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Investigating the Additive Interaction of QT-Prolonging Drugs in Older People Using Claims Data

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Abstract

Introduction

Drugs that potentially prolong the QT interval carry the risk of life-threatening Torsades de pointes (TdP) ventricular arrhythmia.

Objective

The objective of this study was to investigate the potential additive risk for ventricular arrhythmia with concomitant prescriptions of QT-prolonging drugs.

Methods

Claims data for persons aged ≥65 years between 2010 and 2012 in Germany were analyzed and all cases hospitalized for ventricular arrhythmia were selected. In a case-crossover analysis, exposure with QT-prolonging drugs according to the Arizona Center for Education and Research on Therapeutics (AZCERT) classification of ‘known,’ ‘conditional,’ and ‘possible’ TdP risk was determined in respective event and control windows preceding hospitalization. Conditional logistic regression was applied to derive odds ratios (ORs).

Results

Among 6,849,622 health-insured persons, we identified 2572 patients newly hospitalized for ventricular arrhythmia. Drugs with ‘known’ risk were more frequently prescribed in the event window than in the control window (309 vs. 239; P < 0.001). The number of drugs with an attributed ‘known’ risk of TdP was significantly associated with hospitalization for ventricular arrhythmia (OR: 2.22; 95% confidence interval [1.51–3.25]; P < 0.001), while increased risk estimates were also obtained upon categorization into one and two or more drugs compared with no drugs for the combined group of drug with ‘known’ (1.52 [1.16–2.00]) and ‘conditional’ risk (2.20 [1.42–3.41]). Pairwise comparisons and trend tests based on these classification categories could not demonstrate a significantly increased risk of two or more drugs compared with one drug.

Conclusion

Beyond suitable single-drug classifications for QT-associated risk estimation, the situation when there is co-prescription of several drugs appears to be complex and may not be extrapolated to all possible multi-drug combinations.

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Acknowledgements

The authors would like to thank Andreas Wirtherle for support using the database of the AiDKlinik ® drug information system.

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Andreas D. Meid, Anna von Medem, Hanna M. Seidling, Renate Quinzler & Walter E. Haefeli

  2. Cooperation Unit Clinical Pharmacy, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Anna von Medem & Hanna M. Seidling

  3. Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Dirk Heider & Hans-Helmut König

  4. Wissenschaftliches Institut der AOK (WIdO), Rosenthaler Straße 31, 10178, Berlin, Germany

    Jürgen-Bernhard Adler & Christian Günster

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  1. Andreas D. Meid
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Correspondence to Walter E. Haefeli.

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Funding

The German Ministry of Education and Research (“Bundesministerium für Bildung und Forschung” [BMBF]) supported the conduct of the study under Grant Numbers 01GY1329B and 01GY1320B.

Conflicts of interest

Andreas D. Meid, Anna von Medem, Dirk Heider, Jürgen-Bernhard Adler, Christian Günster, Hanna M. Seidling, Renate Quinzler, Hans-Helmut König, and Walter E. Haefeli have no conflicts of interest that are directly relevant to the content of this study.

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In Germany by law, retrospective claims analyses do not require ethics committee approval.

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Meid, A.D., von Medem, A., Heider, D. et al. Investigating the Additive Interaction of QT-Prolonging Drugs in Older People Using Claims Data. Drug Saf 40, 133–144 (2017). https://doi.org/10.1007/s40264-016-0477-y

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