title: Development of a risk score for QTc-prolongation: the RISQ-PATH study.
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.
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Clinical Pharmacology and Pharmacotherapy, KU Leuven, Herestraat 49, Box 521, 3000, Leuven, Belgium. Eline.Vandael@kuleuven.be.
authors.forename: Eline
authors.identifier: http://orcid.org/0000-0001-7003-7448
authors.initials: E
authors.lastname: Vandael
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, 3000, Leuven, Belgium.|Cardiology, University Hospitals Leuven, 3000, Leuven, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Vandenberk
authors.affiliation: Department of Neurosciences, KU Leuven, 3000, Leuven, Belgium.|Psychiatry, University Hospitals Leuven, 3000, Leuven, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: Vandenberghe
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Clinical Pharmacology and Pharmacotherapy, KU Leuven, Herestraat 49, Box 521, 3000, Leuven, Belgium.|Pharmacy Department, University Hospitals Leuven, 3000, Leuven, Belgium.
authors.forename: Isabel
authors.initials: I
authors.lastname: Spriet
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, 3000, Leuven, Belgium.|Cardiology, University Hospitals Leuven, 3000, Leuven, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Willems
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Clinical Pharmacology and Pharmacotherapy, KU Leuven, Herestraat 49, Box 521, 3000, Leuven, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Foulon
mesh_terms: D000368:Aged; D005260:Female; D015725:Fluconazole / Q000009:adverse effects*; D006220:Haloperidol / Q000009:adverse effects*; D006801:Humans; D064704:Levofloxacin / Q000009:adverse effects*; D008133:Long QT Syndrome / Q000139:chemically induced / Q000175:diagnosis*; D008297:Male; D015233:Models, Statistical; D011237:Predictive Value of Tests; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D064704:Levofloxacin; D015725:Fluconazole; D006220:Haloperidol
keywords: Observational study; QTc-prolongation; Risk management; Risk score