Optimal revascularization in diabetes after the FREEDOM trial: Were the controversies finally settled?

The prevalence of diabetes mellitus (DM) is growing worldwide. Prothrombotic and proinflammatory states, in adjunct to endothelial dysfunction and metabolic disorders, such as hyperglycemia, dyslipidemia, obesity, insulin resistance, and oxidative stress, are key features of the accelerated atherosclerotic progression observed in patients with DM. Moreover, drug-eluting stents (DES) thrombosis rate was higher in DM than in non-DM patients and DM itself was identified as an independent predictor of stent thrombosis, particularly due to the impaired response to dual antiplatelet therapy. The accumulating data even before the FREEDOM trial provided strong evidence that in patients with DM and complex coronary artery disease, coronary artery bypass grafting (CABG) was superior to percutaneous coronary intervention (PCI) which was based on the first-generation DES. The FREEDOM trial enrolled 1900 patients with DM and multivessel coronary artery disease treated with CABG surgery or PCI with the first-generation DES. The patients were followed for a median 3.8 years; CABG was superior to PCI as it significantly reduced rates of death and myocardial infarction (MI), with a higher rate of stroke. The benefit of CABG was driven by differences in rates of both MI (p < 0.001) and death from any cause (p = 0.049). Following the FREEDOM results, patients with DM ought to be informed before coronary angiography about the potential survival benefit from CABG for the treatment of a complex disease. However, it should be noticed that the second generation DES were associated with better outcomes compared to the first-generation DES. New stent designs are continually being developed, with the aim of further improving the clinical efficacy and the safety profile of these devices. Therefore, although the results of the FREEDOM trial clearly demonstrated that CABG was superior to PCI in DM, a comparative analysis of the new incoming stents warrants further investigation.