Levosimendan: first in a new class of inodilator for acute and chronic severe heart failure.
Heart failure is the most common malignant disease in the developed world. Levosimendan (Simdax) is a novel intravenous agent that exerts inotropic effects through sensitization of myofilaments to calcium and vasodilator effects by opening ATP-dependent potassium channels on vascular smooth muscle. Infusion of levosimendan increases cardiac output due to an increase in stroke volume and heart rate, with a fall in pulmonary capillary wedge pressure. It has an active metabolite with a half-life of about 80 h, therefore infusions of 6 to 24 h result in hemodynamic effects that persist for 7 to 10 days. Preliminary observations suggest that a single infusion of levosimendan lasting 6 to 24 h in patients with severe heart failure due to left ventricular systolic dysfunction results in hemodynamic changes, symptomatic benefit and a reduction in morbidity and mortality over the following 2 to 4 weeks compared with placebo in one study and with dobutamine in another. Long-term follow-up suggests no loss of this early benefit over 6 months. Levosimendan is licensed for the treatment of decompensated heart failure in many countries but not in North America. Further large trials are being conducted comparing levosimendan with placebo and with dobutamine in patients with severe heart failure and left ventricular systolic dysfunction. If these studies confirm the benefits of levosimendan, then it may become routine therapy for the management of severe heart failure.
Cleland
John G F
JG
Department of Cardiology, Castle Hill Hospital, Cottingham, Kington upon Hull, UK. J.G.Cleland@hull.ac.uk
Nikitin
Nikolay
N
McGowan
James
J
D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011724:Pyridazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012449:Safety; D000077464:Simendan; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan