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)

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 (0·1-0·4 μg . 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 6h infusion (2·0% vs 5·9%; P=0·033) and over 24 h (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 0·33-0·951; 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 μg . 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.