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)

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.