Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization.
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.
Graff
C
C
Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. cgraff@hst.aau.dk
Struijk
J J
JJ
Matz
J
J
Kanters
J K
JK
Andersen
M P
MP
Nielsen
J
J
Toft
E
E
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001372:Aza Compounds / Q000009:adverse effects*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography / Q000187:drug effects* / Q000706:statistics & numerical data*; D005260:Female; D024841:Fluoroquinolones; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000009:adverse effects*; D018570:Risk Assessment; D013015:Sotalol / Q000009:adverse effects*; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology; D055815:Young Adult
D000889:Anti-Arrhythmia Agents; D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D002317:Cardiovascular Agents; D024841:Fluoroquinolones; D011804:Quinolines; D013015:Sotalol; D000077266:Moxifloxacin