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Comparison of Two Highly Automated ECG Algorithms for Detection of Drug‐Induced Cardiac Ion Channel Block
Author(s) -
Brockway Marina,
Fossa Anthony A.,
Mason Jay W.
Publication year - 2018
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.934
Subject(s) - algorithm , confidence interval , dofetilide , medicine , ranolazine , crossover study , food and drug administration , verapamil , statistics , mathematics , qt interval , pharmacology , alternative medicine , pathology , calcium , placebo
US Food and Drug Administration (FDA) investigators recently demonstrated in a crossover study that early (J‐T peak c) and late (T peak –T end ) repolarization duration can differentiate selective potassium block with a high arrhythmia risk from multichannel block with lower risk in subjects receiving dofetilide, verapamil, quinidine, or ranolazine. The purpose of this study was to determine if the findings by the FDA using their published software algorithm could be corroborated using an alternative software algorithm for the same metrics and to determine if methodological differences resulted in clinically meaningful differences in interpretation. Exposure–response relationships computed with linear mixed effects models and mean maximal effects on ECG intervals measured by the two algorithms were similar, corroborating the FDA findings, but with some differences in the modeled slopes and magnitude of changes. The alternative software resulted in an average 25% reduction in the 95% confidence intervals of the mixed effects models with generally lower Akaike Information Criterion values.