Dataset Information

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

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.

SUBMITTER: Snitker S

PROVIDER: S-EPMC5586585 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Snitker Soren S Doerfler Rebecca M RM Soliman Elsayed Z EZ Deo Rajat R St Peter Wendy L WL Kramlik Susan S Fischer Michael J MJ Navaneethan Sankar S Delafontaine Patrice P Jaar Bernard G BG Ojo Akinlolu A Makos Gail K GK Slaven Anne A Weir Matthew R MR Zhan Min M Fink Jeffrey C JC

Clinical journal of the American Society of Nephrology : CJASN 20170809 9

<h4>Background and objectives</h4>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.<h4>Design, setting, participants, & measurements</h4>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 (<i>n</i>=16,451 visi ...[more]

PMID: 28793999

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Project description:ImportanceQT-prolonging medications (QTPMs) are a reported risk factor for sudden cardiac death (SCD) when defined by consensus criteria that presume an arrhythmic cause. The effect of QTPM on autopsy-defined sudden arrhythmic death (SAD) is unknown.ObjectiveTo evaluate the association between QTPM and autopsy-defined SAD vs nonarrhythmic cause of sudden death.Design, setting, and participantsThis prospective countywide case-control study included World Health Organization-defined (presumed) SCD cases who underwent autopsy as part of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study (POST SCD) to determine arrhythmic or nonarrhythmic cause, and control deaths due to trauma (hereinafter referred to as trauma controls) in San Francisco County, California, from February 1, 2011, to March 1, 2014. Multivariate regression was used to evaluate the association of QTPM with the risk of presumed SCD, autopsy-defined SAD, and non-SAD compared with trauma controls. Medication exposure, determined by prescription lists and postmortem toxicologic findings, was used to calculate a summative QTPM exposure score (range, 0-20). Data were analyzed from September 1, 2018, to June 15, 2019.ExposureQT-prolonging medication exposure, as measured by QTPM score (1 indicated low; 2-4, moderate; and >4, high).Main outcomes and measuresDeath due to trauma, presumed SCD, and autopsy-defined non-SAD and SAD with no postmortem findings of extracardiac cause.ResultsA total of 629 patients (mean [SD] age, 61.4 [15.7] years; 439 men [69.8%]) were included, 525 with presumed SCDs and 104 traumatic death controls. Individuals with presumed SCDs had higher exposure and were more likely to be taking any QTPM (291 [55.4%] vs 28 [26.9%]; P?<?.001) than trauma controls. Use of QTPMs was associated with increased risk of presumed SCD in low (odds ratio [OR], 2.25 [95% CI, 1.03-4.96]; P?=?.04) and high (OR, 6.70 [95% CI, 1.47-30.67]; P?=?.01) exposure groups. After autopsy adjudication, use of QTPMs was associated with increased risk of non-SAD (low-risk OR, 2.88 [95% CI, 1.18-6.99; P?=?.02]; moderate-risk OR, 2.62 [95% CI, 1.20-5.73; P?=?.02]; and high-risk OR, 14.22 [95% CI, 2.91-69.30; P?=?.001]) but not SAD in all exposure groups. This association was attenuated by the exclusion of occult overdose non-SADs in the highest exposure group.Conclusions and relevanceThese findings confirm the association between QTPMs and presumed SCD; however, after autopsy, this risk was specific for nonarrhythmic causes of sudden death. Studies using consensus SCD criteria may overestimate the association of QTPMs with the risk of SAD.

Project description:There are contradictory reports regarding the effects of protease inhibitors on the ECG measures of QT and PR interval durations. The effect of interrupting use of protease inhibitors on QT and PR progression is also unknown.This analysis included 3719 participants from the Strategies for Management of Antiretroviral Therapy (SMART) study, of whom 1879 were randomized to receive intermittent antiretroviral therapy (ART) (drug conservation group), whereas the rest received these drugs continuously (viral suppression group). Linear regression analysis was used to compare four ritonavir-boosted protease inhibitor (protease inhibitor/r) regimens [saquinavir (SQV/r), lopinavir (LPV/r), atazanavir (ATV/r), and other protease inhibitor/r], and nonboosted protease inhibitor regimens with nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens for Bazett's (QTcB) and Fredericia's (QTcF) heart rate corrected QT and PR. Changes in QTcB, QTcF, and PR after 12 and 24 months of randomization were compared in the drug conservation group and viral suppression group.Average levels of QTcB, QTcF, and PR duration at entry were 415, 406, and 158 ms. At study entry, 49% of participants were taking an NNRTI (no protease inhibitor)-based regimen and 31% were prescribed a boosted protease inhibitor, the most common being LPV/r. After adjustment for baseline factors, QTcB and QTcF levels did not vary by boosted protease inhibitor group (P = 0.26 and P = 0.34, respectively). For those given any of the boosted protease inhibitors, QTcB was 1.5 ms lower than the NNRTI group (P = 0.04). Both boosted and nonboosted protease inhibitor-containing regimens were significantly associated (P < 0.01 for each) with longer PR intervals compared to the NNRTI group. After adjustment, the difference between boosted protease inhibitors and the NNRTI group was 5.11 ms (P < 0.01); for nonboosted protease inhibitors, this difference was 3.00 ms (P < 0.01). Following ART interruption, PR duration declined for both the boosted and nonboosted protease inhibitor groups and compared to the viral suppression group, significant changes in PR interval were observed 24 months after ART interruption of boosted protease inhibitors (P < 0.01).Different protease inhibitor-based regimens have a similar, minimal effect on QT compared to NNRTI-based regimens. All protease inhibitor-based regimens (boosted and nonboosted) were associated with prolongation of PR, and interruption of protease inhibitor regimens reduced the prolonged PR duration. Further research is needed to confirm the findings of this study and assess the clinical relevance of the differences.

Dataset Information

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

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Podcast

Publications

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

Similar Datasets

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