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

Abstract

Abstract 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

Keywords

• Coronary artery bypass
• Exenatide
• Incretins
• Glucagon-like peptide 1
• Myocardial reperfusion injury
• Cardioprotective effects