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.
Moiseyev
V S
VS
Hospital No. 64, Russian University of People's Friendship, Moscow, Russia.
Põder
P
P
Andrejevs
N
N
Ruda
M Y
MY
Golikov
A P
AP
Lazebnik
L B
LB
Kobalava
Z D
ZD
Lehtonen
L A
LA
Laine
T
T
Nieminen
M S
MS
Lie
K I
KI
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