Journal Article

Impact of intravenous exenatide infusion for perioperative blood glucose control on myocardial ischemia-reperfusion injuries after coronary artery bypass graft surgery: sub study of the phase II/III ExSTRESS randomized trial

Barrucand, Benoit, Besch, Guillaume, Samain, Emmanuel, Salomon du Mont, Lucie, Chocron, Sidney, Ben-Said, Xavier, Vettoretti, Lucie, Pili-Floury, Sebastien, Perrotti, Andrea, Baltres, Maude, Flicoteaux, Guillaume, Puyraveau, Marc

2018

Overview

Background The aim of the study was to investigate whether intravenous (iv) infusion of exenatide, a synthetic GLP-1 receptor agonist, could provide a protective effect against myocardial ischemia-reperfusion injury after coronary artery bypass graft (CABG) surgery. Methods A sub study analysis of patients > 18 years admitted for elective CABG and included in the ExSTRESS trial was conducted. Patients were randomized to receive either iv exenatide (1-h bolus of 0.05 µg min −1 followed by a constant infusion of 0.025 µg min −1 ) (exenatide group) or iv insulin therapy (control group) for blood glucose control (target range 100–139 mg dl −1 ) during the first 48 h after surgical incision. All serum levels of troponin I measured during routine care in the Cardiac Surgery ICU were recorded. The primary outcome was the highest value of plasma concentration of troponin I measured between 12 and 24 h after ICU admission. The proportion of patients presenting an echocardiographic left ventricular ejection fraction (LVEF) > 50% at the follow-up consultation was compared between the two groups. Results Finally, 43 and 49 patients were analyzed in the control and exenatide groups, respectively {age: 69 [61–76] versus 71 [63–75] years; baseline LVEF < 50%: 6 (14%) versus 16 (32%) patients; on-pump surgery: 29 (67%) versus 33 (67%) patients}. The primary outcome did not significantly differ between the two groups (3.34 [1.06–6.19] µg l −1 versus 2.64 [1.29–3.85] µg l −1 in the control and exenatide groups, respectively; mean difference (MD) [95% confidence interval (95% CI)] 0.16 [− 0.25; 0.57], p = 0.54). The highest troponin value measured during the first 72 h in the ICU was 6.34 [1.36–10.90] versus 5.04 [2.39–7.18] µg l −1 , in the control and exenatide groups respectively (MD [95% CI] 0.20 [− 0.22; 0.61], p = 0.39). At the follow-up consultation, 5 (12%) versus 8 (16%) patients presented a LVEF < 50% in the control and in the exenatide groups respectively (relative risk [95% CI] 0.68 [0.16; 2.59], p = 0.56). Conclusions Postoperative iv exenatide did not provide any additional cardioprotective effect compared to iv insulin in low-risk patients undergoing scheduled CABG surgery. Trial registration ClinicalTrials.gov Identifier NCT01969149, date of registration: January 7th, 2015; EudraCT No. 2009-009254-25 A, date of registration: January 6th, 2009

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Aged / Angiology / Biomarkers - blood / Blood glucose / Blood Glucose - drug effects / Blood Glucose - metabolism / Calcium-binding protein / Cardiology / Cardioprotective effects / Coronary artery / Coronary artery bypass / Coronary Artery Bypass - adverse effects / Coronary vessels / Diabetes / Exenatide / Exenatide - administration & dosage / Exenatide - adverse effects / Female / France / GLP-1 receptor agonists / Glucagon-like peptide 1 / Glucose / Heart / Heart attacks / Heart surgery / Humans / Hypoglycemic Agents - administration & dosage / Hypoglycemic Agents - adverse effects / Incretins / Incretins - administration & dosage / Incretins - adverse effects / Infusions, Intravenous / Injuries / Insulin / Insulin resistance / Intravenous administration / Ischemia / Kinases / Male / Medicine / Medicine & Public Health / Middle Aged / Myocardial ischemia / Myocardial reperfusion injury / Myocardial Reperfusion Injury - blood / Myocardial Reperfusion Injury - diagnosis / Myocardial Reperfusion Injury - etiology / Myocardial Reperfusion Injury - prevention & control / Original Investigation / Patients / Peptides / Proteins / Quality of life / Registration / Reperfusion / Risk Factors / Rodents / Serum levels / Stroke Volume - drug effects / Studies / Time Factors / Treatment Outcome / Troponin / Troponin I / Troponin I - blood / Veins & arteries / Ventricle / Ventricular Function, Left - drug effects