Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization

Claus Graff; Johannes J. Struijk; J Matz; Jørgen K. Kanters; M P Andersen; J Nielsen; E Toft

doi:10.1038/clpt.2010.51

Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization

Claus Graff, Johannes J. Struijk, J Matz, Jørgen K. Kanters, M P Andersen, J Nielsen, E Toft

Physiology of circulation, kidney and lung

22 Citationer (Scopus)

Abstract

This study adds the dimension of a T-wave morphology composite score (MCS) to the QTc interval-based evaluation of drugs that affect cardiac repolarization. Electrocardiographic recordings from 62 subjects on placebo and 400mg moxifloxacin were compared with those from 21 subjects on 160 and 320mg D,L-sotalol. T-wave morphology changes, as assessed by ΔMCS, are larger after 320mg D,L-sotalol than after 160mg D,L-sotalol; and the changes associated with 160mg D,L-sotalol are, in turn, larger than those associated with moxifloxacin and placebo. Covariate analyses of ΔQTc and ΔMCS showed that changes in T-wave morphology are a significant effect of D,L-sotalol. By contrast, moxifloxacin was found to have no significant effect on T-wave morphology (ΔMCS) at any given change in QTc. This study offers new insights into the repolarization behavior of a drug associated with low cardiac risk vs. one associated with a high risk and describes the added benefits of a T-wave MCS as a covariate to the assessment of the QTc interval.

Originalsprog	Engelsk
Tidsskrift	Clinical Pharmacology and Therapeutics
Vol/bind	88
Udgave nummer	1
Sider (fra-til)	88-94
Antal sider	7
ISSN	0009-9236
DOI	https://doi.org/10.1038/clpt.2010.51
Status	Udgivet - 24 jul. 2010

Adgang til dokumentet

10.1038/clpt.2010.51

Citationsformater

Graff, C., Struijk, J. J., Matz, J., Kanters, J. K., Andersen, M. P., Nielsen, J., & Toft, E. (2010). Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization. Clinical Pharmacology and Therapeutics, 88(1), 88-94. https://doi.org/10.1038/clpt.2010.51

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abstract = "This study adds the dimension of a T-wave morphology composite score (MCS) to the QTc interval-based evaluation of drugs that affect cardiac repolarization. Electrocardiographic recordings from 62 subjects on placebo and 400mg moxifloxacin were compared with those from 21 subjects on 160 and 320mg D,L-sotalol. T-wave morphology changes, as assessed by ΔMCS, are larger after 320mg D,L-sotalol than after 160mg D,L-sotalol; and the changes associated with 160mg D,L-sotalol are, in turn, larger than those associated with moxifloxacin and placebo. Covariate analyses of ΔQTc and ΔMCS showed that changes in T-wave morphology are a significant effect of D,L-sotalol. By contrast, moxifloxacin was found to have no significant effect on T-wave morphology (ΔMCS) at any given change in QTc. This study offers new insights into the repolarization behavior of a drug associated with low cardiac risk vs. one associated with a high risk and describes the added benefits of a T-wave MCS as a covariate to the assessment of the QTc interval.",

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AU - Andersen, M P

AU - Nielsen, J

AU - Toft, E

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N2 - This study adds the dimension of a T-wave morphology composite score (MCS) to the QTc interval-based evaluation of drugs that affect cardiac repolarization. Electrocardiographic recordings from 62 subjects on placebo and 400mg moxifloxacin were compared with those from 21 subjects on 160 and 320mg D,L-sotalol. T-wave morphology changes, as assessed by ΔMCS, are larger after 320mg D,L-sotalol than after 160mg D,L-sotalol; and the changes associated with 160mg D,L-sotalol are, in turn, larger than those associated with moxifloxacin and placebo. Covariate analyses of ΔQTc and ΔMCS showed that changes in T-wave morphology are a significant effect of D,L-sotalol. By contrast, moxifloxacin was found to have no significant effect on T-wave morphology (ΔMCS) at any given change in QTc. This study offers new insights into the repolarization behavior of a drug associated with low cardiac risk vs. one associated with a high risk and describes the added benefits of a T-wave MCS as a covariate to the assessment of the QTc interval.

AB - This study adds the dimension of a T-wave morphology composite score (MCS) to the QTc interval-based evaluation of drugs that affect cardiac repolarization. Electrocardiographic recordings from 62 subjects on placebo and 400mg moxifloxacin were compared with those from 21 subjects on 160 and 320mg D,L-sotalol. T-wave morphology changes, as assessed by ΔMCS, are larger after 320mg D,L-sotalol than after 160mg D,L-sotalol; and the changes associated with 160mg D,L-sotalol are, in turn, larger than those associated with moxifloxacin and placebo. Covariate analyses of ΔQTc and ΔMCS showed that changes in T-wave morphology are a significant effect of D,L-sotalol. By contrast, moxifloxacin was found to have no significant effect on T-wave morphology (ΔMCS) at any given change in QTc. This study offers new insights into the repolarization behavior of a drug associated with low cardiac risk vs. one associated with a high risk and describes the added benefits of a T-wave MCS as a covariate to the assessment of the QTc interval.

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KW - Electrocardiography

KW - Female

KW - Heart

KW - Humans

KW - Male

KW - Middle Aged

KW - Pharmaceutical Preparations

KW - Quinolines

KW - Risk Assessment

KW - Sotalol

KW - Torsades de Pointes

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ER -

Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization

Abstract

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