Levosimendan: a review of its use in the management of acute decompensated heart failure.
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.


CONCLUSIONS
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.
Innes
Carmen A
CA
Adis International Limited, Auckland, New Zealand.
Wagstaff
Antona J
AJ
D000208:Acute Disease; D000818:Animals; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011724:Pyridazines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000077464:Simendan
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan