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

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 > 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.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] 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).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

Effects of Liraglutide on Myocardial Function After Cardiac Surgery: A Secondary Analysis of the Randomised Controlled GLOBE Trial

“…In the present study, the most statistically robust findings were also the higher heart rates observed in the liraglutide group. This effect has been consistently demonstrated in previous studies [16][17][18][19] and GLP-1 receptors have been found in the sinoatrial node [10,20,21]. Some authors have found GLP-1 RAs to induce vasodilation and microvascular recruitment, resulting in lower systemic vascular resistance [21] as well as an atrial natriuretic peptide-mediated reduction of systolic and diastolic blood pressures [4].…”

“…While we performed the first randomised trial using liraglutide in patients undergoing cardiac surgery [2], Besch et al randomised patients undergoing CABG to either a continuous exenatide infusion or insulin for glycaemic control [16]. Similar to our present study, the authors performed an analysis of cardiac outcomes and found no difference in postoperative troponin levels nor in the incidence of reduced left ventricular ejection fraction between treatment and control groups [17]. Of note, the primary outcome of this trial (time spent within the glycaemic target range) also did not reach a significant difference between groups [16].…”

Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis

“…It protects against acute liver injury in the mouse [57]. However, cardiovascular benefits have not been observed in studies of exenatide [13, 58]. In low-risk patients undergoing scheduled coronary artery bypass grafting surgery, postoperative intravenous exenatide provided no additional cardio-protective effect compared to intravenous insulin [58].…”

“…However, cardiovascular benefits have not been observed in studies of exenatide [13, 58]. In low-risk patients undergoing scheduled coronary artery bypass grafting surgery, postoperative intravenous exenatide provided no additional cardio-protective effect compared to intravenous insulin [58]. Therefore, it is still necessary to study the cardiovascular efficacy and safety profile of GLP-1 RAs so as to confirm their place in clinical practice.…”

Comparison of the effects of twice-daily exenatide and insulin on carotid intima-media thickness in type 2 diabetes mellitus patients: a 52-week randomized, open-label, controlled trial

“…Another study showed that the use of dipeptidyl peptidase-4 inhibitors were associated with a reduced risk of heart failure hospitalization compared to GLP-1RAs [24]. Moreover, postoperative exenatide did not provide any additional cardioprotective effect compared to intravenous insulin in coronary artery bypass grafting patients [25]. The effects of GLP-1RA on the cardiovascular risk are still controversial.…”