Considerations on the efficacy and safety of levosimendan in ischemic heart failure.
Levosimendan is a new vasodilator agent with properties which improve cardiac contractility by calcium sensitization. Its dose-related efficacy and prolonged action have been documented in several major studies both against placebo and dobutamine. Out of 997 patients, 837 (84%) had acute or stable heart failure due to coronary heart disease. Therefore, it would be most interesting to analyze the efficacy and safety of levosimendan in heart failure due to ischemic heart disease. The dose-finding study included 98 patients who were given intravenous levosimendan at different doses and 20 patients treated with dobutamine. All patients had heart failure due to coronary heart disease. The other major trial included 500 acute myocardial infarction patients with heart failure and was placebo-controlled. In other levosimendan vs placebo or dobutamine comparative trials 50-60% of patients had ischemic heart disease and severe heart failure. Levosimendan significantly improves the cardiac index by 30-39% at bolus doses of 6-24 micrograms/kg/min followed by infusion doses of 0.05-0.2 microgram/kg/min and reduces the wedge pressure by 20-25% to optimal levels (from 15-20 mmHg). There is a lesser blood pressure reduction and some heart rate increase. However in patients with an acute myocardial infarction the rate of ischemia or hypotension were similar in levosimendan- and placebo-treated patients and in the dobutamine controlled trials no major adverse effects were seen or they were more frequent in dobutamine patients. There is no increase in mortality either compared to placebo or to dobutamine. Rather, the opposite seems to be true. No increase in arrhythmias is seen. The hemodynamic effects of levosimendan are dose-dependent and the current recommended doses are safe. No increase in mortality or any life-threatening arrhythmias have been observed.
Nieminen
Markku S
MS
Division of Cardiology, University Central Hospital, 00290 Helsinki, Finland. markku.nieminen@hus.fi
Sandell
Esa-Pekka
EP
D020746:Calcium Channels, L-Type / Q000627:therapeutic use*; D005062:European Union; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D009017:Morbidity; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D011724:Pyridazines / Q000627:therapeutic use*; D000077464:Simendan; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014665:Vasodilator Agents / Q000627:therapeutic use*
D020746:Calcium Channels, L-Type; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan