Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction

Abstract

In patients with STEMI undergoing pPCI, administration of exenatide at the time of reperfusion increases myocardial salvage.

Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial

“…31,32 Further cardioprotective effects, by means of increased coronary flow, 29 reduced myocardial infarct size, 33 and improved left ventricular function, have also been suggested by animal data. 30,34 Human mechanistic studies are consistent with these findings demonstrating an improvement in flow-mediated vasodilation in the postprandial state, 13 reduced infarct size in patients with ST-segment elevation myocardial infarction, 12,14 and an improvement in left ventricular ejection fraction in patients with heart failure. 35 These data together justify the conduct of a large-scale, adequately powered outcome trial testing for the superiority of a diabetes treatment regimen containing once-weekly exenatide on cardiovascular outcomes.…”

“…[7][8][9][10][11] Mechanistic data suggest that exenatide can improve cardiac function in patients with chronic heart failure, 12 improve endothelial dysfunction, 13 and reduce infarct size after ST-segment elevation myocardial infarction. 12,14 A patient-level integrated meta-analysis showed no evidence for increased cardiovascular disease risk with use of exenatide in 6 subjects with T2DM, 15 while a retrospective analysis of a medical and pharmaceutical insurance claims database found a lower relative cardiovascular disease risk associated with exenatide treatment than with other glucose-lowering drugs. 16 A small increase in heart rate has been observed with GLP-1 receptor agonists, which appears to be a class effect.…”

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…”

A new era in the management of type 2 diabetes: Is cardioprotection at long last a reality?

“…Findings from our laboratory demonstrated for the first time that the administration of either GLP-1 native peptide or the DPP-4 inhibitor protects against myocardial IRI in the isolated rat heart model through a mechanism not driven by the stimulation of insulin secretion, but by the activation of intracellular prosurvival kinases cascades [4]. Subsequently, Lonborg et al showed that the infusion of exenatide, a GLP-1analogue, prior to primary percutaneous coronary intervention reduces myocardial infarct size patients presenting with ST-segment elevation myocardial infarction [5].…”