Exenatide Reduces Final Infarct Size in Patients With ST-Segment–Elevation Myocardial Infarction and Short-Duration of Ischemia

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 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 (Pϭ0.006). In the patients with system delay Ͼ132 minutes (nϭ74) no difference was observed in infarct size expressed as grams (Pϭ0.49) or percentage (Pϭ0.46). 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 (Pϭ0.018). 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. (Circ Cardiovasc Interv. 2012;5:288-295.)

Impact of Acute Hyperglycemia on Myocardial Infarct Size, Area at Risk, and Salvage in Patients With STEMI and the Association With Exenatide Treatment: Results From a Randomized Study

“…In a previously published proof-of-concept study (30,31) on patients with STEMI and thrombolysis in myocardial infarction (TIMI) grade 0 or 1 flow before primary PCI, we demonstrated a cardioprotective effect of exenatide. Exenatide is a glucagon-like peptide analog that is known to increase insulin secretion and cellular glucose uptake, and subsequently reduce the level of blood glucose (32).…”

Modulation of Glucagon-like Peptide-1 (GLP-1) Potency by Endocannabinoid-like Lipids Represents a Novel Mode of Regulating GLP-1 Receptor Signaling

“…We probed the potential conformation of GLP-1(7-36) amide based on its susceptibility to trypsin digestion. The two trypsin cleavage products of GLP-1 amide are an inactive GLP-1 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) and a partially active GLP-1(7-34) (Fig. 8A) (32).…”

“…Mice deficient in GLP-1R expression or with blunted GLP-1R function show impairment of physiologic features not limited to glucose homeostasis but also including learning and memory (4). Clinical trials targeting GLP-1 signaling to treat non-metabolic diseases include those for psoriasis, heart disease, and neurodegenerative diseases (5)(6)(7). Despite encouraging outcomes with GLP-1 analogs in reducing myocardial infarct size in acute coronary occlusion (7) and improving clinical symptoms in patients with Parkinson disease (5), the mechanisms of physiological regulation of GLP-1R signaling beyond energy homeostasis remain largely unknown.…”

Metformin and Myocardial Injury in Patients With Diabetes and ST‐Segment Elevation Myocardial Infarction: A Propensity Score Matched Analysis

“…In a randomized double‐blind placebo‐controlled trial investigating the effect of metformin compared with glipizide on cardiovascular outcomes in patients with type 2 diabetes and CVD, metformin treatment led to a significantly lower number of major cardiovascular events compared with glipizide at 5 years (7 versus 14 deaths, respectively) 25. The GLP‐1 receptor agonist exenatide has been demonstrated to be cardioprotective in both animal studies26 and clinical trials 27, 28, 29. Conversely, sulphonylurea antidiabetic drugs seem to disrupt cardioprotection through inhibition of ATP‐dependent potassium channels 30…”