Levosimendan: a new era for inodilator therapy for heart failure?
Levosimendan is a new inotropic and vasodilator agent. The inotropic effect is mediated by calcium concentration-dependent conformational changes in troponin C during systole leading to sensitization of the contractile apparatus to calcium ions. The vasodilator effect is mediated by opening potassium channels on vascular smooth muscle. It has a complex pharmacokinetic profile, with a long-acting metabolite that has hemodynamic effects persisting for approximately 1 week. Although it is absorbed orally, it has been developed only for intravenous use thus far. The hemodynamic effects are not reduced and may be enhanced in the presence of beta-blockers, possibly an important attribute when dealing with exacerbation of heart failure caused by or in the presence of beta-blockers. More patients with heart failure have participated in randomized controlled trials of levosimendan than of any other intravenous inotropic agent. Experience with its use after cardiac surgery is limited. Preliminary observations suggest that hemodynamic changes are associated with symptomatic benefit and a reduction in morbidity and mortality in patients with severe heart failure caused by left ventricular systolic dysfunction, compared with placebo in one study and dobutamine in another. Levosimendan may be the first inotropic agent that it is both safe and effective in altering clinical outcomes relevant for patients. Part of this benefit may be achieved because levosimendan allows other inotropic agents that may have adverse effects on patient outcome to be avoided. Further research is required to confirm whether levosimendan reduces mortality and morbidity compared with a placebo and when administered repetitively. If it does, it may become routine therapy for the treatment of severe heart failure.
Cleland
John G F
JG
Department of Cardiology, Castle Hill Hospital, University of Hull, Cottingham, Kingston upon Hull, United Kingdom. G.M.Porter@hull.ac.uk
McGowan
James
J
D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D011724:Pyridazines / Q000627:therapeutic use*; D000077464:Simendan; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan