Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction: The EXAMI study

Bernink, Flip J.P.; Timmers, Leo; Diamant, Michaëla; Scholte, Martijn; Beek, Aernout M.; Kamp, Otto; Marques, Koen M.; Denham, Robert N.; Chen, Weena J.Y.; Doevendans, Pieter A.; Rossum, Albert C. van; Royen, Niels van; Horrevoets, Anton J.G.; Appelman, Yolande

doi:10.1016/j.ijcard.2012.09.204

Cited by 38 publications

(25 citation statements)

References 9 publications

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“…Kristensen et al 29 found that liraglutide has a neutral effect on myocardial infarct size in a porcine ischemia-reperfusion model. A negative result with exenatide was also found in Bernink et al's 30 study. But in patients with STEMI, adjunctive exenatide therapy with pPCI was associated with a reduction in infarct size and improved subclinical LV function.…”

Section: Previous Researchsupporting

confidence: 66%

Effects of Liraglutide on Reperfusion Injury in Patients With ST-Segment–Elevation Myocardial Infarction

Chen

Tian

et al. 2016

Circ: Cardiovascular Imaging

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A cute ST-segment-elevation myocardial infarction (STEMI) is a leading cause of mortality and morbidity. Primary percutaneous coronary intervention (pPCI) is currently the most effective treatment strategy for STEMI. 1 However, acute restoration of myocardial blood flow may in itself jeopardize the cardiomyocytes. This phenomenon, known as reperfusion injury, may account for as much as 50% of the final myocardial infarct size, 2 a major determinant of the prognosis in patients with STEMI. 3 To date, few drugs have been shown to protect the heart during reperfusion. See Editorial by Flather See Clinical PerspectiveElevation of blood glucose is a common metabolic disorder among patients with acute myocardial infarction (AMI) and is associated with an adverse prognosis.5 Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates plasma glucose. GLP-1 may have antioxidant and anti-inflammatory properties and protect endothelial function. 6 Experimental studies have also revealed that GLP-1 or its analogs protect against reperfusion injury in pigs. 7 Liraglutide, a GLP-1 analog, was reported to reduce infarct size and improve cardiac output in normal and diabetic mice. 8 Several studies have shown that exenatide (another GLP-1 analog) protects against ischemia-reperfusion injury and reduces infarct size in patients with STEMI. 9,10 In our previous study, liraglutide could improve left ventricular (LV) function and reduce no-reflow in patients with AMI.11 No-reflow after AMI is an important predictor of infarct size and clinical outcome.12 However, the effects of liraglutide on infarct size in STEMI patients remain unclear. The aim of this study was to investigate the effects of liraglutide on myocardial salvage and infarct size using cardiac magnetic resonance (CMR) methods.Background-Liraglutide, a glucagon-like peptide-1 analog, was reported to reduce reperfusion injury in mice. We planned to evaluate the effects of liraglutide on reperfusion injury in patients with acute ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results-A total of 96 patients with ST-segment-elevation myocardial infarction undergoing emergency primary percutaneous coronary intervention were randomized to receive either subcutaneous liraglutide or placebo. Study treatment was commenced 30 minutes before intervention (1.8 mg) and maintained for 7 days after the procedure (0.6 mg for 2 days, 1.2 mg for 2 days, followed by 1.8 mg for 3 days). The salvage index was calculated from myocardial area at risk, measured during the index admission (35±12 hours), and final infarct size measured at 91±5 days after primary percutaneous coronary intervention by cardiac magnetic resonance. At 3 months, the primary end point, a higher salvage index was found in the liraglutide group than in the placebo group in 77 patients evaluated with cardiac magnetic resonance (0.66±0.14 versus 0.55±0.15; P=0.001). The final infarct size was lower in the liraglutide group than that in the placebo ...

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Section: Previous Researchsupporting

confidence: 66%

Effects of Liraglutide on Reperfusion Injury in Patients With ST-Segment–Elevation Myocardial Infarction

Chen

Tian

et al. 2016

Circ: Cardiovascular Imaging

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“…6 Their post hoc analysis 8 showed exenatide treatment was associated with a 30% decrease in final infarct size in patients with short system delay (≤132 minutes). In addition, Bernink et al 22 reported that 5 μg loading and 72-hour continuous intravenous infusion (20 μg/24 hours) of exenatide showed a trend toward a smaller infarction size but not significant difference. One important difference compared with previous studies is administrating dose and route of exenatide.…”

Section: Discussionmentioning

confidence: 99%

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

Woo

Kim

et al. 2013

ATVB

190

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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...

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“…Exogenous administration of a GLP-1 receptor agonist, such as exendin-4, has been shown to have certain direct beneficial effects on the cardiovascular system [7][8][9] , such as protection against ischemia [10] and improvement of left ventricular performance after myocardial infarction [11,12] . Several other studies have reported that exendin-4 can also affect fatty www.nature.com/aps Ma GF et al Acta Pharmacologica Sinica npg acids effusing into atherosclerotic lesions [11,13] .…”

Section: Introductionmentioning

confidence: 99%

Exendin-4 ameliorates oxidized-LDL-induced inhibition of macrophage migration in vitro via the NF-κB pathway

Chen

Yin

et al. 2013

Acta Pharmacol Sin

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Aim: To investigate the effects of the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 on oxidized low-density lipoprotein (ox-LDL)-induced inhibition of macrophage migration and the mechanisms underlying the effects of exendin-4. Methods: Primary peritoneal macrophages were extracted from the peritoneal cavity of mice treated with 3% thioglycollate (2 mL, ip). Migration of the macrophages was examined using a cell migration assay. Macrophage migration-related factors including leptin-like ox-LDL receptor (LOX-1), cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin-1 (IL-1)β, matrix metalloproteinase-2 (MMP-2), intercellular adhesion molecule (ICAM)-1 and macrophage migration inhibitory factor (MIF) were measured using semiquantitative RT-PCR. Expression of MIF and ICAM-1 proteins was examined with ELISA. Gelatin zymography was used to evaluate the activity of MMP-9. Activation of the NF-κB pathway was determined by confocal laser scanning microscopy. Results: Treatment of the macrophages with ox-LDL (50 μg/mL) markedly suppressed the macrophage migration. Furthermore, ox-LDL treatment substantially increased the expression of the macrophage migration-related factors, the activity of MMP-9 and the translocation of the NF-κB p65 subunit. These effects of ox-LDL were significantly ameliorated by pretreatment with the specific NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (100 μmol/L). These effects of ox-LDL were also significantly ameliorated by pretreatment with exendin-4 (25 and 50 nmol/L). Conclusion: Exendin-4 ameliorates the inhibition of ox-LDL on macrophage migration in vitro, via suppressing ox-LDL-induced expression of ICAM-1 and MIF, which is probably mediated by the NF-κB pathway.

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Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction: The EXAMI study

Cited by 38 publications

References 9 publications

Effects of Liraglutide on Reperfusion Injury in Patients With ST-Segment–Elevation Myocardial Infarction

Effects of Liraglutide on Reperfusion Injury in Patients With ST-Segment–Elevation Myocardial Infarction

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

Exendin-4 ameliorates oxidized-LDL-induced inhibition of macrophage migration in vitro via the NF-κB pathway

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