Is Diabetes the Achilles' Heel of Limus-Eluting Stents?

Patients with diabetes have a 2- to 4-fold increase in the risk of coronary artery disease.1 They have accelerated and more diffuse coronary artery disease2 with increased need for revascularization therapy.3 In addition, patients with diabetes have worse outcomes after surgical or catheter-based revascularization procedures.4 Diabetes promotes endothelial dysfunction and platelet deposition, which enhance the propensity to thrombosis.5 Hyperglycemia is associated with overexpression of several growth factors, and advanced glycosylation promotes inflammatory cell recruitment and smooth muscle cell proliferation.5 Indeed, an excess risk of coronary thrombosis and restenosis has characterized the outcomes of diabetic patients treated with balloon angioplasty or bare-metal stents (BMS).2,6 Although drug-eluting stents (DES) provide better chances than BMS for diabetic patients who need coronary revascularization,7 diabetes remains an important risk factor for coronary events even in the DES era. Moreover, findings about an attenuation of the mammalian target of rapamycin (mTOR) signaling pathway in patients with type 2 diabetes8 have generated concerns about a possible specific limitation of limus-eluting stents in diabetic patients that has not been fully dispelled by existing clinical evidence.Articles see p 886 and p 893Diabetic patients are in bad need of the best available DES, and 2 studies published in the current issue of Circulation considerably serve our efforts in defining optimal DES strategy in these patients. In the study of Stone et al,9 the investigators pooled together the individual patient data from 4 randomized trials—the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) II, SPIRIT III, SPIRIT IV trials, and the Second-Generation Everolimus-Eluting and Paclitaxel-Eluting Stents in Real-Life Practice (COMPARE) trial—that compared everolimus-eluting stents (EES) with paclitaxel-eluting stents (PES) in patients …