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).
OBJECTIVE
To evaluate the safety and efficacy of levosimendan in patients with left ventricular failure complicating acute myocardial infarction.


RESULTS
Levosimendan at different doses (0.1-0.4 microg x kg(-1) x 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
s Levosimendan at doses 0.1-0.2 microg x kg(-1) x 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.
Hospital No. 64, Russian University of People's Friendship, Moscow, Russia.
V S
VS
Moiseyev
P
P
Põder
N
N
Andrejevs
M Y
MY
Ruda
A P
AP
Golikov
L B
LB
Lazebnik
Z D
ZD
Kobalava
L A
LA
Lehtonen
T
T
Laine
M S
MS
Nieminen
K I
KI
Lie
D000208:Acute Disease; D000368:Aged; D000704:Analysis of Variance; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004341:Drug Evaluation; D023381:Endpoint Determination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006801:Humans; D006835:Hydrazones / Q000009:adverse effects / Q000627:therapeutic use*; D007022:Hypotension / Q000209:etiology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D011446:Prospective Studies; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D012449:Safety; D000077464:Simendan; D016019:Survival Analysis; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan