Copyright © 2002 by the European Society of Cardiology.
Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN)
a Hospital No. 64, Russian University of People's Friendship, Moscow, Russia
b Orion Pharma, Research Center, Espoo, Finland
c P. Stradin's Research and Teaching Hospital, Latvian Medical Academy, Riga, Latvia
d A.L. Myasnikov Institute of Cardiology, Cardiology Research Center, Moscow, Russia
e Cardiology Clinic, Sklifosovsky Research Institute for Emergency Medicine, Moscow, Russia
f Department of Gerontology and Geriatrics, Russian Medical Academy for Postgraduate Training, Moscow, Russia
g Department of Clinical Pharmacology, University of Helsinki, Finland
h Helsinki University Central Hospital, Cardiology Division, Helsinki, Finland
i Academic Medical Center, University of Amsterdam, The Netherlands
Received December 4, 2001; accepted December 12, 2001
Abstract
Aims To evaluate the safety and efficacy of levosimendan in patients with left ventricular failure complicating acute myocardial infarction.
Methods and Results Levosimendan at different doses (0·1–0·4µg.kg–1.min–1) or placebo were administered intravenously for 6h to 504 patients in a randomised, placebo-controlled, double-blind study. The primary end-point was hypotension or myocardial ischaemia of clinical significance adjudicated by an independent Safety Committee. Secondary end-points included risk of death and worsening heart failure, symptoms of heart failure and all-cause mortality. The incidence of ischaemia and/or hypotension was similar in all treatment groups (P=0·319). A higher frequency of ischaemia and/or hypotension was only seen in the highest levosimendan dose group. Levosimendan-treated patients experienced lower risk of death and worsening heart failure than patients receiving placebo, during both the 6h infusion (2·0% vs 5·9%; P=0·033) and over 24h (4·0% vs 8·8%; P=0·044). Mortality was lower with levosimendan compared with placebo at 14 days (11·7% vs 19·6%; hazard ratio 0·56 [95% CI 0·33–0·95];P =0·031) and the reduction was maintained at the 180-day retrospective follow-up (22·6% vs 31·4%; 0·67 [0·45-1·00],P =0·053).
Conclusions Levosimendan at doses 0·1–0·2µg.kg–1.min–1 did not induce hypotension or ischaemia and reduced the risk of worsening heart failure and death in patients with left ventricular failure complicating acute myocardial infarction. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.
Key Words: Left ventricular failure, myocardial infarction, levosimendan, hypotension, ischaemia, mortality
f2 Correspondence: Professor Markku S. Nieminen, MD, PhD, FACC, Helsinki University Central Hospital, Department of Internal Medicine, Cardiology Division, 00029, Haartmaninkatu 4, Helsinki, Finland.
f1 All investigators and study sites are listed in the Appendix.
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