Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia

Circ Cardiovasc Interv. 2012 Apr;5(2):288-95. doi: 10.1161/CIRCINTERVENTIONS.112.968388. Epub 2012 Apr 10.

Abstract

Background: Exenatide has been demonstrated to be cardioprotective as an adjunct to primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction (STEMI). The aim of the post hoc analysis study was to evaluate the effect of exenatide in relation to system delay, defined as time from first medical contact to first balloon.

Methods and results: Patients with STEMI and Thrombolysis In Myocardial Infarction flow 0/1 were randomly assigned to intravenous exenatide or placebo continuous infusion. Study treatment was commenced 15 minutes before intervention and maintained for 6 hours after the procedure. The patients were stratified according to median system delay (132 minutes). Final infarct size and myocardial area at risk were measured by cardiovascular magnetic resonance. Among patients with a system delay ≤132 minutes (n=74), treatment with exenatide resulted in a smaller infarct size (9 grams [interquartile range (IQR), 4-13] versus 13 grams [IQR, 8-24], P=0.008, corresponding to 8% [IQR, 4-12] versus 11% [IQR, 7-17] of the left ventricle, P=0.015). In a regression analysis adjusting for myocardial area at risk the data points of the exenatide group lay significantly lower than for the placebo group (P=0.006). In the patients with system delay >132 minutes (n=74) no difference was observed in infarct size expressed as grams (P=0.49) or percentage (P=0.46). There was significant interaction between system delay (less than or equal to median versus greater than median) and treatment allocation in terms of infarct size (P=0.018).

Conclusions: In this post hoc analysis, exenatide treatment was associated with a 30% decrease in final infarct size in patients with short system delay, whereas no cardioprotective effect in patients with long system delay was seen. However, this finding must be confirmed in larger studies.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00835848.

Publication types

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

MeSH terms

  • Aged
  • Angioplasty*
  • Chemotherapy, Adjuvant
  • Coronary Vessels / surgery
  • Disease-Free Survival
  • Electrocardiography
  • Exenatide
  • Female
  • Heart / diagnostic imaging
  • Heart / drug effects*
  • Heart / physiopathology
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / surgery
  • Myocardium / pathology*
  • Peptides / administration & dosage*
  • Peptides / adverse effects
  • Radiography
  • Reperfusion Injury / etiology
  • Reperfusion Injury / prevention & control*
  • Venoms / administration & dosage*
  • Venoms / adverse effects
  • Warm Ischemia

Substances

  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Exenatide

Associated data

  • ClinicalTrials.gov/NCT00835848