EXPERT OPINION ON PHARMACOTHERAPY, vol.8, no.5, pp.665-677, 2007 (SCI-Expanded)
Levosimendan is a new calcium sensitizer with inotropic and vasodilatory actions mediated by the sensitization of contractile proteins to calcium, opening of potassium channels and inhibition of phosphodiesterase-3. Its alternative mechanisms of action to those of other traditional inotropes provide a new approach in the management of decompensated heart failure. in contrast to dobutamine, levosimendan does not increase myocardial oxygen demand and, therefore, it is thought to have a lower potential to induce increases in myocardial ischemia and cardiac arrhythmias. The commonly used inotropic agent dobutamine increases myocardial contractility at the expense of increased myocardial oxygen consumption and, therefore, it can result in poor outcomes. Although dobutamine may also have favorable hemodynamic and symptomatic effects, levosimenclan has been shown to be superior to dobutamine in increasing cardiac output and decreasing pulmonary capillary wedge pressure in patients with decompensated heart failure. In the presence of concomitant p-blocker therapy, these favorable effects were present or even more pronounced during treatment with levosimenclan, but not clobutamine. However, the mortality benefit of levosimendan observed in earlier trials has not been confirmed in recent, larger clinical trials. A distinct advantage of levosimenclan over dobutamine is its prolonged hemodynamic effects, which last for up to 7 - 9 days. There are more data on the safety of levosimendan in ischemic patients than with any other inotropic drug and, therefore, levosimenclan seems to be safe and effective in patients with ischemic heart disease when used at the recommended doses. Despite advances in heart failure therapy, many patients experience clinical deterioration, or do not respond to a single inotropic drug. Increasing evidence suggests the use of levosimendan in combination with dobutamine in patients with decompensated heart failure that is refractory to dobutamine alone.