Effects of Sodium-Glucose Transporter 2 Inhibitors (SGLT2-I) in Patients With Ischemic Heart Disease (IHD) Treated by Coronary Artery Bypass Grafting via MiECC: Inflammatory Burden, and Clinical Outcomes at 5 Years of Follow-Up

Celestino Sardu; Massimo Massetti; Nicola Testa; Luigi Di Martino; Gaetano Castellano; Fabrizio Turriziani; Ferdinando Carlo Sasso; Michele Torella; Marisa De Feo; Gaetano Santulli; Giuseppe Paolisso; Raffaele Marfella

doi:10.3389/fphar.2021.777083

Effects of Sodium-Glucose Transporter 2 Inhibitors (SGLT2-I) in Patients With Ischemic Heart Disease (IHD) Treated by Coronary Artery Bypass Grafting via MiECC: Inflammatory Burden, and Clinical Outcomes at 5 Years of Follow-Up

Front Pharmacol. 2021 Nov 15:12:777083. doi: 10.3389/fphar.2021.777083. eCollection 2021.

Authors

Celestino Sardu^{1

2}, Massimo Massetti^{2

3}, Nicola Testa², Luigi Di Martino², Gaetano Castellano², Fabrizio Turriziani¹, Ferdinando Carlo Sasso¹, Michele Torella⁴, Marisa De Feo⁴, Gaetano Santulli^{5

6

7}, Giuseppe Paolisso^{1

8}, Raffaele Marfella^{1

8}

Affiliations

¹ Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy.
² Department of Cardiovascular and Arrhythmias, Campobasso, Italy.
³ Department of Cardio-thoracic Surgery, Catholic University of Sacred Heart, Rome, Italy.
⁴ Department of Cardiothoracic Surgery, University of Campania Luigi Vanvitelli, Naples, Italy.
⁵ Department of Advanced Biomedical Sciences, International Translational Research and Medical Education Academic Research Unit (ITME), Federico II University, Naples, Italy.
⁶ Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, Wilf Family Cardiovascular Research Institute, New York, NY, United States.
⁷ Department of Molecular Pharmacology, Fleischer Institute for Diabetes and Metabolism (FIDAM), Montefiore University Hospital, New York, NY, United States.
⁸ Mediterranea Cardiocentro, Naples, Italy.

Abstract

Introduction: Minimally invasive extracorporeal circulation (MiECC) reduced inflammatory burden, leading to best clinical outcomes in patients treated with coronary artery bypass grafting (CABG). Despite this, the patients with type 2 diabetes mellitus (T2DM) vs those without T2DM (non-T2DM) have a worse prognosis, caused by over-inflammation and modulated by sodium-glucose transporter 2 receptors. However, we evaluated the inflammatory burden and clinical outcomes in non-T2DM vs T2DM patients under sodium-glucose transporter 2 inhibitors (SGLT2-I users) vs non-SGLT2-I users at 5 years of follow-up post-CABG via MiECC. Materials and methods: In a multicenter study, we screened consecutive patients with indications to receive CABG. The study endpoints were the inflammatory burden (circulating serum levels of tumor necrosis factor-alpha (TNF-α), interleukin 1 and 6 (IL-1 and IL-6), C-reactive protein (CRP), and leucocytes count) and the clinical outcomes at follow-up of 5 years in non-T2DM vs SGLT2-I users, in non-T2DM vs non-SGLT2-I users, and SGLT2-I users vs non-SGLT2-I users. Results: At baseline, and at one year and 5 years of follow-up, the non-T2DM vs SGLT2-I users, non-T2DM vs non-SGLT2-I users, and SGLT2-I users vs non-SGLT2-I users had the lowest values of IL-1, IL-6, and TNF-α (p < 0.05). At one year of follow-up, SGLT2-I users vs non-T2DM and non-SGLT2-I users vs non-T2DM users had a higher rate of all deaths, cardiac deaths, re-myocardial infarction, repeat revascularization, and stroke, and of the composite endpoint (p < 0.05). In a multivariate Cox regression analysis, the composite endpoint was predicted by IL-1 [2.068 (1.367-3.129)], TNF-α [1.989 (1.081-2.998)], and SGLT2-I [0.504 (0.078-0.861)]. Conclusion: In T2DM patients, the SGLT2-I significantly reduced the inflammatory burden and ameliorated clinical outcomes at 5 years of follow-up post-CABG via MiECC.

Keywords: coronary artery bypass grafting; minimally invasive extracorporeal circulation; multi-vessel coronary stenosis; over-inflammation; sodium-glucose transporter 2 inhibitors; type 2 diabetes mellitus, coronary heart disease.