P Pollesello1, J Parissis2, M Kivikko3, V-P Harjola4. 1. Critical Care Proprietary Products, Orion Pharma, Espoo, Finland. Electronic address: piero.pollesello@orionpharma.com. 2. Second Department of Cardiology and Heart Failure Unit, University of Athens Medical School, Attikon University Hospital, Athens, Greece. 3. Critical Care Proprietary Products, Orion Pharma, Espoo, Finland. 4. Emergency Medicine, Helsinki University, Helsinki University Hospital, Helsinki, Finland.
Abstract
BACKGROUND: Levosimendan is an inodilator developed for treatment of acute heart failure and other cardiac conditions where the use of an inodilator is considered appropriate. Levosimendan has been studied in different therapeutic settings including acutely decompensated chronic heart failure, advanced heart failure, right ventricular failure, cardiogenic shock, septic shock, and cardiac and non-cardiac surgery. This variety of data has been re-analysed in 25 meta-analyses from 15 different international research groups, based on different rationales to select the studies included. METHODS: We here review all previously published meta-analyses on levosimendan to determine any common denominators for its effects on patient mortality. In addition, we also perform a comparative meta-analysis of the six phase II and III randomized double-blind trials which were taken into consideration by the regulatory authorities for the purpose of introducing levosimendan into the market. RESULTS: Irrespective of clinical setting or comparator, all meta-analyses consistently show benefits for levosimendan, with lower relative risk (or odds ratio) for patient mortality. In 3/25 of the meta-analyses these beneficial trends did not reach statistical significance, while in 22/25 significance was reached. The relative risk is consistent overall, and very similar to that obtained in our own meta-analysis that considered only the 'regulatory' studies. CONCLUSION: The existing meta-analyses, now based on a population of over 6000 patients, provide the general message of significant benefits for levosimendan in terms of patient mortality. The weight of evidence is now clearly in favour of usefulness/efficacy of levosimendan, with data from multiple randomized trials and meta-analyses.
BACKGROUND:Levosimendan is an inodilator developed for treatment of acute heart failure and other cardiac conditions where the use of an inodilator is considered appropriate. Levosimendan has been studied in different therapeutic settings including acutely decompensated chronic heart failure, advanced heart failure, right ventricular failure, cardiogenic shock, septic shock, and cardiac and non-cardiac surgery. This variety of data has been re-analysed in 25 meta-analyses from 15 different international research groups, based on different rationales to select the studies included. METHODS: We here review all previously published meta-analyses on levosimendan to determine any common denominators for its effects on patient mortality. In addition, we also perform a comparative meta-analysis of the six phase II and III randomized double-blind trials which were taken into consideration by the regulatory authorities for the purpose of introducing levosimendan into the market. RESULTS: Irrespective of clinical setting or comparator, all meta-analyses consistently show benefits for levosimendan, with lower relative risk (or odds ratio) for patient mortality. In 3/25 of the meta-analyses these beneficial trends did not reach statistical significance, while in 22/25 significance was reached. The relative risk is consistent overall, and very similar to that obtained in our own meta-analysis that considered only the 'regulatory' studies. CONCLUSION: The existing meta-analyses, now based on a population of over 6000 patients, provide the general message of significant benefits for levosimendan in terms of patient mortality. The weight of evidence is now clearly in favour of usefulness/efficacy of levosimendan, with data from multiple randomized trials and meta-analyses.
Authors: Christoph Maack; Thomas Eschenhagen; Nazha Hamdani; Frank R Heinzel; Alexander R Lyon; Dietmar J Manstein; Joseph Metzger; Zoltán Papp; Carlo G Tocchetti; M Birhan Yilmaz; Stefan D Anker; Jean-Luc Balligand; Johann Bauersachs; Dirk Brutsaert; Lucie Carrier; Stefan Chlopicki; John G Cleland; Rudolf A de Boer; Alexander Dietl; Rodolphe Fischmeister; Veli-Pekka Harjola; Stephane Heymans; Denise Hilfiker-Kleiner; Johannes Holzmeister; Gilles de Keulenaer; Giuseppe Limongelli; Wolfgang A Linke; Lars H Lund; Josep Masip; Marco Metra; Christian Mueller; Burkert Pieske; Piotr Ponikowski; Arsen Ristić; Frank Ruschitzka; Petar M Seferović; Hadi Skouri; Wolfram H Zimmermann; Alexandre Mebazaa Journal: Eur Heart J Date: 2019-11-21 Impact factor: 29.983
Authors: Johann Altenberger; Finn Gustafsson; Veli-Pekka Harjola; Kristjan Karason; Detlef Kindgen-Milles; Matti Kivikko; Gabriella Malfatto; Zoltán Papp; John Parissis; Piero Pollesello; Gerhard Pölzl; Carsten Tschöpe Journal: J Cardiovasc Pharmacol Date: 2018-03 Impact factor: 3.105
Authors: Mohammed Elzeneini; Juan M Aranda; Mohammad Al-Ani; Mustafa M Ahmed; Alex M Parker; Juan R Vilaro Journal: Heart Fail Rev Date: 2020-09-30 Impact factor: 4.214