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

摘要

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. 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. 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). Postoperative iv exenatide did not provide any additional cardioprotective effect compared to iv insulin in low-risk patients undergoing scheduled CABG surgery.