Cardioprotective Effects of Exenatide in Patients With ST-Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Abstract

Objective-Experimental evidence suggests that exenatide, a glucagon-like peptide 1 receptor analogue, has significant cardiovascular protective effects in various conditions. We examined whether routine use of exenatide at the time of primary percutaneous coronary intervention would reduce infarct size in patients with ST-segment-elevation myocardial infarction. Approach and Results-Fifty-eight patients with ST-segment-elevation myocardial infarction and thrombolysis in myocardial infarction flow 0 were enrolled in the study and randomly assigned to receive either exenatide or placebo (saline) subcutaneously. Infarct size was assessed by measuring the release of creatine kinase-MB and troponin I during 72 hours and by performing cardiac magnetic resonance imaging at 1 month after infarction. Routine and speckle tracking echocardiography was performed at initial presentation and at 3 days and 6 months after primary percutaneous coronary intervention. The exenatide and control groups had similar results with respect to ischemia time, demographic characteristics, and ejection fraction before primary percutaneous coronary intervention. The releases of creatine kinase-MB and troponin I were significantly reduced in the exenatide group. In 58 patients evaluated with cardiac magnetic resonance, the absolute mass of delayed hyperenhancement was significantly reduced in the exenatide group as compared with the control group (12.8±11.7 versus 26.4±11.6 g; P<0.01). At 6 months, the exenatide group showed a significantly lower value of E/E′ with improved strain parameters. No significant adverse effects of exenatide administration were detected. Conclusions-In Woo et al Myocardial Protection of Exenatide in AMI 2253in patients with STEMI independent of diabetes mellitus and the safety/tolerability of this drug in an acute setting. To establish these issues, we conducted serial assessment of cardiac biomarkers, routine and speckle tracking echocardiography, and cardiac magnetic resonance imaging in patients with STEMI after performing primary percutaneous coronary intervention (pPCI). Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results Patient CharacteristicsBetween September 2009 and August 2011, we assessed eligibility for 127 consecutive patients with STEMI meeting the clinical eligibility criteria (Figure 1). Eleven patients were excluded from the study before randomization as a withdrawal of consent. After randomization, patients with impaired left ventricular (LV) systolic function (n=18), patients with thrombolysis in myocardial infarction flow grade 1, 2 or 3 on angiography (n=40) were also excluded. All remaining 58 patients completed the study protocol by performing the cardiac magnetic resonance study. No patients performed direct stenting, distal protecting devices, or glycoprotein IIb/IIIa administration. Successful PCI with drug-eluting stents was performed in all patients, and complete revascularization was achieved at a rate of 88%. During the 6-month follow-up, n...

Nonalcoholic fatty liver disease is independently associated with early left ventricular diastolic dysfunction in patients with type 2 diabetes

“…Moreover, it is also important to note that the use of hypoglycemic, lipidlowering and anti-hypertensive drugs was not significantly different between patients with and without NAFLD. Again, no patients were treated with pioglitazone or glucagon-like peptide-1 receptor agonists, which have been shown to reduce hepatic steatosis [1,9,25] and improve cardiac function [26,27]. Finally, our novel finding of a significant association between NAFLD and larger left atrial volume might also be of pathophysiological relevance in the explanation of recent observations documenting that type 2 diabetic patients with NAFLD are at risk of atrial fibrillation [28,29].…”

Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome

“…These drugs lower glucose levels by inhibiting the secretion of glucagon, promoting the release of insulin in response to hyperglycemia, slowing gastric emptying, and augmenting satiety. 14 On the basis of some evidence of cardioprotection in preliminary studies in animal models 15,16 and in pilot studies of myocardial ischemia 17,18 and heart failure in humans, 19 it was postulated 20,21 that in addition to improving glycemic control and promoting weight loss, GLP-1-receptor agonists may improve cardiovascular outcomes.…”

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…”