Lack of anti-ischemic efficacy of the potassium channel opener bimakalim in patients with stable angina pectoris.
Aim of the study was to evaluate anti-ischemic, hemodynamic and neurohumoral effects of bimakalim, a novel selective K(+)-channel opener, in patients with stable angina pectoris and reproducible ST-segment depression.


RESULTS
86 patients with angiographic signs of CAD were involved in two randomised, placebo-controlled, double-blind trials with single high (0.1, 0.3 or 0.6 mg) and low (0.025 or 0.05 mg) doses of oral bimakalim. The anti-anginal efficacy was evaluated by analysis of ST-segment depression within exercise or RV pacing. A parallel assessment of hemodynamic parameters was done by means of right-heart catheterization. Given in high doses, bimakalim acted as a potent vasodilator and decreased SBP by 15 mm Hg. This was associated with a reflex activation of sympathetic nervous system resulting in an increase in heart rate by 25 /min, a 14% rise of myocardial oxygen consumption and a 63% elevation of noradrenaline plasma level. Low doses of bimakalim had no significant effect on hemodynamics and oxygen consumption. In exercise-induced angina pectoris, administration of bimakalim was neither associated with attenuation of ST-segment depression nor resulted in prolongation of time to 0.1 mV ST-segment depression.


CONCLUSIONS
The results of the present study suggest that bimakalim has a dose-dependent vasodilatatory activity but exerts no anti-ischemic benefits in patients with exercise-induced angina pectoris due to coronary artery disease.
Burian
Maria
M
Department of Clinical Pharmacology, University Clinic of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany. burian@em.uni-frankfurt.de
Piske
Michael
M
Petkovic
Draga
D
Mitrovic
Veselin
V
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D015221:Potassium Channels / Q000819:agonists*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D001578:Benzopyrans; D004095:Dihydropyridines; D015221:Potassium Channels; C061050:bimakalim