Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:243

Article

Poelzl, Gerhard¹  Altenberger, Johann²  Baholli, Loant³  Beltran, Paola⁴  Borbely, Attila⁵  Comin-Colet, Josep⁶  Delgado, Juan F.⁷  Fedele, Francesco⁸  Fontana, Antonella⁹  Fruhwald, Friedrich¹⁰  Giamouzis, Gregory¹¹  Giannakoulas, George¹²  Garcia-Gonzalez, Martin J.¹³  Gustafsson, Finn¹⁴  Kaikkonen, Kari¹⁵  Kivikko, Matti¹⁶  Kubica, Jacek¹⁷  von Lewinski, Dirk¹⁰  Lofman, Ida¹⁸  Malfatto, Gabriella¹⁹  Manito, Nicolas⁶  Martinez-Selles, Martin²⁰  Masip, Josep⁴  Merkely, Bela²¹  Morandi, Fabrizio²²  Molgaard, Henning²³  Oliva, Fabrizio²⁴  Pantev, Emil²⁵  Papp, Zoltan⁵  Perna, Gian Piero²⁶  Pfister, Roman²⁷  Piazza, Vito²⁸  Bover, Ramon²⁹  Rangel-Sousa, Diego³⁰  Recio-Mayoral, Alejandro³¹  Reinecke, Alexander³²  Rieth, Andreas³³  Sarapohja, Toni¹⁶  Schmidt, Gunter³⁴  Seidel, Mirko³⁵  Stoerk, Stefan^36,37  Vrtovec, Bojan³⁸  Wikstroem, Gerhard³⁹  Yerly, Patrik⁴⁰  Pollesello, Piero¹⁶ 

[1] Univ Klin Innsbruck, Innsbruck, Austria

[2] Rehabil Zentrum Grossgmain, Salzburg, Austria

[3] Klinikum Dortmund Mitte, Dortmund, Germany

[4] HM Broggi, Barcelona, Spain

[5] Univ Debrecen, Fac Med, Div Clin Physiol, Debrecen, Hungary

[6] Univ Hosp Bellvitge, Barcelona, Spain

[7] Hosp 12 Octubre, Madrid, Spain

[8] Sapienza Univ, Policlin Umberto 1, Rome, Italy

[9] Orion Pharma Srl, Milan, Italy

[10] Med Univ Klin, Graz, Austria

[11] Univ Thessaly, Larissa Univ Hosp, Larisa, Greece

[12] Aristotle Univ Thessaloniki, Thessaloniki, Greece

[13] H La Laguna, Tenerife, Spain

[14] Rigshosp, Copenhagen, Denmark

[15] Oulu Univ Hosp, Oulu, Finland

[16] Orion Pharma, Espoo, Finland

[17] Nicolaus Copernicus Univ, Coll Med, Bydgoszcz, Poland

[18] Karolinska Univ Sjukhus Huddinge, Huddinge, Sweden

[19] Ist Auxol Italiano, Milan, Italy

[20] H Gregorio Maranon, Madrid, Spain

[21] Semmelweis Univ, Heart & Vasc Ctr, Budapest, Hungary

[22] Circolo Hosp & Macchi Fdn, Varese, Italy

[23] Aarhus Univ Hosp, Skejby, Denmark

[24] Osped Niguarda Ca Granda, Milan, Italy

[25] Helsingborgs Iasarett, Helsingborg, Sweden

[26] Osped Riuniti, Dipartimento Sci Cardiol Med Chirurg, Ancona, Italy

[27] Univ Cologne, Herzzentrum, Klin Innere Med 3, Cologne, Germany

[28] Azienda Osped San Camillo Forlanini, Rome, Italy

[29] H Clin San Carlos, Madrid, Spain

[30] H Virgen Rocio, Seville, Spain

[31] Hosp Univ Virgen Macarena, Seville, Spain

[32] Uni Klinikum Schleswig Holstein, Kiel, Germany

[33] Kerckhoff Klin, Bad Nauheim, Germany

[34] CHARITE Univ Med Berlin, Berlin, Germany

[35] Unfallkrankenhaus Berlin, Innere Med Klin, Berlin, Germany

[36] Univ Wurzburg, Comprehens Heart Failure Ctr, Wurzburg, Germany

[37] Univ Hosp, Wurzburg, Germany

[38] Univ Clin Ctr, Ljubljana, Slovenia

[39] Uppsala Univ, Inst Med Sci, Uppsala, Sweden

[40] CHU Vaudois, Lausanne, Switzerland

关键词: Advanced heart failure;    Levosimendan;    Intermittent;    Repetitive;    Clinical trial;    Composite end-point;   

DOI  :  10.1016/j.ijcard.2017.05.081

来源: Elsevier

【 摘 要 】

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminalprohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.

【 授权许可】

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