[Effects of the K(+) channel blocker tedisamil on hemodynamics, myocardial ischemia and neurohumoral systems in patients with stable angina pectoris. A comparison with the beta blocker atenolol].
BACKGROUND
Clinical drawbacks of beta-blocker treatment in stable angina have motivated researchers to provide alternative heart rat lowering agents, such as tedisamil which additionally exerts anti-ischemic and antiarrhythmic effects by blockade of cellular repolarizing K(+) currents.


RESULTS
48 patients with stable angina pectoris were investigated (double-blind, randomized, parallel grouped) comparing the hemodynamic, anti-ischemic, metabolic and neurohumoral effects of tedisamil 100 mg b.i.d and atenolol 50 mg b.i.d. after a single dose and over 6 days of treatment. Tedisamil and atenolol produced a decrease in heart rate both at rest (day 1: -13.6 vs -15.4 bpm; p > 0.05; day 6: -14.8 vs -22.2 bpm; resp.; p > 0.05) and exercise (day 1: -9.1 vs -18.3 bpm; p = 0. 001; day 6: -12.0 vs -24.8 bpm, resp.; p = 0.001), while anginal threshold increased. Cardiac output decreased with tedisamil and atenolol at rest (day 1: -1.01 vs -1.19 l/min; p > 0.05; day 6: -0. 86 vs -1.10 l/min, resp.; p > 0.05) and exercise (day 1: -0.82 vs -1. 28 l/min; p > 0.05; day 6: -0.65 vs -2.68 l/min, resp.; p = 0.03), while stroke volume remained unchanged. Right atrial pressure changed during exercise only: It decreased with tedisamil (-1.7 mm Hg) and increased with atenolol (+3.7 mm Hg). Mean pulmonary capillary wedge pressures decreased at rest (-0.5 mm Hg) and exercise (-6.9 mm Hg) in the tedisamil group, but tended to increase with atenolol on day 6 (rest: +1.7; exercise: +3.7 mm Hg) (p = 0.03). Arterial pressure decreased under atenolol treatment only. Exercise-induced plasma norepinephrine levels were reduced by tedisamil (-93 pg/ml) but elevated by atenolol (+172 pg/ml) (p = 0. 001). As compared to atenolol, tedisamil produced a significant prolongation of QT (c) interval (+31 vs -8 ms) (p = 0.002) at initial values of 0.408 +/- 0.018 s with PQ and QRS remaining unaltered.


CONCLUSIONS
In the present study, tedisamil (100 mg b.i.d. ) generated favorable hemodynamic, neurohumoral and anti-ischemic effects in patients with stable angina pectoris. The anti-ischemic efficacy of tedisamil, as measured by ST segment depression and angina threshold, is comparable to that of atenolol (50 mg b.i.d.).
Mitrovic
V
V
Kerckhoff-Klinik GmbH, Benekestr. 2-8, D-61231 Bad Nauheim. Veselin.Mitrovic@kerckhoff.med.uni-giessen.de
Miskovic
A
A
Straub
M
M
Beckmann
K
K
Thormann
J
J
Pitschner
H
H
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000787:Angina Pectoris / Q000188:drug therapy*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001262:Atenolol / Q000009:adverse effects / Q000627:therapeutic use*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects*; D003521:Cyclopropanes / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D026902:Potassium Channel Blockers; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003521:Cyclopropanes; D026902:Potassium Channel Blockers; D001262:Atenolol; C059921:tedisamil; D009638:Norepinephrine