[Determination of duration of action of beta blockers with Holter-ECG registration]

Duration of Action of Betaadrenergic Blockers Determined with Holter-ECG in Healthy Volunteers In phase I, the duration of action of betaadrenergic blockers is usually determined from the reduction of exercise induced tachycardia. In this randomized placebocontrolled doubleblind trial, however, ambulatory 24-h heart rate monitoring was used in 12 healthy volunteers to evaluate the duration of action of the new cardioselective and vasodilating betaadrenergic blocker ridazolol (CAS413). After the control periods as well as after prospectively defined hours the following mean values of heart rate were obtained: Ridazolol: Control 65.2, 12 h 69.6, 16 h 64.9, 24 h 74.0 beasts/min, placebo: Control 64.8, 12 h 78.5, 16 h 69.7, 24 h 73.5 beats/min. Differences after 12 h were statistically significant and would have been significant after 16 h with more volunteers. Additional explorative analysis with adjustment of significance levels for multiple analysis resulted in significant effects from 2 to 14 h. It was not useful, however, to calculate the time of maximal and half-maximal effects because of the large individual variation. Holter-monitoring of spontaneous heart rate in volunteers provides a rapid orientation on the duration of action of betaadrenergic blockers. The method allows to fix prospectively reasonable times of evaluation in efficacy trials in patients with coronary artery disease.