Association of QT-prolonging medication use in CKD with electrocardiographic manifestations

Soren Snitker, Rebecca M. Doerfler, Elsayed Z. Soliman, Rajat Deo, Wendy L. St. Peter, Susan Kramlik, Michael J. Fischer, Sankar Navaneethan, Patrice Delafontaine, Bernard G. Jaar, Akinlolu Ojo, Gail K. Makos, Anne Slaven, Matthew R. Weir, Min Zhan, Jeffrey C. Fink, CRIC Study Investigators

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background and objectives Several drugs used in CKD can prolong electrocardiographic conduction. We examined the use of electrocardiogramQT-prolongingmedications in predialysisCKDand their associationwith QT duration. Design, setting, participants, &measurements In total, 3252 Chronic Renal Insufficiency Cohort participantswith at least one study electrocardiogram between 2003 and 2011 were included. QT-prolonging medications used in 100 or more visits (n=16, 451 visits) along with diuretics and proton pump inhibitors, given their potential for electrolyte disturbances, were examined for QT interval prolongation. Results Mean QT interval corrected for heart rate was at 414±21 (±SD) milliseconds and prolonged ($450 milliseconds) in 4. 6% of electrocardiograms. QT interval corrected for heart rate was inversely related to serum potassiumand calcium. Medications classified as QT prolonging were taken at 76%of visits, with two or more of these taken at 33% of visits. Of 30 medications examined, eight were associated with statistically significant QT interval corrected for heart rate prolongation after adjustment for comorbidities, potassium, and calcium, including amiodarone (+10±2 milliseconds), metolazone (+7±2 milliseconds), fluoxetine (+4±1 milliseconds), citalopram (+4±1 milliseconds), hydroxyzine (+4±1 milliseconds), escitalopram (+3±2 milliseconds), venlafaxine (+3±1 milliseconds), and furosemide (+3±0 milliseconds). Potassium-depleting diuretics were associated with minimal decrements in potassium (between 0. 1 and 0. 3 mEq/L) and smaller changes in calcium. Diuretics associatedwith a change inQT interval corrected for heart rate before adjustment for potassiumand calciumwere metolazone (+8±3milliseconds), furosemide (+4±1milliseconds), andspironolactone (23±3milliseconds). Most of the QT prolongation associated with metolazone and furosemide, but not spironolactone, remained after adjustment for potassium and calcium. Proton pump inhibitors were not associated with QT prolongation. Conclusions Use of medications associated with QT prolongation is common in CKD; the safety implications of these findings should be considered in these high-risk patients.

Original languageEnglish (US)
Pages (from-to)1409-1417
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Volume12
Issue number9
DOIs
StatePublished - Sep 7 2017

Bibliographical note

Funding Information:
S.S., R.M.D., M.Z., and J.C.F. were supported by National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant R01 DK090008. Funding for the Chronic Renal Insufficiency Cohort (CRIC) Study was obtained under a cooperative agreement from the NIDDK (grants U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported, in part, by Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science NIH/National Center for Advancing Translational Sciences (NCATS) award UL1TR000003, Johns Hopkins University grant UL1 TR-000424, University of Maryland General Clinical Research Center grant M01 RR-16500, the Clinical and Translational Science Collaborative of Cleveland, grant UL1TR000439 from the NCATS component of the NIH and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research grant V 2014.07.28 UL1TR000433, University of Illinois at Chicago Clinical and Translational Science Award grant UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology grantP30GM103337,andKaiserPermanenteNIH/NationalCenterfor Research Resources University of California, San Francisco-Clinical and Translational Science Institute grant UL1 RR-024131.

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