Levosimendan in acute heart failure following primary percutaneous coronary intervention-treated acute ST-elevation myocardial infarction. Results from the LEAF trial: a randomized, placebo-controlled study

Eur J Heart Fail. 2013 May;15(5):565-72. doi: 10.1093/eurjhf/hfs215. Epub 2013 Jan 2.

Abstract

Aims: The calcium sensitizer levosimendan may counteract stunning after reperfusion of ischaemic myocardium, but no randomized placebo-controlled trials exist regarding its use in PCI-treated ST-segment elevation infarction (STEMI). We evaluated the efficacy and safety of levosimendan in patients with a primary PCI-treated STEMI complicated by symptomatic heart failure (HF).

Methods and results: A total of 61 patients developing clinical signs of HF within 48 h after a primary PCI-treated STEMI (including cardiogenic shock) were randomized double-blind to a 25 h infusion of levosimendan or placebo. The primary endpoint was change in wall motion score index (WMSI) from baseline to day 5 measured by echocardiography. There was a significantly larger improvement in WMSI from baseline to day 5 in the levosimendan group compared with placebo (from 1.94 ± 0.20 to 1.66 ± 0.31 vs. 1.99 ± 0.22 to 1.83 ± 0.26, respectively, P = 0.031). There were significantly more episodes of hypotension during study drug infusion in the levosimendan group (67% vs. 36%, P = 0.029), but no significant difference in blood pressure at the end of infusion or in use of vasopressors. No significant between-group differences in changes in NT-proBNP levels, clinical composite score, frequency of atrial fibrillation or ventricular arrhythmia, infarct size at 6 weeks, or new clinical events up to 6 months were found. One and four patients died in the levosimendan and placebo group, respectively.

Conclusions: Levosimendan treatment improved contractility in post-ischaemic myocardium in patients with PCI-treated STEMI complicated by HF. The treatment was well tolerated, without any increase in arrhythmias.

Trial registration: ClinicalTrials.gov NCT00324766.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Cardiotonic Agents / adverse effects
  • Cardiotonic Agents / therapeutic use*
  • Double-Blind Method
  • Echocardiography
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Hydrazones / adverse effects
  • Hydrazones / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Contraction / drug effects
  • Myocardial Infarction / drug therapy*
  • Norway
  • Percutaneous Coronary Intervention
  • Pyridazines / adverse effects
  • Pyridazines / therapeutic use*
  • Simendan
  • Treatment Outcome

Substances

  • Cardiotonic Agents
  • Hydrazones
  • Pyridazines
  • Simendan

Associated data

  • ClinicalTrials.gov/NCT00324766