THE GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST EXENATIDE IS SAFE AND MAY BE CARDIOPROTECTIVE IN ACUTE MYOCARDIAL INFARCTION: THE EXAMI PHASE L TRIAL

.Reperfusion limits myocardial necrosis, however induces reperfusion injury leading to additional necrosis and apoptosis. Glucagon Like Peptide-1 (GLP-1), an incretin hormone, has anti-apoptotic properties and proved to be cardioprotective in experimental studies. This pilot study assessed the safety and feasibility of the GLP-1 receptor agonist exenatide in patients with acute MI undergoing primary PCI. Methods: Seventy-one non-diabetic patients with acute MI undergoing primary PCI were randomized to placebo or exenatide 5μg bolus administered in 30 minutes prior to PCI, followed by continuous infusion of 20μg/ 24 hours for 72 hours. Blood samples were obtained including enzymatic infarct size and glucose levels. Magnetic resonance imaging and echocardiography were conducted 3-5 days and 4 months post MI for measurements including infarct size, cardiac function and myocardial salvage index (MSI), a predictor for mortality and major adverse cardiac events. Results: Forty out of 71 randomized patients completed the full protocol. Exclusion was mainly due to angiographic criteria. Patient characteristics were well balanced between the groups. An equal amount of hypo- and hyperglycemic episodes (glucose 10 mmol/L) were observed in both groups. No deaths, CABG or re-infarction occurred during the 4-month follow-up. Although more patients in the exenatide group experienced nausea (58% v 20%, p = 0.015), no decrease or cessation of exenatide was required. Infarct size, cardiac function and MSI at 4 months did not differ signiicantly. However, a trend towards a higher MSI was seen in patients with TIMI 0 and 1 low receiving exenatide (0.65 ± 0.14 (n = 12) v 0.53 ± 0.17 (n = 11), p = 0.09). Conclusions: We demonstrated that administering exenatide in patients with acute MI undergoing primary PCI is feasible and safe. Although not powered for this analysis, Exami phase l seems to show a trend towards a higher MSI in the exenatide group. A large randomized placebo controlled study is required to assess the eficacy of exenatide on myocardial salvage.