ASSESSMENT OF REVERSE USE-DEPENDENT BLOCKING ACTIONS OF CLASS-III ANTIARRHYTHMIC DRUGS BY 24-HOUR HOLTER ELECTROCARDIOGRAPHY

Objectives. This clinical study was designed to compare rate-dependent effects of class III agents on QT prolongation. Background. Clinical data that compare the electrophysiologic differences among class III a gents with different selectivity for potassium channels are still lack ing. Methods. QT intervals were measured over a wide range of precedin g RR intervals during sinus rhythm by 24-h Holter electrocardiography before and after oral administration of four class III agents: E4031, dofetilide, MS551 and d-sotalol, Rate-dependent changes in the QT inte rval were assessed by the slope of the linear regression line estimati ng the QT-root RR relation. Results. All agents significantly increase d the mean slope: E4031 increased the mean [+/- SD] value from 0.32 +/ - 0.05 to 0.42 +/- 0.13 (p < 0.01), dofetilide from 0.32 +/- 0.03 to 0 .50 +/- 0.12 (p < 0.03), MS551 from 0.35 +/- 0.06 to 0.45 +/- 0.10 (p < 0.02) and d-sotalol from 0.31 +/- 0.05 to 0.33 +/- 0.03 (p < 0.05), However, in those patients given either E4031, dofetilide or MS551, th e degree of QT prolongation was smaller at shorter root RR intervals a nd was better preserved at shorter root RR intervals by d-sotalol, wit h a smaller increase in slope (p < 0.02 vs, dofetilide and MS551). Con clusions. On ambulatory electrocardiography, reverse use dependence in QT prolongation was least prominent with d-sotalol among the four stu dy drugs, In the range of physiologic heart rates, class III agents co uld manifest different profiles of rate dependence in their QT-prolong ing effect.