Meta-Analysis

Effect of glucagon-like peptide-1 receptor agonists administration during coronary artery bypass grafting: a systematic review and meta-analysis of randomized control trials

Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, T6G 2B7, Canada

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Nicholas Fialka

Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, T6G 2B7, Canada

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Ryaan EL-Andari

https://orcid.org/0000-0001-7146-4337

Division of Cardiac Surgery, Department of Surgery, University of Alberta, Edmonton, AB, T6G 2B7, Canada

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Jimmy JH Kang

Division of Cardiac Surgery, Department of Surgery, University of Alberta, Edmonton, AB, T6G 2B7, Canada

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Sabin J Bozso

Division of Cardiac Surgery, Department of Surgery, University of Alberta, Edmonton, AB, T6G 2B7, Canada

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Jeevan Nagendran

*Author for correspondence: Tel.: +1 780 492 7605;

E-mail Address: jeevan@ualberta.ca

https://orcid.org/0000-0002-2050-6717

Division of Cardiac Surgery, Department of Surgery, University of Alberta, Edmonton, AB, T6G 2B7, Canada

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Published Online:28 Mar 2023https://doi.org/10.2217/fca-2022-0093

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Abstract

Aim: To determine if glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can benefit patients receiving coronary artery bypass graft (CABG), GLP-1 RAs administration alongside standard insulin was compared with perioperative insulin alone. Materials & methods: All articles from Pubmed and Scopus databases that compared GLP-1 RA administration to insulin alone during CABG were included for meta-analysis. Short-term postoperative outcomes were analyzed between groups. Results: Average postoperative blood glucose levels significantly favored GLP-1 RA with a mean difference of -0.72 (p < 0.001). No other variables were significantly different between GLP-1 RA and insulin alone. Conclusion: GLP-1 RA is a safe option for perioperative care of CABG patients that can potentially improve postoperative outcomes of CABG patients by improving glycemic control and reducing hyperglycemic episodes.

Plain language summary

What is this article about? Coronary artery bypass graft (CABG) is a common surgery for patients who have blocked blood vessels in their heart preventing their heart from functioning properly. Compared with other treatment options, CABG has better long-term outcomes and chances of survival, especially for patients with diabetes. Some medications that lower blood sugar levels in patients with diabetes, are also well known to improve heart health in this population. Because of these benefits, the specific medication called GLP-1 RA, has been proposed as an option to improve outcomes of people receiving CABG surgery. What were the results? By taking a systematic approach, 1375 articles were screened to find seven trials that tested the comparison of GLP-1 RA versus a control of just insulin in CABG patients. Analyzing this data, CABG patients receiving GLP-1 RA had significantly lower blood sugar levels compared with patients getting the control. The GLP-1 RA group also, on average, had similar or lower levels of heart rate arrhythmias, events of critically low blood sugar and the need of serious interventions compared with the control group. What do the results of the study mean? These results demonstrate that GLP-1 RA have similar or improved outcomes compared with standard therapy alone, suggesting it as a safe option for CABG patients. By lowering blood sugar levels, GLP-1 RA could also decrease complication rates and improve patient management compared with standard therapy alone, since high blood sugar levels are correlated with increased complications and worse postoperation outcomes.

Tweetable abstract

GLP-1 RAs is a potentially beneficial perioperative medication for patients receiving coronary artery bypass grafting surgery by lowering postoperative glucose levels and demonstrating similar or lower levels of coronary artery bypass grafting; complications compared with insulin therapy alone. #research #heartsurgery #medication

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Jacobs JP, Shahian DM, D'agostino RS et al. The Society of Thoracic Surgeons National Database 2018 annual report. Ann. Thorac. Surg. 106, 1603–1611 (2018).
MedlineGoogle Scholar
2. Head SJ, Milojevic M, Daemen J et al. Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data. Lancet 391(10124), 939–948 (2018).
MedlineGoogle Scholar
3. Gaudino M, Hameed I, Farkouh ME et al. Overall and cause-specific mortality in randomized clinical trials comparing percutaneous interventions with coronary bypass surgery: a meta-analysis. JAMA Intern. Med. 180(12), 1638–1646 (2020).
MedlineGoogle Scholar
4. Giacoppo D, Colleran R, Cassese S et al. Percutaneous coronary intervention vs coronary artery bypass grafting in patients with left main coronary artery stenosis: a systematic review and meta-analysis. JAMA Cardiol. 2(10), 1079 (2017).
MedlineGoogle Scholar
5. Sá MPBO, Soares AF, Miranda RGA et al. CABG surgery remains the best option for patients with left maincoronary disease in comparison with PCI-DES: meta-analysis of randomized controlled trials. Brazilian J. Cardiovasc. Surg. 32(5), 408 (2017).
MedlineGoogle Scholar
6. El-Andari R, Bozso SJ, Fialka NM, Kang JJH, Nagendran J, Nagendran J. Coronary revascularization for patients with diabetes mellitus: a contemporary systematic review and meta-analysis. Ann. Surg. 275(6), 1058–1066 (2022). • Coronary artery bypass grafting patients with diabetes have improved for long-term mortality rates, incidence of revascularization, rates of myocardial infarction and readmission to hospital compared to patients with diabetes receiving percutaneous coronary intervention.
MedlineGoogle Scholar
7. d'Entremont MA, Yagi R, Salia SJS et al. The effect of diabetes on surgical versus percutaneous left main revascularization outcomes: a systematic review and meta-analysis. J. Cardiothorac. Surg. 17(1), 1–11 (2022).
MedlineGoogle Scholar
8. Xie Q, Huang J, Zhu K, Chen Q. Percutaneous coronary intervention versus coronary artery bypass grafting in patients with coronary heart disease and Type 2 diabetes mellitus: cumulative meta-analysis. Clin. Cardiol. 44(7), 899–906 (2021).
MedlineGoogle Scholar
9. Hawkes AL, Nowak M, Bidstrup B, Speare R. Outcomes of coronary artery bypass graft surgery. Vasc. Health Risk Manag. 2(4), 477 (2006).
MedlineGoogle Scholar
10. Adelborg K, Horváth-Puhó E, Schmidt M et al. Thirty-year mortality after coronary artery bypass graft surgery. Circ. Cardiovasc. Qual. Outcomes 10(5), e002708 (2017).
MedlineGoogle Scholar
11. Papazafiropoulou A, Pappas SI, Papadogiannis D, Tentolouris N. Cardiovascular effects of glucagon-like peptide 1. Mini Rev. Med. Chem. 11(1), 97–105 (2011).
Medline CASGoogle Scholar
12. Read PA, Khan FZ, Dutka DP. Cardioprotection against ischaemia induced by dobutamine stress using glucagon-like peptide-1 in patients with coronary artery disease. Heart 98(5), 408–413 (2012). •• Global left ventricular function was greater at peak stress during GLP-1 infusion compared with control, with beneficial effect predominantly seen in ischemic segments. Intravenous infusion of GLP-1 protects the heart from ischemic left ventricular dysfunction induced by dobutamine stress in patients with coronary artery disease.
Medline CASGoogle Scholar
13. Yeong T, Mai AS, Lim OZH et al. Can glucose-lowering medications improve outcomes in non-diabetic heart failure patients? A Bayesian network meta-analysis. ESC Hear. Fail. 9(2), 1338–1350 (2022).
MedlineGoogle Scholar
14. Gerstein HC, Colhoun HM, Dagenais GR et al. Dulaglutide and cardiovascular outcomes in Type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 394(10193), 121–130 (2019).
Medline CASGoogle Scholar
15. Lavalle-Cobo A, Masson W, Lobo M, Masson G, Molinero G. Glucagon-like peptide-1 receptor agonists and cardioprotective benefit in patients with Type 2 diabetes without baseline metformin: a systematic review and update meta-analysis. High Blood Press. Cardiovasc. Prev. 28(6), 605–612 (2021).
Medline CASGoogle Scholar
16. Meier JJ. GLP-1 receptor agonists for individualized treatment of Type 2 diabetes mellitus. Nat. Rev. Endocrinol. 8(12), 728–742 (2012).
Medline CASGoogle Scholar
17. Uccellatore A, Genovese S, Dicembrini I, Mannucci E, Ceriello A. Comparison review of short-acting and long-acting glucagon-like peptide-1 receptor agonists. Diabetes Ther. 6(3), 239 (2015).
Medline CASGoogle Scholar
18. Shyangdan DS, Royle P, Clar C, Sharma P, Waugh N, Snaith A. Glucagon-like peptide analogues for Type 2 diabetes mellitus. Cochrane Database Syst. Rev. 2011(10), CD006423 (2011).
MedlineGoogle Scholar
19. Papazafiropoulou A, Pappas SI, Papadogiannis D, Tentolouris N. Cardiovascular effects of glucagon-like peptide 1. Mini Rev. Med. Chem. 11(1), 97–105 (2010). •• Results suggest that GLP-1 have promising results in patients with heart failure, acute myocardial infarction and revascularization procedures in addition to the standard therapy. Administration of GLP-1 also has been shown to increases ejection fraction in acute myocardial infraction and reduces ischemia-reperfusion myocardial injury.
Google Scholar
20. Ravassa S, Zudaire A, Díez J. GLP-1 and cardioprotection: from bench to bedside. Cardiovasc. Res. 94(2), 316–323 (2012).
Medline CASGoogle Scholar
21. Eikelboom R, Amir T, Gupta S, Whitlock RP. Optimal medical therapy after coronary artery bypass grafting: a primer for surgeons. Curr. Opin. Cardiol. 36(5), 609–615 (2021). • Long-acting GLP-1 receptor agonists or SLGT-2 inhibitors should be used in all post-coronary artery bypass grafting patients with Type 2 diabetes.
MedlineGoogle Scholar
22. Yang X, Liang Z. Efficacy of liraglutide intervention in myocardial infarction. Herz 45(5), 461–467 (2018).
MedlineGoogle Scholar
23. Page MJ, Moher D, Bossuyt PM et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 372, n160 (2021).
MedlineGoogle Scholar
24. Page MJ, McKenzie JE, Bossuyt PM et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372, n71 (2021).
MedlineGoogle Scholar
25. Sterne JA, Hernán MA, Reeves BC et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 355, i4919 (2016).
MedlineGoogle Scholar
26. Guyatt GH, Oxman AD, Vist G et al. GRADE guidelines: 4. Rating the quality of evidence-study limitations (risk of bias). J. Clin. Epidemiol. 64(4), 407–415 (2011).
MedlineGoogle Scholar
27. Olivo SA, Macedo LG, Gadotti IC, Fuentes J, Stanton T, Magee DJ. Scales to assess the quality of randomized controlled trials: a systematic review. Phys. Ther. 88(2), 156–175 (2008).
MedlineGoogle Scholar
28. Besch G, Perrotti A, Salomon du Mont L et al. 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. Cardiovasc. Diabetol. 17(1), 140 (2018).
Medline CASGoogle Scholar
29. Besch G, Perrotti A, Mauny F et al. Clinical effectiveness of intravenous exenatide infusion in perioperative glycemic control after coronary artery bypass graft surgery a phase II/III randomized trial. Anesthesiology 127(5), 775–787 (2017).
Medline CASGoogle Scholar
30. Lipš M, Mráz M, Kloučková J et al. Effect of continuous exenatide infusion on cardiac function and peri-operative glucose control in patients undergoing cardiac surgery: a single-blind, randomized controlled trial. Diabetes Obes. Metab. 19(12), 1818–1822 (2017).
Medline CASGoogle Scholar
31. Hulst AH, Visscher MJ, Godfried MB et al. Liraglutide for perioperative management of hyperglycaemia in cardiac surgery patients: a multicentre randomized superiority trial. Diabetes Obes. Metab. 22(4), 557–565 (2019).
MedlineGoogle Scholar
32. Hulst AH, Visscher MJ, Cherpanath TGV et al. Effects of liraglutide on myocardial function after cardiac surgery: a secondary analysis of the randomised controlled GLOBE trial. J. Clin. Med. 9(3), 673 (2020).
Medline CASGoogle Scholar
33. Makino H, Tanaka A, Asakura K et al. Addition of low-dose liraglutide to insulin therapy is useful for glycaemic control during the peri-operative period: effect of glucagon-like peptide-1 receptor agonist therapy on glycaemic control in patients undergoing cardiac surgery (GLOLIA study). Diabet. Med. 36(12), 1621–1628 (2019).
Medline CASGoogle Scholar
34. Sokos GG, Bolukoglu H, German J et al. Effect of glucagon-like peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting. Am. J. Cardiol. 100(5), 824–829 (2007).
Medline CASGoogle Scholar
35. Besch G, Perrotti A, Salomon du Mont L et al. 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. Cardiovasc. Diabetol. 17(1), 1–11 (2018).
MedlineGoogle Scholar
36. Studer C, Sankou W, Penfornis A et al. Efficacy and safety of an insulin infusion protocol during and after cardiac surgery. Diabetes Metab. 36(1), 71–78 (2010).
Medline CASGoogle Scholar
37. Blaha J, Kopecky P, Matias M et al. Comparison of three protocols for tight glycemic control in cardiac surgery patients. Diabetes Care 32(5), 757 (2009).
MedlineGoogle Scholar
38. Ad N, Tran HA, Halpin L et al. Practice changes in blood glucose management following open heart surgery: from a prospective randomized study to everyday practice. Eur. J. Cardio-thoracic Surg. 47(4), 733–739 (2015).
MedlineGoogle Scholar
39. Galindo RJ, Fayfman M, Umpierrez GE. Perioperative management of hyperglycemia and diabetes in cardiac surgery patients. Endocrinol. Metab. Clin. North Am. 47(1), 203 (2018). •• Improved glycemic control in all cardiac surgery patients reduces perioperative complications including incidences of infection, adverse outcomes and death.
MedlineGoogle Scholar
40. Frioud A, Comte-Perret S, Nguyen S, Berger MM, Ruchat P, Ruiz J. Blood glucose level on postoperative day 1 is predictive of adverse outcomes after cardiovascular surgery. Diabetes Metab. 36(1), 36–42 (2010).
Medline CASGoogle Scholar
41. Levetan CS, Magee MF. Hospital management of diabetes. Endocrinol. Metab. Clin. North Am. 29(4), 745–770 (2000).
Medline CASGoogle Scholar
42. Nreu B, Dicembrini I, Tinti F, Sesti G, Mannucci E, Monami M. Major cardiovascular events, heart failure, and atrial fibrillation in patients treated with glucagon-like peptide-1 receptor agonists: an updated meta-analysis of randomized controlled trials. Nutr. Metab. Cardiovasc. Dis. 30(7), 1106–1114 (2020). • Meta-analysis demonstrating that GLP-1 RA does not increase the risk of atrial fibrillation in patients with diabetes taking the medication for glycemic control.
Medline CASGoogle Scholar

Vol. 19, No. 2

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History

Received 18 September 2022

Accepted 9 February 2023

Published online 28 March 2023

Published in print February 2023

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Author contributions

AR Watkins: Conceptualization, investigations, manuscript writing, data curation, analysis, finalizing of final draft. N Fialka: Conceptualization, investigations, manuscript writing, data curation, finalizing of final draft. R EL-Andari: Conceptualization, figure creation, manuscript editing, data curation, finalizing of final draft. JJH Kang: Conceptualization, manuscript editing, finalizing of final draft. SJ Bozso: Conceptualization, manuscript editing, finalizing of final draft. J Nagendran: Conceptualization, manuscript editing, data curation, finalizing of final draft, project supervision.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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