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

BackgroundThe 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.MethodsA sub study analysis of patients >18years 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 mu gmin(-1) followed by a constant infusion of 0.025 mu gmin(-1)) (exenatide group) or iv insulin therapy (control group) for blood glucose control (target range 100-139mgdl(-1)) during the first 48h 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 24h 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.ResultsFinally, 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] mu gl(-1) versus 2.64 [1.29-3.85] mu gl(-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 72h in the ICU was 6.34 [1.36-10.90] versus 5.04 [2.39-7.18] mu gl(-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).ConclusionsPostoperative 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