Association of QT-Prolonging Medication Use in CKD with Electrocardiographic Manifestations

Clin J Am Soc Nephrol. 2017 Sep 7;12(9):1409-1417. doi: 10.2215/CJN.12991216. Epub 2017 Aug 9.

Abstract

Background and objectives: Several drugs used in CKD can prolong electrocardiographic conduction. We examined the use of electrocardiogram QT-prolonging medications in predialysis CKD and their association with QT duration.

Design, setting, participants, & measurements: In total, 3252 Chronic Renal Insufficiency Cohort participants with 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 potassium and 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 associated with a change in QT interval corrected for heart rate before adjustment for potassium and calcium were metolazone (+8±3 milliseconds), furosemide (+4±1 milliseconds), and spironolactone (-3±3 milliseconds). 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.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_08_09_CJASNPodcast_17_09_b.mp3.

Keywords: Amiodarone; Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction Defect; Citalopram; Diuretics; Electrocardiography; Electrolytes; Fluoxetine; Furosemide; Heart Conduction System; Humans; Hydroxyzine; Metolazone; Potassium; Proton Pump Inhibitors; Renal Dialysis; Renal Insufficiency, Chronic; Sodium Chloride Symporter Inhibitors; Spironolactone; Venlafaxine Hydrochloride.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amiodarone / pharmacology
  • Anti-Arrhythmia Agents / pharmacology
  • Antidepressive Agents, Second-Generation / pharmacology
  • Citalopram / pharmacology
  • Diabetes Complications / complications
  • Diabetes Complications / physiopathology
  • Diuretics / pharmacology*
  • Electrocardiography*
  • Female
  • Fluoxetine / pharmacology
  • Furosemide / pharmacology
  • Heart / physiopathology*
  • Heart Rate
  • Histamine H1 Antagonists / pharmacology
  • Humans
  • Hydroxyzine / pharmacology
  • Male
  • Metolazone / pharmacology
  • Middle Aged
  • Proton Pump Inhibitors / pharmacology
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / physiopathology*
  • Venlafaxine Hydrochloride / pharmacology

Substances

  • Anti-Arrhythmia Agents
  • Antidepressive Agents, Second-Generation
  • Diuretics
  • Histamine H1 Antagonists
  • Proton Pump Inhibitors
  • Fluoxetine
  • Citalopram
  • Hydroxyzine
  • Venlafaxine Hydrochloride
  • Furosemide
  • Amiodarone
  • Metolazone