Dataset Information

Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death.

ABSTRACT:

Importance

QT-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.

Objective

To evaluate the association between QTPM and autopsy-defined SAD vs nonarrhythmic cause of sudden death.

Design, setting, and participants

This 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.

Exposure

QT-prolonging medication exposure, as measured by QTPM score (1 indicated low; 2-4, moderate; and >4, high).

Main outcomes and measures

Death due to trauma, presumed SCD, and autopsy-defined non-SAD and SAD with no postmortem findings of extracardiac cause.

Results

A 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?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.

SUBMITTER: Simpson TF

PROVIDER: S-EPMC7052791 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death.

Simpson Timothy F TF Salazar James W JW Vittinghoff Eric E Probert Joanne J Iwahashi Alan A Olgin Jeffrey E JE Ursell Phillip P Hart Amy A Moffatt Ellen E Tseng Zian H ZH

JAMA internal medicine 20200501 5

<h4>Importance</h4>QT-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.<h4>Objective</h4>To evaluate the association between QTPM and autopsy-defined SAD vs nonarrhythmic cause of sudden death.<h4>Design, setting, and participants</h4>This prospective countywide case-control study included World Health Organiza ...[more]

PMID: 32119028

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Project description:Rationale & objectiveTreatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin.Study designRetrospective observational cohort study using a new-user study design.Setting & populationAdult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017).ExposureInitiation of azithromycin (or levofloxacin/moxifloxacin) as compared to amoxicillin-based antibiotics (exposure). Serum-to-dialysate potassium gradient (effect modifier). Individual patients could contribute multiple study antibiotic treatment episodes to the analyses.OutcomesSudden cardiac death (14 days).Analytical approachInverse probability of treatment-weighted survival models to estimate HRs and robust 95% CIs.ResultsThe azithromycin versus amoxicillin-based antibiotic cohort included 89,379 unique patients with 113,516 azithromycin and 103,493 amoxicillin-based treatment episodes. Azithromycin versus amoxicillin-based antibiotic treatment was associated with a higher risk of sudden cardiac death overall, HR, 1.68; 95% CI, 1.31-2.16. The risk was numerically higher when the baseline serum-to-dialysate potassium gradient was ≥3 mEq/L compared with <3 mEq/L (HR, 2.22; 95% CI, 1.46-3.40 vs HR, 1.43; 95% CI. 1.04-1.96, P interaction = 0.07). Analogous analyses in a respiratory fluoroquinolone (levofloxacin/moxifloxacin) versus amoxicillin-based antibiotic cohort with 79,449 unique patients and 65,959 respiratory fluoroquinolone and 103,776 amoxicillin-based treatment episodes yielded similar results.LimitationsResidual confounding.ConclusionsAlthough treatment with azithromycin and, separately, respiratory fluoroquinolones were each associated with a heightened risk of sudden cardiac death, this risk was augmented in the setting of larger serum-to-dialysate potassium gradients. Minimizing the potassium gradient may be an approach to reduce the cardiac risk of these antibiotics.

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Dataset Information

Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death.

Importance

Objective

Design, setting, and participants

Exposure

Main outcomes and measures

Results

Publications

Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death.

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