Levosimendan boosts function in severe CHF: mortality at 31 days was 7.8% with levosimendan and 17% with dobutamine. (Investigational Drug).
In a series of studies presented at the meeting, the cardiac improvements seen during and after 24-hour intravenous infusions of the investigational calcium sensitizer were shown to be comparable to those achieved after a 48-hour infusion, Dr. Colucci said. The findings indicate 24-hour infusion is the optimal treatment.
The placebo-controlled clinical trial randomized 146 patients hospitalized with severe congestive heart failure to either a 6-hour infusion of placebo or a 6-hour infusion of levosimendan in escalating doses, with the maximum dose being 0.4 [micro]g/kg per minute.
In a second phase of the study, the levosimendan group continued to receive levosimendan for another 18 hours at half the initial dose, for a total treatment time of 24 hours. In a third phase, the levosimendan patients were randomized to placebo or a continuing infusion of levosimendan for another 24 hours, at the dose used in the previous study.
At 6 hours, the levosimendan group exhibited cardiac pefformance improvement in every category measured, compared with the placebo group.
Stroke volume in the levosimendan group increased an average of 13% but decreased an average of 1.4% in the placebo group. Pulmonary artery capillary wedge pressure decreased an average of 6.4 % in the levosimendan group but increased an average of 0.1% in the placebo group. Significantly more levosimendan than placebo patients reported improvement in dyspnea at 6 hours; however after 6 hours there was no significant difference in dyspnea improvement.
Over the next 18 hours, pulmonary capillary wedge pressure and systemic vascular resistance continued to decrease in the levosimendan group. Stroke volume and cardiac output increased after 24 hours, but not significantly.
The improvements in the levosirnendan group were sustained at 48 hours regardless of whether the patients received placebo or continued levosimendan treatment in the third part of the studies.
The continued cardiac performance improvement after withdrawal of levosimendan beyond 24 hours and the comparable results of cardiac improvements at 24 and 48 hours indicate that a 24-hour infusion is the best treatment, Dr. Colucci concluded.
He said that the long-lasting plasma concentration of OR-1896, a metabolire of levosimendan, is likely associated with these prolonged improvements.
Levosimendan is used in some European countries for the treatment of severe heart failure, but has not been approved for use in the United States.
A recently published European study of 203 heart failure patients treated with levosimendan or dobutamine conduded that levosimendan cut the 31-day mortality of these patients by about 50%, from 17% in the dobutamine group to 7.8% in the levosimendan group (Lancet 360:196202, 2002).
At 6 months, the mortality of the 1evosimendan patients remained lower at 26%, compared with the 38% mortality of the dobutamine patients.
The drug acts by increasing myocardial contractile force and inducing vasodilation by sensitizing the cardiac myocytes to calcium and opening the ATP-sensitive potassium channels.
These actions do not result in a significant increase in myocardial oxygen consumption, Dr. Colucci said.
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|Title Annotation:||congestive heart failure|
|Author:||Sullivan, Michele G.|
|Publication:||Internal Medicine News|
|Date:||Sep 15, 2002|
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