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

doi:10.3389/fphar.2021.777083

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.

Highlights

Invasive extracorporeal circulation (MiECC) reduced inflammatory burden, leading to best clinical outcomes in patients treated with coronary artery bypass grafting (CABG)
At one year of follow-up, sodium-glucose transporter 2 inhibitor (SGLT2-I) users vs non-type 2 diabetes mellitus (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
Little is known about the effects on the glucose homeostasis, overinflammation, and the clinical outcomes exerted by SGLT2-I in T2DM treated with CABG via Minimally invasive extracorporeal circulation (MiECC) (Verma et al, 2018; Sardu et al, 2021)

Summary

Introduction

Invasive extracorporeal circulation (MiECC) reduced inflammatory burden, leading to best clinical outcomes in patients treated with coronary artery bypass grafting (CABG). This over-inflammatory response could lead to a worse prognosis in CABG-treated patients, and in those with T2DM (Wan et al, 1997; Neumann et al, 2018) In this context, the minimally invasive extracorporeal circulation circuit (MiECC) could reduce perioperative inflammation and ameliorate post-CABG’s clinical outcomes (Anastasiadis et al, 2016). The altered glucose homeostasis and insulin resistance could cause over-inflammation, linked to an increased expression of sodium-glucose transporter 2 receptors, and to worse prognosis post-CABG (Sardu et al, 2019b; Sardu et al, 2021) In this context, in T2DM patients treated with CABG, the sodium-glucose transporter 2 inhibitor (SGLT2-I) “empagliflozin” lead to a profound reduction in cardiovascular and all-cause mortality, hospitalization for heart failure, and incident or worsening nephropathy (Verma et al, 2018). In these cohorts, we investigated the clinical outcomes in terms of all death, cardiac death, myocardial infarction, stroke, repeat revascularization, and composite endpoint at 1 and 5 years of follow-up after CABG

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