Abstract
ObjectivesThis double blinded, placebo controlled randomized clinical trial studies the effect of exenatide on myocardial infarct size. The glucagon-like peptide-1 receptor agonist exenatide has possible cardioprotective properties during reperfusion after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Methods191 patients were randomly assigned to intravenous exenatide or placebo initiated prior to percutaneous coronary intervention using 10μg/h for 30min followed by 0.84μg/h for 72h. Patients with a previous myocardial infarction, Trombolysis in Myocardial Infarction flow 2 or 3, multi-vessel disease, or diabetes were excluded. Magnetic resonance imaging (MRI) was performed to determine infarct size, area at risk (AAR) (using T2-weighted hyperintensity (T2W) and late enhancement endocardial surface area (ESA)). The primary endpoint was of 4-month final infarct size, corrected for the AAR measured in the acute phase using MRI. ResultsAfter exclusion, 91 patients (age 57.4±10.1years, 76% male) completed the protocol. There were no baseline differences between groups. No difference was found in infarct size corrected for the AAR in the exenatide group compared to the placebo group (37.1±18.8 vs. 39.3±20.1%, p=0.662). There was also no difference in infarct size (18.8±13.2 vs. 18.8±11.3% of left ventricular mass, p=0.965). No major adverse cardiac events occurred during the in-hospital phase. ConclusionExenatide did not reduce myocardial infarct size expressed as a percentage of AAR in ST elevated myocardial infarction patients successfully treated with percutaneous coronary intervention.
Highlights
ST elevated myocardial infarction is a leading cause of mortality and morbidity, caused by acute occlusion of one or more of the epicardial coronary arteries
This is mediated by a multitude of factors that eventually culminate in loss of mitochondrial integrity and hypercontracture, leading to cardiomyocyte death [3]. This phenomenon is called reperfusion injury and contributes for up to 40% to the final myocardial infarct size [4], which is an important determinant of clinical outcome in patients with ST elevated myocardial infarction [5]
Exenatide therapy was shown to increase myocardial salvage [12] and decrease final infarct size [13] in ST elevated myocardial infarction patients successfully treated with percutaneous coronary intervention
Summary
ST elevated myocardial infarction is a leading cause of mortality and morbidity, caused by acute occlusion of one or more of the epicardial coronary arteries. This is mediated by a multitude of factors that eventually culminate in loss of mitochondrial integrity and hypercontracture, leading to cardiomyocyte death [3]. This phenomenon is called reperfusion injury and contributes for up to 40% to the final myocardial infarct size [4], which is an important determinant of clinical outcome in patients with ST elevated myocardial infarction [5]. Therapies to prevent reperfusion injury are of utmost importance
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