Levosimendan Treatment for Heart Failure: A Systematic Review and Meta-Analysis

Objective: Emerging studies suggest that administration of levosimendan therapy may be better than dobutamine or placebo in decompensated heart failure. The authors performed an updated meta-analysis of trials to obtain the best estimates of the efficacy and safety of levosimendan for the initial treatment of decompensated heart failure. Design: A meta-analysis. Setting: Hospitals. Participants: A total of 5,349 patients from 25 randomized controlled studies were included in the analysis. Interventions: None. Measurements and Main Results: The authors performed a meta-analysis of trials comparing levosimendan therapy with dobutamine or placebo in patients with decompensated heart failure. Twenty-five trials, involving 5,349 patients, were included. Two reviewers performed independent article review and study quality assessment. Data on overall mortality, early-term mortality, midterm mortality, long-term mortality, efficacy outcomes, and adverse events were collected. Mortality outcomes were according to follow-up duration: early term (<= 30-day), midterm (30-day to <= 6-month), and long term (>6-month). Levosimendan was compared with dobutamine or placebo, calculating pooled relatives risk (RRs) and associated 95% confidence intervals (Cis). A random-effects model was selected for meta-analysis if there was significant heterogeneity. Levosimendan significantly reduced total mortality (17.1% versus 20.8%; RR, 0.84; 95% CI, 0.75-0.94). Compared with dobutamine, levosimendan was associated with significant reduction in mortality at final follow-up (RR, 0.86; 95% CI, 0.76-0.97; I-2 = 7%; p = 0.02).Compared with placebo, levosimendan was associated with a nonsignificant trend in favor of placebo in mortality at final follow-up (11.6% versus 16.2%, RR, 0.75; 95% CI, 0.56-1.01; p = 0.06), but it was associated with a significant reduction in long-term mortality (RR, 0.34; 95%C1, 0.15-0.76; p = 0.009). Compared with dobutamine or placebo, levosimendan therapy was associated with improvements in hemodynamically- and echocardiographically-derived cardiac parameters. Levosimendan therapy increased the risks of extrasystoles (RR, 1.88; 95% CI, 1.26-2.81), hypotension (RR, 1.33; 95% CI, 1.151.53), and headache or migraine (RR, 1.94; 95% CI, 1.54-2.43) when compared with control therapy. Conclusions: As compared to placebo or dobutamine, levosimendan in patients with heart failure seemed to have hemodynamic and cardiac benefits. It reduced total mortality and was associated with an increased risk of cardiovascular adverse events. (C) 2015 Elsevier Inc. All rights reserved.