EFFECTS OF TEDISAMIL, ATENOLOL AND THEIR COMBINATION ON HEART AND RATE-DEPENDENT QT INTERVAL IN HEALTHY-VOLUNTEERS

Aims Tedisamil is a new blocker of K+ currents in cardiac tissues, exe rts bradycardic effects and has shown clinical efficacy in angina pect oris. Theoretically, when coadministered with a beta-adrenoceptor bloc ker the tedisamil combination could induce dangerous bradycardia and Q T interval prolongation. Therefore, the aim of this study was to evalu ate the effects of tedisamil and atenolol alone and in combination, on heart rate and QT interval duration at rest and during exercise tests . Methods The effects of tedisamil (100 mg twice daily) and atenolol ( 50 mg twice daily) on heart rate and QT interval duration were analyse d in a three-period crossover study in healthy male volunteers. Result s This study showed that tedisamil exerted a significant (P < 0.05) br adycardic action at rest (-10 beats min(-1); 95% CI: -6 to -15 beats m in(-1)) similar to atenolol (-14 beats min(-1); -11 to -17) and drug c ombination (-9 beats min(-1); -6 to -12). During exercise, at the high est comparable workload, heart rate did not decrease significantly wit h tedisamil but decreased significantly with atenolol (-42 beats min(- 1); -37 to -47) and combination (-47 beats min(-1); -41 to 52). Atenol ol did not modify QT interval duration. Tedisamil alone and in combina tion with atenolol increased QT interval duration by 12% (95% CI: 7 to 17%) and 12% (8 to 16) respectively at RR = 1000ms, but not at RR < 7 00ms (combination). Tedisamil alone and in combination induced a rever se rate-dependent QT interval prolongation. Conclusions These results indicate that the combination of tedisamil and atenolol is not associa ted with excessive bradycardia or excessive QT interval prolongation i n healthy subjects.