Related Experiment Videos
Variability of heart rate correction methods for the QT interval
Mehul Desai1, Lang Li, Zeruesenay Desta
1Division of Clinical Pharmacology, Department of Medicine, Indiana University, Indianapolis, IN, USA, and Department of Cardiological Sciences, St George's Hospital Medical School, London, UK.
British Journal of Clinical Pharmacology
|June 20, 2003
Summary
This study compared three methods for correcting heart rate-corrected QT intervals (QTc) in patients taking haloperidol. A subject-specific method showed less dependence on heart rate, reducing over- or under-correction risks for QTc prolongation.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- The QT interval, corrected for heart rate (QTc), is crucial for assessing cardiac repolarization.
- Variability in QTc measurements can arise from different correction methods, impacting drug safety evaluations.
- Low-dose oral haloperidol's effect on QTc requires precise measurement techniques.
Purpose of the Study:
- To compare the variability of QTc measurements using Bazett's, Fridericia's, and a subject-specific correction method.
- To evaluate the impact of these methods on assessing QTc prolongation induced by low-dose oral haloperidol.
Main Methods:
- A randomized, double-blind, placebo-controlled, crossover trial involving 16 healthy subjects.
- Single oral doses of 10 mg haloperidol were administered.
- QTc was calculated using Bazett's, Fridericia's, and a novel subject-specific linear mixed modeling method.
Main Results:
- The subject-specific method yielded a correction factor (alpha) ranging from 0.23 to 0.38, differing from fixed factors of Bazett's (0.5) and Fridericia's (0.33).
- Subject-specific correction showed significantly lower mean slopes of QT vs. RR regression, indicating less heart rate dependency.
- All methods detected significant QTc prolongation with haloperidol compared to placebo, but the magnitude varied by correction method.
Conclusions:
- Haloperidol significantly prolongs QTc intervals, regardless of the correction method used.
- The subject-specific QTc correction method demonstrates reduced dependency on RR intervals, potentially minimizing over- or under-correction.
- Interindividual variability in QTc changes was significantly influenced by the chosen correction method.