The Fate of PCI in Diabetics

Diabetes mellitus is a major cardiovascular risk factor, present in approximately 20%-30% of patients who require coronary revascularization. The vascular biology of diabetes is characterized by systemic endothelial dysfunction, platelet abnormalities that result in a prothrombotic milieu, increased systemic inflammation, and accelerated atherosclerosis. Diabetics have smaller caliber coronary vessels and more diffuse and extensive coronary disease. The inception of drug-eluting stents (DES) has decreased restenosis and repeat revascularization in diabetics undergoing percutaneous coronary interventions (PCI). However, among diabetic patients with multivessel disease, coronary artery bypass grafting (CABG) is associated with  lower mortality and major adverse cardiovascular and cerebral events compared to PCI.

Gaps in knowledge

There have been multiple advances in PCI  for diabetics including new generation stents with thinner stent struts, and polymers with higher biocompatibility. However, restenosis and repeat revascularization rates remain higher in diabetics, and it is not clear whether or not biodegradable polymers are associated with better outcomes. There is a need for the development of agents that interrupt signaling pathways that predispose to restenosis in diabetes.

Even though low ejection fraction, multivessel disease, and diabetes is a classic indication for CABG, there is a paucity of randomized clinical trials or sufficiently powered subgroup analyses examining revascularization outcomes in diabetic patients with systolic left ventricular dysfunction. In trials comparing PCI versus CABG in diabetics, patients with low ejection fraction are significantly underrepresented.

Possible solutions and future directions

New technologies that may have an impact in diabetic patients include new stent platforms, including polymer-free stents, reengineered bioresorbable vascular scaffolds, and drug-filled stents. Advances in this area could allow improved vessel healing and endothelial coverage, similar to bare metal stents, with the advantage of preventing restenosis. Intravascular lithotripsy for calcific vessels is a promising technology for PCI optimization in diabetics with diffusely diseased and calcified vessels.

Systematic physiologic assessment of coronary lesions in diabetics with estimation of a “functional SYNTAX score,” instead of a purely anatomic score, allows reclassification of diabetics with multivessel disease into a lower SYNTAX category (≤32). These patients may be treated with optimized PCI strategies. Non-invasive functional assessment of coronary lesions is now possible with FFR_CT, which may help guide coronary interventions and identify diabetic patients who would derive similar benefits with PCI compared to CABG. However, this imaging modality has not been widely adopted in clinical practice yet.

Hybrid revascularization strategies using a left internal mammary graft for LAD lesions and DES for non-LAD stenoses is an appealing strategy that deserves further study. Unfortunately, hybrid revascularization has not been adopted in clinical practice and the NIH-sponsored Hybrid Trial has been stopped for poor enrollment. In addition, revascularization strategies in general need to be better studied in diabetic patients with low systolic left ventricular function.

Regardless of the revascularization strategy selected, diabetics remain at high risk   for recurrent events. Wide implementation of multidisciplinary disease management programs to improve therapeutic goals in diabetics is necessary. These goals include use of potent antiplatelet agents, tighter glycemic control, aggressive lipid lowering with high-dose statin therapy and/or use of PSK9 inhibitors. Broader adoption of sodium-glucose contransporter-2 inhibitors (SGLT2i) is warranted in diabetic patients with established atheroschlerotic disease, in light of clinical trial data demonstrating reduced risk of cardiovascular events.