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Review
. 2020 Jul 8:6:e19.
doi: 10.15420/cfr.2020.03. eCollection 2020 Mar.

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

Zoltán Papp  1 , Piergiuseppe Agostoni  2 , Julian Alvarez  3 , Dominique Bettex  4 , Stefan Bouchez  5 , Dulce Brito  6 , Vladimir Černý  7 , Josep Comin-Colet  8 , Marisa G Crespo-Leiro  9 , Juan F Delgado  10 , Istvan Édes  1 , Alexander A Eremenko  11 , Dimitrios Farmakis  12 , Francesco Fedele  13 , Cândida Fonseca  14 , Sonja Fruhwald  15 , Massimo Girardis  16 , Fabio Guarracino  17 , Veli-Pekka Harjola  18 , Matthias Heringlake  19 , Antoine Herpain  20 , Leo Ma Heunks  21 , Tryggve Husebye  22 , Višnja Ivancan  23 , Kristjan Karason  24 , Sundeep Kaul  25 , Matti Kivikko  26 , Janek Kubica  27 , Josep Masip  28 , Simon Matskeplishvili  29 , Alexandre Mebazaa  30 , Markku S Nieminen  31 , Fabrizio Oliva  32 , Julius-Gyula Papp  33 , John Parissis  34 , Alexander Parkhomenko  35 , Pentti Põder  36 , Gerhard Pölzl  37 , Alexander Reinecke  38 , Sven-Erik Ricksten  39 , Hynek Riha  40 , Alain Rudiger  41 , Toni Sarapohja  42 , Robert Hg Schwinger  43 , Wolfgang Toller  44 , Luigi Tritapepe  45 , Carsten Tschöpe  46 , Gerhard Wikström  47 , Dirk von Lewinski  48 , Bojan Vrtovec  49 , Piero Pollesello  50
Affiliations
Review

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

Zoltán Papp et al. Card Fail Rev. .

Abstract

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.

Keywords: Acute heart failure; advanced heart failure; haemodynamics; inodilator; inotrope; neurohormone; regulatory clinical trial.

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Conflict of interest statement

Disclosure: PP, TS and MK are full- or part-time employees of Orion Pharma. In the past 5 years, all other authors have received honoraria from Orion Pharma for educational lectures and/or unrestricted grants for investigator-initiated studies.

Figures

Figure 1:
Figure 1:. Early Molecular Model of the Levosimendan–cTnC Complex
Figure 2:
Figure 2:. Mode of Actions and Pharmacological Effects of Levosimendan
Figure 3:
Figure 3:. Change in Cardiac Output and Pulmonary Capillary Wedge Pressure
Figure 4:
Figure 4:. Pharmacokinetics of Levosimendan
Figure 5:
Figure 5:. Effect of Levosimendan on Survival in the Regulatory Clinical Trials
Figure 6:
Figure 6:. Results of 64 Meta-analyses of Levosimendan Clinical Trials
See this image and copyright information in PMC

References

    1. Beregovich J, Bianchi C, D’Angelo R et al. Haemodynamic effects of a new inotropic agent (dobutamine) in chronic cardiac failure. Br Heart J. 1975;37:629–34. doi: 10.1136/hrt.37.6.629. - DOI - PMC - PubMed
    1. Fabiato A, Fabiato F. Calcium and cardiac excitation-contraction coupling. Ann Rev Physiol. 1979;41:473–84. doi: 10.1146/annurev.ph.41.030179.002353. - DOI - PubMed
    1. Wohlfart B, Noble MI. The cardiac excitation-contraction cycle. Pharmacol Ther. 1982;16:1–43. doi: 10.1016/0163-7258(82)90030-4. - DOI - PubMed
    1. Colucci WS, Wright RF, Braunwald E. New positive inotropic agents in the treatment of congestive heart failure. Mechanisms of action and recent clinical developments. 1. N Engl J Med. 1986;314:290–9. doi: 10.1056/NEJM198602063140605. - DOI - PubMed
    1. Maskin CS, Sinoway L, Chadwick B et al. Sustained hemodynamic and clinical effects of a new cardiotonic agent, WIN 47203, in patients with severe congestive heart failure. Circulation. 1983;67:1065–70. doi: 10.1161/01.cir.67.5.1065. - DOI - PubMed