, Volume 49, Issue 6, pp 451-458

Haemodynamic interactions of a new calcium sensitizing drug levosimendan and captopril

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Abstract

Objective: Levosimendan in a new inodilator drug that sensitises troponin C in heart muscle cells to calcium, thus improving contractility. In previous studies, a single 2 mg intravenous dose of levosimendan increased cardiac output (CO) in healthy volunteers by about 40% and decreased pulmonary capillary wedge pressure in heart failure patients by 40–50%.

The aim of the present, double-blind study was to evaluate the safety of concomitant use of levosimendan and an ACE-inhibiting drug.

Methods: The haemodynamic effects of levosimendan, given with or without captopril, were evaluated by using 2-dimensional echocardiography, repeated blood pressure measurements and by ambulatory ECG recordings. Twenty-four male patients with stable NYHA II-III heart failure (EF<40%) after a previous myocardial infarct were given, in randomised order, a single IV infusion of levosimendan or placebo. The infusions were repeated after 2 weeks treatment with upto 50 mg b.i.d. of captopril. Twelve patients received levosimendan 1 mg and twelve received 2 mg.

Results: Mean CO was increased from 6.0 to 6.81·min−1 in patients receiving 1 mg levosimendan compared to placebo, but only from 6.3 to 6.51·min−1 in patients receiving 2 mg. The increase in CO was statistically significant when all levosimendan patients were compared to placebo. Heart rate did not change after either dose. Mean stroke volume increased significantly after 1 mg but not after 2 mg of levosimendan. The addition of captopril did not change the effects of levosimendan. No additional decrease in systolic or diastolic blood pressure was observed when levosimendan and captopril were given concomitantly.

Conclusion: It seems that concomitant treatment with captopril does not change the haemodynamic effects of levosimendan. No adverse haemodynamic interactions were seen.