Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure. J Am Coll Cardiol HF

Abstract

Objectives: The purpose of this study was to evaluate the efficacy and safety of levosimendan, given intravenously to patients with acutely decompensated heart failure (ADHF). Background: Levosimendan, a positive inotropic drug with vasodilator effects has been reported to produce favorable effects on cardiac performance, symptoms, hospital stays and survival in patients with ADHF. The hemodynamic effects of levosimendan persist for many days after a 24 h infusion, due to a long-lived active metabolite. However, it is not clear that these hemodynamic effects translate into clinical benefits and improved outcomes. Methods: Two sequential trials were performed, the first to develop a new measure of efficacy in 100 patients, and the second to use this measure to evaluate levosimendan in an additional 600 patients. Patients admitted with ADHF received placebo or intravenous infusion of levosimendan for 24 h in addition to standard treatment. The primary endpoint was a composite that evaluated changes in clinical status during the first 5 days after randomization. Results: In the 600-patient trial, more levosimendan than placebo patients improved at all 3 pre-specified time points (6 h, 24 h, and 5 days), whereas fewer levosimendan patients experienced clinical worsening (p = 0.015). These differences were apparent, despite more frequent intensification of adjunctive therapy in the placebo group. Improvements in patient self-assessment and declines in B-type natriuretic peptide levels with levosimendan persisted for 5 days and were associated with reduced length of hospital stay (p = 0.009). However, levosimendan was associated with more frequent hypotension and cardiac arrhythmias during the infusion period and a numerically higher risk of death (p = 0.29). An excess risk of deaths in the levosimendan group was apparent as early as 5 days; was nominally significant at 14 days, and was largely seen in subgroups at highest risk of death before entry into the study (eg patients with systolic blood pressure 100 mmHg. Conclusions: In patients with ADHF, intravenous levosimendan provided rapid and durable symptomatic relief. However, levosimendan was associated with an increased risk of adverse cardiovascular events.