using 2007-2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus < 4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case-control study.
Results: The study included 25 099 patients: 11 107 (44.3%) higher QT-prolonging potential SSRI new users and 13 992 (55.7%) lower QT-prolonging potential SSRI new users. Overall, higher versus lower QT-prolonging potential SSRI use was not associated with SCD [weighted HR 1.03 (95% CI 0.86-1.24)]. However, a greater risk of SCD was associated with higher versus lower QT-prolonging potential SSRI use among patients with baseline potassium gradients ≥4 mEq/l but not among those with gradients < 4 mEq/l [weighted HR 2.17 (95% CI 1.16-4.03) versus 0.95 (0.78-1.16)]. Nested case-control analyses yielded analogous results.
Conclusions: The serum-to-dialysate potassium gradient may modify the association between higher versus lower QT-prolonging SSRI use and SCD among people receiving HD. Minimizing the potassium gradient in the setting of QT-prolonging medication use may be warranted.
Keywords
Humans, United States, Dialysis Solutions, Selective Serotonin Reuptake Inhibitors, Citalopram, Renal Dialysis, Fluoxetine, Sertraline, Fluvoxamine, Cohort Studies, Case-Control Studies, Paroxetine, Potassium, Death, Sudden, Cardiac, hemodialysis, potassium gradient, SSRI, sudden cardiac death, USRDS
Published Open-Access
yes
Recommended Citation
Assimon, Magdalene M; Pun, Patrick H; Al-Khatib, Sana M; et al., "The Modifying Effect of the Serum-to-Dialysate Potassium Gradient on the Cardiovascular Safety of SSRIs in the Hemodialysis Population: A Pharmacoepidemiologic Study" (2022). Faculty and Staff Publications. 4101.
https://digitalcommons.library.tmc.edu/baylor_docs/4101