SGLT2-inhibitors effects on the coronary fibrous cap thickness and MACEs in diabetic patients with inducible myocardial ischemia and multi vessels non-obstructive coronary artery stenosis

Abstract

Background Sodium–glucose transporter 2 inhibitors (SGLT2-I) could modulate atherosclerotic plaque progression, via down-regulation of inflammatory burden, and lead to reduction of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) patients with ischemic heart disease (IHD). T2DM patients with multivessel non-obstructive coronary stenosis (Mv-NOCS) have over-inflammation and over-lipids’ plaque accumulation. This could reduce fibrous cap thickness (FCT), favoring plaque rupture and MACEs. Despite this, there is not conclusive data about the effects of SGLT2-I on atherosclerotic plaque phenotype and MACEs in Mv-NOCS patients with T2DM. Thus, in the current study, we evaluated SGLT2-I effects on Mv-NOCS patients with T2DM in terms of FCT increase, reduction of systemic and coronary plaque inflammation, and MACEs at 1 year of follow-up. Methods In a multi-center study, we evaluated 369 T2DM patients with Mv-NOCS divided in 258 (69.9%) patients that did not receive the SGLT2-I therapy (Non-SGLT2-I users), and 111 (30.1%) patients that were treated with SGLT2-I therapy (SGLT2-I users) after percutaneous coronary intervention (PCI) and optical coherence tomography (OCT) evaluation. As the primary study endpoint, we evaluated the effects of SGLT2-I on FCT changes at 1 year of follow-up. As secondary endpoints, we evaluated at baseline and at 12 months follow-up the inflammatory systemic and plaque burden and rate of MACEs, and predictors of MACE through multivariable analysis. Results At 6 and 12 months of follow-up, SGLT2-I users vs. Non-SGLT2-I users showed lower body mass index (BMI), glycemia, glycated hemoglobin, B-type natriuretic peptide, and inflammatory cells/molecules values (p < 0.05). SGLT2-I users vs. Non-SGLT2-I users, as evaluated by OCT, evidenced the highest values of minimum FCT, and lowest values of lipid arc degree and macrophage grade (p < 0.05). At the follow-up end, SGLT2-I users vs. Non-SGLT2-I users had a lower rate of MACEs [n 12 (10.8%) vs. n 57 (22.1%); p < 0.05]. Finally, Hb1Ac values (1.930, [CI 95%: 1.149–2.176]), macrophage grade (1.188, [CI 95%: 1.073–1.315]), and SGLT2-I therapy (0.342, [CI 95%: 0.180–0.651]) were independent predictors of MACEs at 1 year of follow-up. Conclusions SGLT2-I therapy may reduce about 65% the risk to have MACEs at 1 year of follow-up, via ameliorative effects on glucose homeostasis, and by the reduction of systemic inflammatory burden, and local effects on the atherosclerotic plaque inflammation, lipids’ deposit, and FCT in Mv-NOCS patients with T2DM.

Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Intima-Media Thickness: Systematic Review and Meta-Analysis

“…Eighteen studies examined the effects of GLP-1 RA [ 11 – 13 , 16 – 31 ], and eleven examined the effects of SGLT2i on IMT [ 32 – 42 ]. Studies that did not provide IMT results [ 43 – 49 ], duplicate data [ 50 – 56 ], combination therapies without apparent GLP-1 RA effects [ 57 ], or assessed IMT of arteries other than the carotid artery were excluded [ 58 – 60 ]. The study selection process is shown in Figure 1 .…”

Co-release of cytokines after Drug-Eluting Stent Implantation in Acute Myocardial Infarction Patients with PCI

“…The principle cytokines are mainly IL8 and TNFα with Hs-CRP (Hypersensitive C-Reactive Protein) for AMI 10 11 , TNFα, Hs-CRP, IL6 with STEMI patients 12 , IL-1ß for coronary endothelial dysfunction in CAD (Coronary Artery Disease) patients 13 , IL6, IL8, and TNFα for patients with severe stenosis in a saphenous vein 14 , TNFα for restenosis patients after coronary angiography 15 , IL-1ß, IL6 and TNFα for AMI patients with signi cant stenosis of the ramus interventricularis anterior 16 . T2DM Mv-NOCS patients with SGLT2 inhibitor users showed reduced BMI, and in ammation than non-users with lower levels of NLRP3 in ammasome formation and IL-1ß 17 . Adiponectin that is exclusively secreted from adipose tissue and in ammatory cytokines including TNFα, PAI-1 (Plasminogen Activator Inhibitor type 1), IL-6, leptin, and resistin favorably modulate the endothelial in ammatory responses to vascular injury 18 and linked to restenosis and Acute Coronary symptoms after PCI 19 .…”

Exploring new insights in coronary lesion assessment and treatment in patients with diabetes mellitus: the impact of optical coherence tomography

“…Indeed, more evidence is emerging that SGLT2 inhibitors may have ameliorative effects on glucose homeostasis and advantageous pleiotropic glucose-independent effects on coronary plaque development. A recent study showed that DM patients with multivessel non-obstructive CAD treated with SGLT2 inhibitors had significantly higher values of OCT-detected fibrous cap thickness, fewer lipid deposits (measured as the lipid arc) and less macrophage infiltration than DM patients not treated with SGLT2 inhibitors [ 78 ]. In addition, a lower incidence of major adverse cardiovascular events was observed in this patient group [ 78 ].…”

“…A recent study showed that DM patients with multivessel non-obstructive CAD treated with SGLT2 inhibitors had significantly higher values of OCT-detected fibrous cap thickness, fewer lipid deposits (measured as the lipid arc) and less macrophage infiltration than DM patients not treated with SGLT2 inhibitors [ 78 ]. In addition, a lower incidence of major adverse cardiovascular events was observed in this patient group [ 78 ]. Furthermore, in other studies with DM patients treated by PCI after MI, SGLT2 inhibitors were associated with a reduction in both safety outcomes and in-stent restenosis-related events [ 79 , 80 ].…”