The contractility enhancing effect of the calcium sensitiser levosimendan is not attenuated by carvedilol in healthy subjects

Objective: It was assessed whether the contractility enhancing effect of the calcium sensitiser levosimendan is altered by carvedilol. Methods: Twelve healthy subjects received 2 mg levosimendan i.v. both alone and in addition to a 7-9-day treatment with 25 mg carvedilol orally, twice daily, in a cross-over, placebo-controlled, double-blind, randomised study. Systolic time intervals, heart rate, and blood pressure were measured at baseline and up to 2 h after drug administration. Results: When levosimendan was administered in addition to carvedilol, the shortening of electromechanical systole QS2i (indicating increased contractility) was similar to that found with levosimendan alone (P=0.475). Also, the maximum heart rate change was similar, although a statistically significant difference in heart rate was detected due to minor differences at two time points during the 2-h follow-up (P=0.018). There were no differences in diastolic blood pressure response (P=0.962), but the systolic blood pressure response was attenuated by about 4 mmHg with the combination (P=0.013). Conclusions: The contractility enhancing effect of levosimendan was not altered in healthy subjects who had received carvedilol for at least 1 week. Heart rate and diastolic blood pressure responses were not altered either, while the systolic blood pressure response was blunted.