Impact of prediabetes and diabetes on 3-year outcome of patients treated with new-generation drug-eluting stents in two large-scale randomized clinical trials

Abstract

Background Diabetes is associated with adverse outcomes after percutaneous coronary intervention with drug-eluting stents (DES), but for prediabetes this association has not been definitely established. Furthermore, in patients with prediabetes treated with contemporary stents, bleeding data are lacking. We assessed 3-year ischemic and bleeding outcomes following treatment with new-generation DES in patients with prediabetes and diabetes as compared to normoglycemia. Methods For this post-hoc analysis, we pooled patient-level data of the BIO-RESORT and BIONYX stent trials which both stratified for diabetes at randomization. Both trials were multicenter studies performed in tertiary cardiac centers. Study participants were patients of whom glycemic state was known based on hemoglobin A1c, fasting plasma glucose, or medically treated diabetes. Three-year follow-up was available in 4212/4330 (97.3 %) patients. The main endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization. Results Baseline cardiovascular risk profiles were progressively abnormal in patients with normoglycemia, prediabetes, and diabetes. The main endpoint occurred in 54/489 patients with prediabetes (11.2 %) and 197/1488 with diabetes (13.7 %), as compared to 142/2,353 with normoglycemia (6.1 %) (HR: 1.89, 95 %-CI 1.38–2.58, p < 0.001, and HR: 2.30, 95 %-CI 1.85–2.86, p < 0.001, respectively). In patients with prediabetes, cardiac death and target vessel revascularization rates were significantly higher (HR: 2.81, 95 %-CI 1.49–5.30, p = 0.001, and HR: 1.92, 95 %-CI 1.29–2.87, p = 0.001), and in patients with diabetes all individual components of the main endpoint were significantly higher than in patients with normoglycemia (all p ≤ 0.001). Results were consistent after adjustment for confounders. Major bleeding rates were significantly higher in patients with prediabetes and diabetes, as compared to normoglycemia (3.9 % and 4.1 % vs. 2.3 %; HR:1.73, 95 %-CI 1.03–2.92, p = 0.040, and HR:1.78, 95 %-CI 1.23–2.57, p = 0.002). However, after adjustment for confounders, differences were no longer significant. Conclusions Not only patients with diabetes but also patients with prediabetes represent a high-risk population. After treatment with new-generation DES, both patient groups had higher risks of ischemic and bleeding events. Differences in major bleeding were mainly attributable to dissimilarities in baseline characteristics. Routine assessment of glycemic state may help to identify patients with prediabetes for intensified management of cardiovascular risk factors. Trial registration: BIO-RESORT ClinicalTrials.gov: NCT01674803, registered 29-08-2012; BIONYX ClinicalTrials.gov: NCT02508714, registered 27-7-2015.

Angiographic complete revascularization versus incomplete revascularization in patients with diabetes mellitus

“…It has been demonstrated that CAD in the DM population was more likely to be diffuse disease and multivessel disease [ 24 ], and was associated with more significant plaque burden and lipid-rich plaque, prone to rupture [ 2 ], which lead to a procedural complexity in reperfusion therapy. DM is also associated with adverse stent-related outcomes after PCI, increasing the risk of stent restenosis or thrombotic obstructions [ 4 – 7 ]. A pooled analysis of BIO-RESOR and BIONYX trials demonstrated that patients with DM had higher risks of target lesion failure than patients without DM after PCI [ 7 ].…”

“…DM is also associated with adverse stent-related outcomes after PCI, increasing the risk of stent restenosis or thrombotic obstructions [ 4 – 7 ]. A pooled analysis of BIO-RESOR and BIONYX trials demonstrated that patients with DM had higher risks of target lesion failure than patients without DM after PCI [ 7 ]. Furthermore, a recent study by Kim et al reported a greater plaque progression in the DM population using serial coronary computed tomographic angiography data [ 25 ].…”

“…DM is also related to vulnerable plaque features, such as high plaque burden or lipid-rich plaque [ 2 ]. Patients with DM who underwent percutaneous coronary intervention (PCI) tend to be associated with a worse prognosis than those without DM due to an increased risk of stent restenosis and thrombotic obstruction [ 4 – 7 ]. All of these lead to more challenging PCI in the DM population.…”

Hemoglobin A1C as a prognostic factor and the pre-diabetic paradox in patients admitted to a tertiary care medical center intensive cardiac care unit

“…This study has shown that after treatment with new-generation drug-eluting stents, both patient groups had higher risks of ischemic and bleeding events compared with non-DM patients. Differences in major bleeding were mainly attributable to dissimilarities in baseline characteristics [ 19 ] .…”

One-year outcomes of polymer-free amphilimus-eluting stents versus durable polymer zotarolimus-eluting stents in patients with diabetes mellitus: a meta-analysis

“…This analysis was based on patients with diabetes mellitus, however, not only patients with diabetes mellitus but, patients with pre-diabetes were at a higher risk for ischemic events following newer generation stents implantation. This was shown in a post-hoc analysis whereby data from the BIO-RESORT and BIONYX stent trials were pooled for study analysis [ 21 ]. In addition, when second generation DES were compared with first generation DES, stent related adverse events were significantly lower with the second generation DES, however, it was observed that the use of dual antiplatelet therapy beyond one year did not reduce late stent thrombosis among patients who were revascularized with second generation DES, but late stent thrombosis was reduced in patients who were implanted with first generation DES [ 22 ].…”