Glycaemic Control in Patients Undergoing Percutaneous Coronary Intervention: What Is the Role for the Novel Antidiabetic Agents? A Comprehensive Review of Basic Science and Clinical Data

Abstract

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and revascularization through percutaneous coronary interventions (PCI) significantly improves survival. In this setting, poor glycaemic control, regardless of diabetes, has been associated with increased incidence of peri-procedural and long-term complications and worse prognosis. Novel antidiabetic agents have represented a paradigm shift in managing patients with diabetes and cardiovascular diseases. However, limited data are reported so far in patients undergoing coronary stenting. This review intends to provide an overview of the biological mechanisms underlying hyperglycaemia-induced vascular damage and the contrasting actions of new antidiabetic drugs. We summarize existing evidence on the effects of these drugs in the setting of PCI, addressing pre-clinical and clinical studies and drug-drug interactions with antiplatelet agents, thus highlighting new opportunities for optimal long-term management of these patients.

Keywords: anti-diabetic agents; coronary artery disease; coronary stenting; diabetes mellitus; glycaemic control; glycaemic variability; hyperglycaemia; percutaneous coronary intervention.

Figure 1

Pathophysiological mechanisms of hyperglycaemia-induced vascular damage. AGE, advanced glycation end products; PKC, protein kinase C; e-NOS, endothelial nitric oxide synthase; VEGF, vascular endothelial grow factor; ICAM-1, intercellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1; PUMA, p53 upregulated modulator of apoptosis; PTEN, phosphatase and TENsin homolog deleted on chromosome 10; TIGAR, TP53-Induced Glycolysis and Apoptosis Regulator; NO, nitric oxide; TxA2, Thromboxane A2; TF, tissue factor; GP, glycoprotein; MAPK, mitogen-activated protein kinase; BMK, big MAPK; PI3K, Phosphoinositide 3-kinases; NF-kB, nuclear factor kappa B; IRS-1, insulin receptor substrate 1; KLF-4, Kruppel Like Factor 4; ERK, extracellular signal-regulated kinase; BCL, B-cell lymphoma; Bft, Bacteroides fragilis toxin; MAC, membrane attack complex; LFA-1, lymphocyte function-associated antigen 1; MCP-1, monocyte chemoattractant protein-1; IL, interleukin; TNF, tumour necrosis factor.

Figure 2

Peri-procedural and long-term stent-related complications favored by an abnormal glycaemic status.

Figure 3

Potential mechanisms of benefit of novel antidiabetic agents in the setting of PCI. PCI, percutaneous coronary intervention; GLP-1 RAs, glucagon-like peptide 1 receptor agonist; DPP4i, dipeptidyl peptidase-4 inhibitors; SGLT-2i, sodium-glucose cotransporter-2 inhibitors; NO, nitric oxide; ROS, reactive oxygen species; EPCs, endothelial progenitor cells; MMPs, matrix metalloprotease; VSMCs, vascular smooth muscular cell.