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Contrasting Time‐ and Rate‐Based Approaches for the Assessment of Drug‐Induced QT Changes
Author(s) -
Extramiana Fabrice,
Badilini Fabio,
Sarapa Nenad,
Leenhardt Antoine,
MaisonBlanche Pierre
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007302953
Subject(s) - sotalol , qt interval , placebo , qrs complex , medicine , heart rate , drug , cardiology , electrocardiography , anesthesia , pharmacology , atrial fibrillation , alternative medicine , pathology , blood pressure
The authors aim to highlight the pitfalls of different validated methods used for the assessment of drugs' effect on QT duration. Digital 12‐lead Holter electrocardiograms were recorded at baseline and after a single dose of sotalol in 39 healthy subjects (age = 27.4 ± 8.0 years). Using both time‐ and rate‐based approaches, the authors obtained averaged QRS‐T complexes every minute (“time bins”) and at different RR intervals (“rate bins”). Time bins were corrected for heart rate using a subject‐specific approach. The individual α coefficients increased from placebo (0.309 ± 0.052) to sotalol (0.454 ± 0.136), P < .0001. When the placebo individual α coefficients were applied to correct the QT interval on sotalol, the changes were >5 ms smaller than those obtained using the ON drug α coefficients. The “rate”‐averaging process leads to a complete loss of the time course of drug effect. In conclusion, the individual correction formula calculated from the placebo condition cannot always be used for QT correction on the drug.