Abstract 15701: Relationship Between Cardiac Biomarkers and Major Adverse Cardiovascular Events in DECLARE-TIMI 58

Abstract

Introduction: Biomarkers of hemodynamic stress and myocardial injury are associated with the risk of CV death & heart failure in patients with atherosclerotic vascular disease (ASCVD). Here we explore the association between cardiac biomarkers and ASCVD outcomes in patients with type 2 diabetes (T2DM). Methods: This was a nested biomarker study in DECLARETIMI 58, a randomized, blinded, placebo-controlled trial of dapagliflozin in T2DM and either multiple risk factors (MRF, ~60%) or established ASCVD (~40%). The relationship between baseline NT-proBNP and hsTnT levels (TIMI Biomarker Laboratory, n=14,565) and the composite of myocardial infarction, ischemic stroke, and CV death (MACE), was modeled within the placebo arm using Cox models adjusted for age, sex, race, smoking, baseline eGFR, BMI, T2DM duration, insulin use, history of CAD, MI, ischemic stroke, PAD, HF, dyslipidemia & hypertension. Interaction testing was applied to assess the effect of dapagliflozin according to baseline biomarker value. Results: NT-proBNP and hsTnT were significantly associated with MACE (Adjusted hazard ratio (aHR) per 1-SD in log-transformed biomarker, NT-proBNP: aHR 1.62; hsTnT aHR 1.59). The magnitude of the relationship was similar in patients with ASCVD (NT-proBNP aHR 1.60; hsTnT aHR 1.62) and MRF (NT-proBNP aHR 1.62; hsTnT: aHR 1.51) [Fig A] . Moreover, both biomarkers remained independently associated with MACE when combined in the multivariable model (NT-proBNP aHR 1.46, hsTnT aHR 1.39). The risk of MACE by baseline biomarker level and stratified by treatment arm is shown in Fig B. Conclusions: In patients with T2DM both with and without ASCVD, higher baseline NT-proBNP or hsTnT levels identified patients at increased risk of MACE. The difference in MACE rates between dapagliflozin and placebo tended to be more pronounced in ASCVD patients with higher baseline or NT-proBNP or hsTnT levels.