Evidence and Current Use of Levosimendan in the Treatment of Heart Failure: Filling the Gap

Abstract

Levosimendan is a distinctive inodilator combing calcium sensitization, phosphodiesterase inhibition and vasodilating properties through the opening of adenosine triphosphate-dependent potassium channels. It was first approved in Sweden in 2000 for the short-term treatment of acutely decompensated severe chronic heart failure when conventional therapy is not sufficient, and in cases where inotropic support is considered appropriate. After more than 20 years, clinical applications have considerably expanded across critical care and emergency medicine, and levosimendan is now under investigation in different cardiac settings (eg, septic shock, pulmonary hypertension) and for non-cardiac applications (eg, amyotrophic lateral sclerosis). This narrative review outlines key milestones in levosimendan history, by addressing regulatory issues, pharmacological peculiarities and clinical aspects (efficacy and safety) of a drug that did not receive great attention in the heart failure guidelines. A brief outlook to the ongoing clinical trials is also offered.

Levosimendan Administration May Provide More Benefit for Survival in Patients with Non-Ischemic Cardiomyopathy Experiencing Acute Decompensated Heart Failure

“…In the patients with decompensated status requiring inotropes or intravenous diuretics, levosimendan may improve diastolic and systolic functions of both ventricles, but the benefits of hard endpoints, including hospitalizations and mortality, are contradictory [ 25 , 26 ]. In a randomized study on CV surgery, there was the trend of better outcomes upon use of levosimendan as compared to placebo use; however, significantly better outcomes were observed only in the subgroup of patients who underwent isolated coronary artery bypass graft surgery [ 27 ].…”

“…Levosimendan had a long half-life, and its delayed action necessitates a high loading dose [ 26 ]. Moreover, its use in patients with CS is associated with potential adverse effects such as hypotension [ 26 ].…”

“…Levosimendan had a long half-life, and its delayed action necessitates a high loading dose [ 26 ]. Moreover, its use in patients with CS is associated with potential adverse effects such as hypotension [ 26 ]. A large retrospective analysis of three observational cohorts of patients with ADHF suggested that combining a vasopressor with an inodilator may improve short-term mortality in patients with CS compared with use of vasopressors alone [ 27 ].…”

“…In the patients with decompensated status requiring inotropes or intravenous diuretics, levosimendan may improve diastolic and systolic functions of both ventricles, but the benefits of hard endpoints, including hospitalizations and mortality, are contradictory [25,26].…”

Intraoperative Circulatory Support in Lung Transplantation: Current Trend and Its Evidence

“…There is a lack of robust data to definitively recommend specific catecholamine therapies. However, levosimendan seems to be a useful and promising option in selected cases [ 88 , 89 ]. To reduce RV afterload, the inhalation of NO or iloprost has equal effects [ 75 ].…”