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Development of a risk score for QTc-prolongation: the RISQ-PATH study

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Abstract

Background More than 170 drugs are linked with QTc-prolongation, which in extreme cases can lead to Torsade de Pointes. Monitoring of this potential side effect is an important challenge in clinical practice. Objective To investigate the risk of QTc-prolongation in hospital patients who started a QTc-prolonging drug, and to develop a risk score to identify patients at high/low risk for QTc-prolongation. Setting University Hospitals Leuven, Belgium. Method All patients starting with haloperidol or a QTc-prolonging antibiotic/antimycotic were eligible for this observational study. Twelve-lead electrocardiograms were recorded at baseline and follow-up (steady state). Demographic, medical and drug data were collected. The obtained data were used to calculate the performance characteristics of a preliminary risk score (RISQ-PATH score), based on a systematic review of risk factors. ROC analysis determined a score of <10 points as a low risk for QTc-prolongation. Main outcome measure QTc-interval in a baseline and follow-up electrocardiogram. Results 178 patients (46.6% female; mean age 69 ± 14 years) were included (levofloxacin: N = 80; haloperidol: N = 41; fluconazole: N = 41). Overall, no significant difference between the mean QTc-values at baseline (425.7 ± 31.7 ms) and follow-up (428.0 ± 30.7 ms) was found (p = 0.328). However, 26 patients (14.6%) did develop a prolonged QTc-interval (≥450(♂)/470(♀) ms) of whom 25 with a RISQ-PATH score ≥10. This score had a sensitivity of 96.2% (95% CI 78.4–99.8%) and a negative predictive value of 98.0% (95% CI 88.2–99.9%). Conclusion This RISQ-PATH score is able to rule out low-risk patients with a negative predictive value of 98.0% and is promising to exclude patients from further follow-up when starting QTc-prolonging drugs.

Clinicaltrials.gov Registration Number: NCT02068170.

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Acknowledgements

We want to thank the University Hospitals Leuven, especially the treating physicians, nursing staff and IT service.

Funding

Ph.D.-student EV is supported by funding of the Belgian government agency for Innovation by Science and Technology (IWT). RW is supported as a clinical researcher by the Fund for Scientific Research Flanders. IS is supported by the Clinical Research Fund of the University Hospitals Leuven.

Conflicts of interest

None declared.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical and Pharmacological Sciences, Clinical Pharmacology and Pharmacotherapy, KU Leuven, Herestraat 49, Box 521, 3000, Leuven, Belgium

    Eline Vandael, Isabel Spriet & Veerle Foulon

  2. Department of Cardiovascular Sciences, KU Leuven, 3000, Leuven, Belgium

    Bert Vandenberk & Rik Willems

  3. Cardiology, University Hospitals Leuven, 3000, Leuven, Belgium

    Bert Vandenberk & Rik Willems

  4. Department of Neurosciences, KU Leuven, 3000, Leuven, Belgium

    Joris Vandenberghe

  5. Psychiatry, University Hospitals Leuven, 3000, Leuven, Belgium

    Joris Vandenberghe

  6. Pharmacy Department, University Hospitals Leuven, 3000, Leuven, Belgium

    Isabel Spriet

Authors
  1. Eline Vandael
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  2. Bert Vandenberk
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  3. Joris Vandenberghe
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  4. Isabel Spriet
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  5. Rik Willems
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  6. Veerle Foulon
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Correspondence to Eline Vandael.

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Vandael, E., Vandenberk, B., Vandenberghe, J. et al. Development of a risk score for QTc-prolongation: the RISQ-PATH study. Int J Clin Pharm 39, 424–432 (2017). https://doi.org/10.1007/s11096-017-0446-2

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  • DOI: https://doi.org/10.1007/s11096-017-0446-2

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