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

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: Cardioprotective effects; Coronary artery bypass; Exenatide; Glucagon-like peptide 1; Incretins; Myocardial reperfusion injury.

Figures

Fig. 1

Flow-chart of the study according to the CONSORT statement

Fig. 2

Troponin values in the cardiac surgery intensive care unit. Troponin0–12, troponin12–24, troponin24–48, and troponin48–72 are the highest troponin values measured respectively within 0–12 h, 12–24 h, 24–48 h, and 48–72 h after admission to the cardiac surgery intensive care unit. ap-value for repeated measures ANOVA. bNumber of troponin measurements for each timepoints in the control and in the exenatide groups

Fig. 3

Brain natriuretic peptide (BNP) values (a) and proportion of patients with BNP ≥ 200 pg/ml (b) in the cardiac surgery intensive care unit. BNP0–12, BNP12–24 and BNP24–48 are the highest BNP values measured within respectively 0–12 h, 12–24 h and 24–48 h after admission to the Cardiac Surgery Intensive Care Unit. ap-value for repeated measures ANOVA. bNumber of BNP measurements for each timepoints in the control and in the exenatide groups