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Association of QT-Prolonging Medication Use in CKD with Electrocardiographic Manifestations
Soren Snitker1, Rebecca M Doerfler, Elsayed Z Soliman
1Due to the number of contributing authors, the affiliations are provided in the Supplemental Material .
Insights
Many drugs used in chronic kidney disease (CKD) prolong the QT interval. Eight QT-prolonging medications, including amiodarone and metolazone, were significantly associated with QT prolongation in CKD patients.
Area of Science:
- Nephrology
- Cardiology
- Clinical Pharmacology
Background:
- Several medications commonly prescribed for patients with chronic kidney disease (CKD) have the potential to prolong the electrocardiographic QT interval.
- This risk is particularly concerning in CKD patients due to potential electrolyte disturbances and altered drug metabolism.
Purpose of the Study:
- To examine the utilization of QT-prolonging medications in predialysis CKD patients.
- To investigate the association between these medications and QT interval duration in this population.
Main Methods:
- Analysis of data from 3252 participants in the Chronic Renal Insufficiency Cohort study.
- Electrocardiograms (ECGs) and medication data were collected between 2003 and 2011.
- Focus on QT-prolonging drugs used in >=100 visits, diuretics, and proton pump inhibitors, with adjustments for comorbidities, potassium, and calcium.
Main Results:
- The mean corrected QT interval was 414±21 ms, with prolongation (≥450 ms) in 4.6% of ECGs.
- 76% of visits involved QT-prolonging medications; 33% involved two or more.
- Eight medications, including amiodarone (+10 ms) and metolazone (+7 ms), showed significant QT prolongation after adjustments. Diuretics like metolazone and furosemide were associated with QT changes, partly due to electrolyte shifts.
Conclusions:
- The use of QT-prolonging medications is prevalent in patients with CKD.
- The safety implications of these drug-induced QT changes warrant careful consideration in this high-risk patient group.
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.
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