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)

被引:415
作者
Moiseyev, VS
Poder, P
Andrejevs, N
Ruda, MY
Golikov, AP
Lazebnik, LB
Kobalava, ZD
Lehtonen, LA
Laine, T
Nieminen, MS
Lie, KI
机构
[1] Univ Helsinki, Cent Hosp, Dept Internal Med, Div Cardiol, Helsinki 00029, Finland
[2] Russian Univ Peoples Friendship, Hosp 64, Moscow, Russia
[3] Orion Pharma, Res Ctr, Espoo, Finland
[4] Latvian Med Acad, P Stradins Res & Teaching Hosp, Riga, Latvia
[5] Cardiol Res Ctr, AL Myasnikov Cardiol Inst, Moscow 121552, Russia
[6] Sklifosovsky Res Inst Emergency Med, Cardiol Clin, Moscow, Russia
[7] Russian Med Acad Postgrad Training, Dept Gerontol & Geriatr, Moscow, Russia
[8] Univ Helsinki, Dept Clin Pharmacol, FIN-00014 Helsinki, Finland
[9] Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands
关键词
left ventricular failure; myocardial infarction; levosimendan; hypotension; ischaemia; mortality;
D O I
10.1053/euhj.2001.3158
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (0.1-0.4 mug.kg(-1).min(-1)) or placebo were administered intravenously for 6 h 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 6 h infusion (2.0% vs 5.9%; P=0.033) and over 24 h (4.0% vs 88%; 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 0.1-0.2 mug.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.
引用
收藏
页码:1422 / 1432
页数:11
相关论文
共 38 条
[11]   Prognostic importance of myocardial ischemia detected by ambulatory monitoring early after acute myocardial infarction [J].
Gill, JB ;
Cairns, JA ;
Roberts, RS ;
Costantini, L ;
Sealey, BJ ;
Fallen, EF ;
Tomlinson, CW ;
Gent, M .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (02) :65-70
[12]   EFFECTS OF DOBUTAMINE IN PATIENTS WITH ACUTE MYOCARDIAL-INFARCTION [J].
GILLESPIE, TA ;
AMBOS, HD ;
SOBEL, BE ;
ROBERTS, R .
AMERICAN JOURNAL OF CARDIOLOGY, 1977, 39 (04) :588-594
[13]   TROPONIN C-MEDIATED CALCIUM SENSITIZATION INDUCED BY LEVOSIMENDAN DOES NOT IMPAIR RELAXATION [J].
HAIKALA, H ;
NISSINEN, E ;
ETEMADZADEH, E ;
LEVIJOKI, J ;
LINDEN, IB .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1995, 25 (05) :794-801
[14]   Comparative efficacy of short-term intravenous infusions of milrinone and dobutamine in acute congestive heart failure following acute myocardial infarction [J].
Karlsberg, RP ;
DeWood, MA ;
DeMaria, AN ;
Berk, MR ;
Lasher, KP .
CLINICAL CARDIOLOGY, 1996, 19 (01) :21-30
[15]   PROGNOSIS OF ACUTE MYOCARDIAL-INFARCTION IN DIABETIC AND NONDIABETIC PATIENTS [J].
KARLSON, BW ;
HERLITZ, J ;
HJALMARSON, A .
DIABETIC MEDICINE, 1993, 10 (05) :449-454
[16]   Levosimendan, a new positive inotropic drug, decreases myocardial infarct size via activation of KATP channels [J].
Kersten, JR ;
Montgomery, MW ;
Pagel, PS ;
Warltier, DC .
ANESTHESIA AND ANALGESIA, 2000, 90 (01) :5-11
[17]   INTERMITTENT, AMBULATORY DOBUTAMINE INFUSIONS IN PATIENTS WITH SEVERE CONGESTIVE-HEART-FAILURE [J].
KRELL, MJ ;
KLINE, EM ;
BATES, ER ;
HODGSON, JM ;
DILWORTH, LR ;
LAUFER, N ;
VOGEL, RA ;
PITT, B .
AMERICAN HEART JOURNAL, 1986, 112 (04) :787-791
[18]   Cardiac responses to calcium sensitizers and isoproterenol in intact guinea pig hearts - Effects on cyclic AMP levels, protein phosphorylation, myoplasmic calcium concentration, and left ventricular function [J].
Kristof, E ;
Szigeti, G ;
Papp, Z ;
Bodi, A ;
Facsko, A ;
Kovacs, L ;
Papp, JG ;
Kranias, EG ;
Edes, I .
CARDIAC SARCOPLASMIC RETICULUM FUNCTION AND REGULATION OF CONTRACTILITY, 1998, 853 :316-319
[19]   The effects of levosimendan on [Ca2+]i in guinea-pig isolated ventricular myocytes [J].
Lancaster, MK ;
Cook, SJ .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1997, 339 (01) :97-100
[20]   Levosimendan: a parenteral calcium-sensitising drug with additional vasodilatory properties [J].
Lehtonen, LA .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2001, 10 (05) :955-970