Levosimendan (Simdax) is a
calcium-sensitising
drug that stabilises the
troponin molecule in cardiac muscle, thus prolonging its effects on
contractile proteins, with concomitant vasodilating properties. Intravenous
levosimendan (12-24 microg/kg loading dose followed by 0.1-0.2 microg/kg/min for 24 hours, adjusted for response and tolerability) is approved for the short-term treatment of acute severe decompensated
heart failure. Cardiac output increased by about 30% and pulmonary capillary wedge pressure and systemic vascular resistance decreased by about 17-29% in patients with decompensated
heart failure receiving intravenous
levosimendan. In large, well controlled trials in patients with decompensated
heart failure, intravenous
levosimendan was significantly more effective than placebo or
dobutamine for overall haemodynamic response rate (primary endpoint). Significant benefits were also seen for mortality (versus placebo or
dobutamine) and for the combined risk of worsening
heart failure or death (versus
dobutamine). Improvements in key symptoms (dyspnoea and
fatigue) have not been consistently demonstrated. Hospitalisation costs were similar for
levosimendan and
dobutamine; the total incremental (hospitalisation plus drug) cost per life-year saved (extrapolated to 3 years) for
levosimendan relative to
dobutamine was estimated at Euro 3205 (year of costing 2000).
Levosimendan is generally well tolerated, with an adverse event profile at recommended dosages similar to that in patients receiving placebo. Cardiac rate/rhythm disorders and
headache were the most common events. At higher dosages, patients receiving
levosimendan had higher rates of
sinus tachycardia than those in placebo recipients. More patients receiving
dobutamine than those receiving
levosimendan experienced
angina pectoris/
chest pain/myocardial ischaemia or rate/rhythm disorders.
CONCLUSION: Intravenous
levosimendan is an effective
calcium-sensitising
drug with vasodilatory and inotropic effects, and superior efficacy/tolerability to those of intravenous
dobutamine in patients with acute decompensated
heart failure. It may be associated with reduced mortality compared with both placebo and
dobutamine.
Levosimendan is generally well tolerated and may have less potential for cardiac rate/rhythm disorders than
dobutamine. While evidence from well designed trials confirming the improved mortality over
dobutamine and investigating haemodynamic efficacy and mortality versus other positive inotropes is required, intravenous
levosimendan appears to be a useful addition to the treatment options for acute decompensated
heart failure in patients with
low cardiac output.