RESUMO
AIMS: The aim of this study was to determine whether intermittent ambulatory treatment with levosimendan would improve functional capacity, quality of life, and event-free survival in patients with advanced heart failure. METHODS AND RESULTS: This was a prospective, randomized, double-blind, placebo-controlled, multicentre, parallel-group trial of pulsed infusions of levosimendan in 120 outpatients with advanced heart failure (EF ≤35%, NYHA class III or IV). The study was conducted at 11 centres in Austria, Greece, and Germany. Levosimendan (0.2 µg/kg/min) or placebo was administered for 6 h at 2-week intervals over 6 weeks, in addition to standard care therapy. The primary outcome was the proportion of patients with a ≥20% improvement in the 6 min walk test and a ≥15% score increase on the Kansas City Cardiomyopathy Questionnaire at the end of the 24-week study period. Secondary outcomes included event-free survival after 24 weeks. Analyses were performed on an intention-to-treat basis. The primary endpoint was reached in 19% of patients receiving levosimendan and 15.8% of patients receiving placebo (odds ratio 1.25; 95% confidence interval 0.44-3.59; P = 0.810). Cardiac death (four vs. one), heart transplants (two vs. one), and acute heart failure (14 vs. nine) were more frequent with placebo as compared with levosimendan. The incidence of side effects was comparable between groups. CONCLUSION: Intermittent ambulatory treatment with levosimendan in patients with advanced heart failure did not improve significantly functional capacity or quality of life as compared with placebo. An adequately powered, event-driven trial is warranted to enlarge on our findings. TRIAL REGISTRATION: NCT01065194.