title: Antianginal and anti-ischaemic efficacy of tedisamil, a potassium channel blocker.
abstract: OBJECTIVE
  To determine the efficacy and safety of the potassium channel blocker tedisamil versus placebo in the treatment of patients with stable angina.
  
  
  METHODS
  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.
  
  
  METHODS
  Primary efficacy 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 effect 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 effects 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 effective antianginal and anti-ischaemic agent. At doses above 100 mg twice daily its main side effect, diarrhoea, becomes pronounced; therefore the 50-100 mg twice daily regimen appears to be appropriate.
authors.affiliation: Royal Brompton and Harefield NHS Trust, Sydney Street, London SW3 6NP, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Fox
authors.forename: J R
authors.initials: JR
authors.lastname: Henderson
authors.forename: J C
authors.initials: JC
authors.lastname: Kaski
authors.forename: A
authors.initials: A
authors.lastname: Sachse
authors.forename: L
authors.initials: L
authors.lastname: Kuester
authors.forename: S
authors.initials: S
authors.lastname: Wonnacott
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002316:Cardiotonic Agents; D003521:Cyclopropanes; C059921:tedisamil