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

CRIC Study Investigators

Research output: Contribution to journalArticle

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

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Metolazone
Furosemide
Heart Rate
Calcium
Potassium
Citalopram
Proton Pump Inhibitors
Diuretics
Electrocardiography
Hydroxyzine
Sodium Chloride Symporter Inhibitors
Spironolactone
Amiodarone
Fluoxetine
Chronic Renal Insufficiency
Electrolytes
Comorbidity
Safety
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

Cite this

Association of QT-prolonging medication use in CKD with electrocardiographic manifestations. / CRIC Study Investigators.

In: Clinical Journal of the American Society of Nephrology, Vol. 12, No. 9, 07.09.2017, p. 1409-1417.

Research output: Contribution to journalArticle

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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.",
author = "{CRIC Study Investigators} and Soren Snitker and Doerfler, {Rebecca M.} and Soliman, {Elsayed Z.} and Rajat Deo and {St. Peter}, {Wendy L.} and Susan Kramlik and Fischer, {Michael J.} and Sankar Navaneethan and Patrice Delafontaine and Bernard Jaar and Akinlolu Ojo and Makos, {Gail K.} and Anne Slaven and Weir, {Matthew R.} and Min Zhan and Fink, {Jeffrey C.}",
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T1 - Association of QT-prolonging medication use in CKD with electrocardiographic manifestations

AU - CRIC Study Investigators

AU - Snitker, Soren

AU - Doerfler, Rebecca M.

AU - Soliman, Elsayed Z.

AU - Deo, Rajat

AU - St. Peter, Wendy L.

AU - Kramlik, Susan

AU - Fischer, Michael J.

AU - Navaneethan, Sankar

AU - Delafontaine, Patrice

AU - Jaar, Bernard

AU - Ojo, Akinlolu

AU - Makos, Gail K.

AU - Slaven, Anne

AU - Weir, Matthew R.

AU - Zhan, Min

AU - Fink, Jeffrey C.

PY - 2017/9/7

Y1 - 2017/9/7

N2 - 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.

AB - 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.

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