Sean van Diepen1, Rajendra H Mehta2, Jeffrey D Leimberger2, Shaun G Goodman3, Stephen Fremes4, Rachael Jankowich5, Matthias Heringlake6, Kevin J Anstrom2, Jerrold H Levy2, John Luber7, A Dave Nagpal8, Andra E Duncan9, Michael Argenziano10, Wolfgang Toller11, Kevin Teoh12, J David Knight2, Renato D Lopes2, Patricia A Cowper2, Daniel B Mark2, John H Alexander2. 1. Division of Cardiology, Departments of Critical Care and Medicine, University of Alberta, Edmonton, Alberta, Canada; Canadian VIGOUR Center, University of Alberta, Edmonton, Alberta, Canada. Electronic address: sv9@ualberta.ca. 2. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC. 3. Canadian VIGOUR Center, University of Alberta, Edmonton, Alberta, Canada; Terrence Donnelly Heart Centre, Division of Cardiology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 4. Schulich Heart Center, University of Toronto, Toronto, Ontario, Canada. 5. Tenax Therapeutics, Morrisville, NC. 6. University of Lübeck, Lübeck, Germany. 7. Franciscan Health System, Tacoma, Wash. 8. London Health Sciences Centre, London, Ontario, Canada. 9. Cleveland Clinic, Cleveland, Ohio. 10. Columbia University Medical Center, New York, NY. 11. Medical University of Graz, Graz, Austria. 12. Southlake Regional Health Center, Newmarket, Ontario, Canada.
Abstract
OBJECTIVE: In the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial, no differences in clinical outcomes were observed between levosimendan and placebo in a broad population of patients undergoing cardiac surgery. In previous studies, the benefits of levosimendan were most clearly evident in patients undergoing isolated coronary artery bypass grafting (CABG) surgery. In a prespecified analysis of LEVO-CTS, we compared treatment-related outcomes and costs across types of cardiac surgical procedures. METHODS: Overall, 563 (66.4%) patients underwent isolated CABG, 97 (11.4%) isolated valve, and 188 (22.2%) combined CABG/valve surgery. Outcomes included the co-primary 4-component composite (30-day mortality, 30-day renal replacement, 5-day myocardial infarction, or 5-day mechanical circulatory support), the 2-component composite (30-day mortality or 5-day mechanical circulatory support), 90-day mortality, low cardiac output syndrome (LCOS), and 30-day medical costs. RESULTS: The 4- and 2-component outcomes were not significantly different with levosimendan and placebo in patients undergoing CABG (15.2% vs 19.3% and 7.8% vs 10.4%), valve (49.0% vs 33.3% and 22.4% vs 2.1%), or combined procedures (39.6% vs 35.9% and 24.0% vs 19.6%). Ninety-day mortality was lower with levosimendan in isolated CABG (2.1% vs 7.9%; hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.11-0.64), but not significantly different in valve (8.3% vs 2.0%; HR, 4.10; 95% CI, 0.46-36.72) or combined procedures (10.4% vs 7.6%; HR, 1.39; 95% CI, 0.53-3.64; interaction P = .011). LCOS (12.0% vs 22.1%; odds ratio, 0.48; 95% CI, 0.30-0.76; interaction P = .118) was significantly lower in levosimendan-treated patients undergoing isolated CABG. Excluding study drug costs, median and mean 30-day costs were $53,707 and $65,852 for levosimendan and $54,636 and $67,122 for placebo, with a 30-day mean difference (levosimendan - placebo) of -$1270 (bootstrap 95% CI, -$8722 to $6165). CONCLUSIONS:Levosimendan was associated with lower 90-day mortality and LCOS in patients undergoing isolated CABG, but not in those undergoing isolated valve or combined CABG/valve procedures.
RCT Entities:
OBJECTIVE: In the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial, no differences in clinical outcomes were observed between levosimendan and placebo in a broad population of patients undergoing cardiac surgery. In previous studies, the benefits of levosimendan were most clearly evident in patients undergoing isolated coronary artery bypass grafting (CABG) surgery. In a prespecified analysis of LEVO-CTS, we compared treatment-related outcomes and costs across types of cardiac surgical procedures. METHODS: Overall, 563 (66.4%) patients underwent isolated CABG, 97 (11.4%) isolated valve, and 188 (22.2%) combined CABG/valve surgery. Outcomes included the co-primary 4-component composite (30-day mortality, 30-day renal replacement, 5-day myocardial infarction, or 5-day mechanical circulatory support), the 2-component composite (30-day mortality or 5-day mechanical circulatory support), 90-day mortality, low cardiac output syndrome (LCOS), and 30-day medical costs. RESULTS: The 4- and 2-component outcomes were not significantly different with levosimendan and placebo in patients undergoing CABG (15.2% vs 19.3% and 7.8% vs 10.4%), valve (49.0% vs 33.3% and 22.4% vs 2.1%), or combined procedures (39.6% vs 35.9% and 24.0% vs 19.6%). Ninety-day mortality was lower with levosimendan in isolated CABG (2.1% vs 7.9%; hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.11-0.64), but not significantly different in valve (8.3% vs 2.0%; HR, 4.10; 95% CI, 0.46-36.72) or combined procedures (10.4% vs 7.6%; HR, 1.39; 95% CI, 0.53-3.64; interaction P = .011). LCOS (12.0% vs 22.1%; odds ratio, 0.48; 95% CI, 0.30-0.76; interaction P = .118) was significantly lower in levosimendan-treated patients undergoing isolated CABG. Excluding study drug costs, median and mean 30-day costs were $53,707 and $65,852 for levosimendan and $54,636 and $67,122 for placebo, with a 30-day mean difference (levosimendan - placebo) of -$1270 (bootstrap 95% CI, -$8722 to $6165). CONCLUSIONS:Levosimendan was associated with lower 90-day mortality and LCOS in patients undergoing isolated CABG, but not in those undergoing isolated valve or combined CABG/valve procedures.
Authors: Zoltán Papp; Piergiuseppe Agostoni; Julian Alvarez; Dominique Bettex; Stefan Bouchez; Dulce Brito; Vladimir Černý; Josep Comin-Colet; Marisa G Crespo-Leiro; Juan F Delgado; István Édes; Alexander A Eremenko; Dimitrios Farmakis; Francesco Fedele; Cândida Fonseca; Sonja Fruhwald; Massimo Girardis; Fabio Guarracino; Veli-Pekka Harjola; Matthias Heringlake; Antoine Herpain; Leo M A Heunks; Tryggve Husebye; Višnja Ivancan; Kristjan Karason; Sundeep Kaul; Matti Kivikko; Janek Kubica; Josep Masip; Simon Matskeplishvili; Alexandre Mebazaa; Markku S Nieminen; Fabrizio Oliva; Julius G Papp; John Parissis; Alexander Parkhomenko; Pentti Põder; Gerhard Pölzl; Alexander Reinecke; Sven-Erik Ricksten; Hynek Riha; Alain Rudiger; Toni Sarapohja; Robert H G Schwinger; Wolfgang Toller; Luigi Tritapepe; Carsten Tschöpe; Gerhard Wikström; Dirk von Lewinski; Bojan Vrtovec; Piero Pollesello Journal: J Cardiovasc Pharmacol Date: 2020-07 Impact factor: 3.105
Authors: Zoltán Papp; Piergiuseppe Agostoni; Julian Alvarez; Dominique Bettex; Stefan Bouchez; Dulce Brito; Vladimir Černý; Josep Comin-Colet; Marisa G Crespo-Leiro; Juan F Delgado; Istvan Édes; Alexander A Eremenko; Dimitrios Farmakis; Francesco Fedele; Cândida Fonseca; Sonja Fruhwald; Massimo Girardis; Fabio Guarracino; Veli-Pekka Harjola; Matthias Heringlake; Antoine Herpain; Leo Ma Heunks; Tryggve Husebye; Višnja Ivancan; Kristjan Karason; Sundeep Kaul; Matti Kivikko; Janek Kubica; Josep Masip; Simon Matskeplishvili; Alexandre Mebazaa; Markku S Nieminen; Fabrizio Oliva; Julius-Gyula Papp; John Parissis; Alexander Parkhomenko; Pentti Põder; Gerhard Pölzl; Alexander Reinecke; Sven-Erik Ricksten; Hynek Riha; Alain Rudiger; Toni Sarapohja; Robert Hg Schwinger; Wolfgang Toller; Luigi Tritapepe; Carsten Tschöpe; Gerhard Wikström; Dirk von Lewinski; Bojan Vrtovec; Piero Pollesello Journal: Card Fail Rev Date: 2020-07-08