Sustained Hemodynamic Effects of Intravenous Levosimendan

Abstract

Background-The short-term infusion of levosimendan (Levo) improves hemodynamic function in patients with decompensated heart failure. The metabolites of Levo have a prolonged half-life, and one is hemodynamically active. The goal of this study was to determine whether the hemodynamic effects of Levo are sustained during a long-term infusion and beyond the discontinuation of drug infusion. Methods and Results-Patients with decompensated heart failure received escalating infusion rates of intravenous Levo (nϭ98) or placebo (nϭ48) for 6 hours. At the end of 6 hours, 85 of the Levo-treated patients were continued on open-label drug for a total of 24 hours, at which time they were randomized 1:1 to an additional 24 hours of Levo (nϭ43) or placebo (nϭ42).The hemodynamic effects observed at 24 hours were maintained at 48 hours in both the continuation and withdrawal groups and did not differ between groups. Although the plasma concentration of Levo decreased rapidly in the withdrawal group, concentrations of the active metabolite OR-1896 were similar in the continuation and withdrawal groups at 24 hours and increased further (3.5-fold to 4-fold) and to a similar extent in both groups at 48 hours. Conclusions-The hemodynamic effects of Levo were maintained during a 48-hour continuous infusion and for at least 24 hours after discontinuation of a 24-hour infusion. The active metabolite OR-1896 increased for at least 24 hours after cessation of drug infusion and may account for the prolonged hemodynamic effects of Levo.

Levosimendan restores the positive force-frequency relation in heart failure

“…The plasma levels of levosimendan were similar to previous human (9,30,48) and animal experimental investigations (3,37,46,52).…”

European Experience on the Practical Use of Levosimendan in Patients with Acute Heart Failure Syndromes

“…In 6 patients, planned readministration maintained clinical improvement, whereas in 3 patients rehospitalized for further acute clinical deterioration, repeated treatment with levosimendan could not prevent a fatal outcome. In view of the long-lasting hemodynamic improvement because of a long-acting metabolite (half-life, approximately 80 hours), 16 levosimendan appears to be a suitable drug for repetitive treatment of patients with advanced HF as a bridge to cardiac transplantation. Large-scale trials including comparison with other drugs used for similar indications should be conducted.…”

The effect of levosimendan and dobutamine treatment on QT dispersion in patients with decompensated heart failure: a prospective study

“…Levosimendanın aritmojenik etkilerini değerlendiren plasebo kontrollü çalışmalar bulunmasına karşın, levosimendan ile dobutamin aritmojeniteleri açısından karşılaştıran veriler genellikle levosimendanın mortalite ve klinik etkinliğine ilişkin yapılan çalışmalar sırasında gözlenen aritmilerin analizlerine dayanmaktadır (25)(26)(27)(28)(29)(30)(31). LIDO ve SURVIVE çalışmasında aritmi değer-lendirmeleri için Holter kaydı kullanılmamış, Tek ve ark.nın (25) yaptıkları çalışmada ise bu aritmileri değerlendirmek için Holter kaydı kullanılmış.…”

“…Levosimendan ile yapılan birçok klinik çalışmada, supraventriküler taşikardi, ventriküler taşikardi ve proaritmi riski açısından levosimendanın standart tedaviden farksız olduğu gözlenmiştir (26)(27)(28)(29)(30)(31). Fakat daha sonra yapılan REVIVE II çalışmasında; akut dekompanse kalp yetersizlikli 600 hasta çalışmaya alınmış, standart tedaviye ek olarak levosimendan alan grup, standart tedaviyle birlikte plasebo alan grupla klinik bulgular ve semptomlar açısından karşılaştırılmıştır.…”