Anti-angina effect of the calcium antagonist bepridil in stable angina pectoris
Schneider, W.; Mehlhorn, C.; Kaltenbach, M.; Bussmann, W.D.
Zeitschrift für Kardiologie 74(6): 341-347
1985
ISSN/ISBN: 0300-5860 PMID: 3895761 Document Number: 247797
Twelve patients with angiographically proven coronary artery disease and stable, exercise-induced angina pectoris were treated in a randomized sequence with placebo (PL) and bepridil tablets in maintenance doses of 200 mg, 400 mg and 600 mg per day for 1 wk each, according to a double blind-protocol with intra-individual cross-over. The 4 treatment phases were separated by 2-wk wash-out periods (placebo). On day 7 of each treatment phase and at the end of each wash-out period heart rate and blood pressure were measured 2 and 5 h after drug intake and exercise stress testing was performed. The mean plasma concentrations at the end of the 1-wk treatment periods 2 h after drug intake were: 375 .+-. 202 ng/ml (200 mg/day), 844 .+-. 273 ng/ml (400 ng/day) and 1378 .+-. 538 ng/ml (600 mg/day). Systolic blood pressure was not influenced by either bepridil dose. Diastolic blood pressure was slightly reduced (-6%) after 600 mg bepridil/day (P < 0.05). While heart rate at rest in the upright position tended to lower values with regard to bepridil dosages, it was significantly lowered at the end of stress testing (2 h/5 h): 400 mg: -7% (P < 0.05)/-15% (P < 0.05); 600 mg: -11% (P < 0.001)/-10% (P < 0.05). Myocardial ischemia (sum of ST-segment depressions) was improved in a dose-dependent manner (2 h/5 h): 200 mg: -21% (P < 0.05)/-31% (n.s.); 400 mg: -27% (n.s.)/-31% (P < 0.01); 600 mg: -56% (P < 0.001)/-55% (P < 0.01). The time of onset of angina during stress testing was prolonged after bepridil therapy with a better efficacy of the higher doses (2 h/5 h): 200 mg: +33% (P < 0.01)/+31% (P < 0.05); 400 mg: +58% (P < 0.001)/+75% (P < 0.01); 600 mg; +82% (P < 0.01)/ +62% (P < 0.01). The QTc-interval at rest (2 h/5 h) was prolonged to 446 .+-. 37 ms (P < 0.01)/442 .+-. 50 ms (n.s.) after a 1-wk therapy with 600 mg bepridil. At the end of stress testing mean QTc interval showed a considerable increase to 485 .+-. 56 ms (P < 0.05) (2 h) and 497 .+-. 44 ms (P < 0.001) after the highest bepridil dose (600 mg).