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

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.

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