Abstract

BackgroundQTc-prolongation is an independent risk factor for developing life-threatening arrhythmias. Risk management of drug-induced QTc-prolongation is complex and digital support tools could be of assistance. Bindraban et al. and Berger et al. developed two algorithms to identify patients at risk for QTc-prolongation. ObjectiveThe main aim of this study was to compare the performances of these algorithms for managing QTc-prolonging drug-drug interactions (QT-DDIs). Materials and MethodsA retrospective data analysis was performed. A dataset was created from QT-DDI alerts generated for in- and outpatients at a general teaching hospital between November 2016 and March 2018. ECGs recorded within 7 days of the QT-DDI alert were collected. Main outcomes were the performance characteristics of both algorithms. QTc-intervals of > 500 ms on the first ECG after the alert were taken as outcome parameter, to which the performances were compared. Secondary outcome was the distribution of risk scores in the study cohort. ResultsIn total, 10,870 QT-DDI alerts of 4987 patients were included. ECGs were recorded in 26.2 % of the QT-DDI alerts. Application of the algorithms resulted in area under the ROC-curves of 0.81 (95 % CI 0.79–0.84) for Bindraban et al. and 0.73 (0.70–0.75) for Berger et al. Cut-off values of ≥ 3 and ≥ 6 led to sensitivities of 85.7 % and 89.1 %, and specificities of 60.8 % and 44.3 % respectively. ConclusionsBoth algorithms showed good discriminative abilities to identify patients at risk for QTc-prolongation when using ≥ 2 QTc-prolonging drugs. Implementation of digital algorithms in clinical decision support systems could support the risk management of QT-DDIs.

Highlights

  • Several commonly used drugs prolong the QT or heart-rate corrected QT (QTc) interval

  • A prolonged QTc-interval is an independent risk factor for Torsade de Pointes (TdP), a potentially life-threatening arrhythmia that may result in ventricular fibrillation or sudden car­ diac death (SCD) [1,2]

  • As the risk factors of pa­ tients could change over time, we evaluated each QTcprolonging drug-drug interactions (QT-DDIs) alert separate from the others

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Summary

Introduction

Several commonly used drugs prolong the QT or heart-rate corrected QT (QTc) interval. QTc-prolonging drugs should not be prescribed to patients who are likely to develop QTc-intervals above this threshold [6, 7]. Heemskerk et al showed that increasing numbers of risk factors for QTc-prolongation have an increasing effect on the QTc-interval [9]. Bindraban et al and Berger et al developed two algorithms to identify patients at risk for QTc-prolongation. Objective: The main aim of this study was to compare the performances of these algorithms for managing QTcprolonging drug-drug interactions (QT-DDIs). QTc-intervals of > 500 ms on the first ECG after the alert were taken as outcome parameter, to which the performances were compared. Conclusions: Both algorithms showed good discriminative abilities to identify patients at risk for QTcprolongation when using ≥ 2 QTc-prolonging drugs. Implementation of digital algorithms in clinical decision support systems could support the risk management of QT-DDIs

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