Antianginal and anti-ischaemic efficacy of tedisamil, a potassium channel blocker

Abstract

Objective-To determine the eYcacy and safety of the potassium channel blocker tedisamil versus placebo in the treatment of patients with stable angina. Design-Prospective, double blind, placebo controlled study. 203 patients first completed a seven day placebo run in. They were then randomised to receive 50 mg, 100 mg or 150 mg tedisamil twice daily, or placebo. Treadmill exercise testing was carried out at baseline and after 14 days of double blind treatment. Main outcome measures-Primary eYcacy parameters were an increase in total exercise duration and a reduction of the sum of ST segment depression using six ECG leads at maximum workload at trough (12 hours after last medication). Secondary aims included increase in exercise time to onset of 0.1 mV ST segment depression, increase in exercise time to onset of any anginal pain, and reduction in ST segment depression in any of the six specified leads at maximum workload. These were all at trough. The same parameters were also assessed at peak concentrations (two hours after administration). Overall attacks of angina and the use of short acting nitrates were assessed from patient diaries. Results-Tedisamil led to a dose dependent prolongation of exercise duration (significant at all concentrations), an eVect that was greater at peak than at trough. Treatment also led to a significant dose dependent reduction in the sum of ST segment depression at both trough and peak concentrations. Tedisamil also decreased (in a dose dependent way) the frequency of anginal attacks and the consumption of short acting nitrates, an improvement that became significant for all doses in the second treatment week. Adverse events with tedisamil were few. There was a pronounced rise in the incidence of diarrhoea with the 150 mg twice daily regimen. Bradycardic eVects and increases in QT interval were dose dependent, but were no more evident at exercise than at rest. Conclusions-Tedisamil, at doses of 50-100 mg twice daily, was found to be an eVective antianginal and anti-ischaemic agent. At doses above 100 mg twice daily its main side eVect, diarrhoea, becomes pronounced; therefore the 50-100 mg twice daily regimen appears to be appropriate.

Effects of Tedisamil on Cardiovascular Tissues Isolated from Normoand Hypertensive Rats

“…Tedisamil is a bradycardic agent that is in clinical trial for angina (2,3) and heart failure (4). Inhibition of the transient outward potassium current (Ito) of human atrial myocytes (5) probably underlies the bradycardic effect of tedisamil.…”

New antiarrhythmic agents for atrial fibrillation

“…Another major advantage is the lack of negative inotropic action. Though tedisamil has been shown to be effective in a dose-dependent fashion in increasing angina threshold and reducing the frequency of angina, it also exhibits reverse dose-dependence, thus limiting its efficacy with exercise and rendering β-blockers superior [50]. In animal studies, tedisamil has been shown to be effective in preventing and reversing ventricular arrhythmia in the ischemic setting [51].…”

Drug Therapy in Brugada Syndrome

“…Tedisamil (KC8857) is a drug tested in ischaemic heart disease due to its bradycardic effect. In coronary artery disease, tedisamil has no effect on inotropism and increases the threshold for angina [65,66]. Its antiarrhythmic properties includes dosedependent lengthening of the ventricular relative and effective refractory periods and prevention of electricallyinduced VF in experimental models of coronary artery occlusion [67].…”