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

Eline H Ploumen, Tineke H Pinxterhuis, Paolo Zocca, Ariel Roguin, Rutger L Anthonio, Carl E Schotborgh, Edouard Benit, Adel Aminian, Peter W Danse, Carine J M Doggen, Clemens von Birgelen, Marlies M Kok, Eline H Ploumen, Tineke H Pinxterhuis, Paolo Zocca, Ariel Roguin, Rutger L Anthonio, Carl E Schotborgh, Edouard Benit, Adel Aminian, Peter W Danse, Carine J M Doggen, Clemens von Birgelen, Marlies M Kok

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.

Keywords: Coronary artery disease; Diabetes mellitus; Drug-eluting stents; Percutaneous coronary intervention; Prediabetes; Randomized clinical trial.

Conflict of interest statement

CvB reports that the research department of Thoraxcentrum Twente has received institutional research grants provided by Abbott Vascular, Biotronik, Boston Scientific, and Medtronic. RLA reports a teaching grant from Biotronic, a lincense from Sanovi, a speaking fee from Abiomed and support from Amgen for attending a meeting, all outside the submitted work. All other authors declared that they have no potential conflict of interest.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Study flow diagram. Study flow diagram showing the number of patients included from each randomized clinical trial
Fig. 2
Fig. 2
Kaplan–Meier event curves for target vessel failure and its individual components at 3-year follow-up. Kaplan–Meier event curves for target vessel failure and its individual components up to 3-year follow-up showing higher rates of the main endpoint in patients with prediabetes and diabetes as compared to patients with normoglycemia
Fig. 3
Fig. 3
Kaplan–Meier event curves for major bleeding and stent thrombosis at 3-year follow-up. Kaplan–Meier event curves for major bleeding and stent thrombosis up to 3-year follow-up showing higher rates of major bleeding in patients with prediabetes and diabetes, and higher rates of definite-or-probable stent thrombosis in patients with diabetes as compared to patients with normoglycemia

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Source: PubMed

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