Abstract TP134: Association of Diabetes, Glycemic Control, and Macroalbuminuria with Ischemic and Bleeding Risk During Antithrombotic Therapy

Background: Diabetes mellitus induces a prothrombotic state through mechanisms including platelet activation, leading to reduced responsiveness to antithrombotic therapy. However, the clinical consequences of diabetes, glycemic control, and diabetic nephropathy on the risk of ischemic and bleeding events under antithrombotic therapy have not been fully investigated. Methods: This was a prospective, multicenter observational study, enrolling patients receiving oral antiplatelets or anticoagulants. Baseline brain MRI was performed to assess small vessel disease (SVD): white matter hyperintensity, cerebral microbleed, lacune, enlarged perivascular space, with central reading. The SVD burden was defined as SVD score >2 (range, 0–4). Cox regression models were used to evaluate the associations of diabetes, hemoglobin A1c (HbA1c) categories (<6, 6–7, ≥7 %), and diabetes with macroalbuminuria (≥300 mg/gCr) with the risks of ischemic events, ischemic stroke, major bleeding, intracranial hemorrhage, and mortality. The covariate included conventional vascular risk factors and the SVD burden. Results: Of the analyzed 5,249 patients (median age 73 [IQR 66–79] years), diabetes was present in 1,460 (28%), and the median HbA1c level was 5.9 (IQR 5.6–6.4) %. The SVD burden was observed in 1,400 (27%). During a median of 2 (IQR1.8–2.0) years, 278 ischemic events, 197 ischemic strokes, 93 major bleedings, 55 intracranial hemorrhages, and 217 deaths were observed. Diabetes was associated with an increased risk of ischemic events and ischemic stroke (adjusted hazard ratio [aHR]: 1.62, 95%CI: 1.25–2.1; aHR: 1.41 [1.03–1.94], respectively). A higher HbA1c level (≥7.0%) was also associated with an increased risk of ischemic events and ischemic stroke (aHR: 1.76 [1.24–2.5]; aHR: 1.55, [1.02–2.38], respectively). Diabetes and HbA1c categories were not associated with major bleeding, intracranial hemorrhage, or mortality. Macroalbuminuria was observed in 230 of 3,114 (7.4%). Patients with diabetes and macroalbuminuria had an increased risk of major bleeding (aHR: 2.67 [1.11–6.34]), compared to those without diabetes and macroalbuminuria. Conclusions: Diabetes and poor glycemic control remain independent risk factors for ischemic events in patients with antithrombotic therapy. In addition, diabetes with macroalbuminuria was associated with a significantly higher risk of major bleeding, highlighting implications for clinical decision making in long-term antithrombotic therapy.