Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization. / Graff, Claus; Struijk, Johannes J.; Matz, J; Kanters, Jørgen K.; Andersen, M P; Nielsen, J; Toft, E.
I: Clinical Pharmacology and Therapeutics, Bind 88, Nr. 1, 01.07.2010, s. 88-94.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization
AU - Graff, Claus
AU - Struijk, Johannes J.
AU - Matz, J
AU - Kanters, Jørgen K.
AU - Andersen, M P
AU - Nielsen, J
AU - Toft, E
PY - 2010/7/1
Y1 - 2010/7/1
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 400 mg moxifloxacin were compared with those from 21 subjects on 160 and 320 mg D,L-sotalol. T-wave morphology changes, as assessed by DeltaMCS, are larger after 320 mg D,L-sotalol than after 160 mg D,L-sotalol; and the changes associated with 160 mg D,L-sotalol are, in turn, larger than those associated with moxifloxacin and placebo. Covariate analyses of DeltaQTc and DeltaMCS 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 (DeltaMCS) 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 400 mg moxifloxacin were compared with those from 21 subjects on 160 and 320 mg D,L-sotalol. T-wave morphology changes, as assessed by DeltaMCS, are larger after 320 mg D,L-sotalol than after 160 mg D,L-sotalol; and the changes associated with 160 mg D,L-sotalol are, in turn, larger than those associated with moxifloxacin and placebo. Covariate analyses of DeltaQTc and DeltaMCS 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 (DeltaMCS) 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.
KW - Adolescent
KW - Adult
KW - Algorithms
KW - Anti-Arrhythmia Agents
KW - Anti-Bacterial Agents
KW - Aza Compounds
KW - Cardiovascular Agents
KW - Data Interpretation, Statistical
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
KW - Young Adult
U2 - 10.1038/clpt.2010.51
DO - 10.1038/clpt.2010.51
M3 - Journal article
C2 - 20485337
VL - 88
SP - 88
EP - 94
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 1
ER -
ID: 33910869