Dose-ranging and safety with intravenous levosimendan in low-output heart failure: Experience in three pilot studies and outline of the levosimendan infusion versus dobutamine (LIDO) trial

A series of dose-ranging and tolerability studies of intravenous levosimend an (bolus then infusion) were conducted in 40 patients with low-output hear t failure (cardiac index <2.5 L/m(2) per minute). These trials were conduct ed as preparation for the Levosimendan Infusion versus Dobutamine (LIDO) st udy, an international, randomized, comparative phase III trial of intraveno us levosimendan versus dobutamine in heart failure. Response rates to levos imendan therapy (defined as greater than or equal to 30% Increase In cardia c index during levosimendan administration) were 73-100% (compared with 60% with dobutamine 8-16 mu g/kg per minute). Dose dependence was apparent in several hemodynamic responses to levosimendan. From experience in these stu dies it was concluded that the preferred bolus dose for initiating levosime ndan therapy was 12-24 mu g/kg, followed by infusion at rates vp to 0.4 mu g/kg per minute. It was also concluded that, in the dose range identified, levosimendan offered a valid alternative to dobutamine in heart failure pat ients who require intravenous inotropic support. (C) 1999 by Excerpta Medic a, Inc.