Abstract 14799: Cardiovascular Risk Stratification and Efficacy of Dapagliflozin on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus in the DECLARE-TIMI 58 Trial

Introduction: In DECLARE-TIMI 58, the SGLT-2 inhibitor, dapagliflozin reduced the risk of the composite of cardiovascular death (CVD) or hospitalization for heart failure (HHF), and renal-specific outcomes in a broad range of patients with type 2 diabetes mellitus (T2DM). The TIMI Risk Score for Secondary Prevention (TRS 2°P) is a clinical risk score developed in patients with atherosclerotic cardiovascular disease (ASCVD) that provides risk stratification. Hypothesis: We hypothesized that the TRS 2°P would provide risk stratification in this population and that dapagliflozin would provide cardiovascular protection regardless of risk. Methods: DECLARE-TIMI 58 included patients with T2DM and either multiple risk factors or established ASCVD. Patients were stratified into 3 risk categories based on the 10-point TRS 2°P (see Figure , low: 1 or 2 points, intermediate: 3 points, or high: ≥4 points). Outcomes were major adverse cardiovascular events (MACE) (CVD, myocardial infarction, or ischemic stroke), CVD/HHF, components for MACE, and renal-specific composite outcomes. Results: Low, intermediate, or high risk, comprised respectively 49.8%, 31.2%, and 19.0% of the total of 17159 patients. In the placebo arm, increasing risk category was associated with a higher risk of all the outcomes of interest across risk categories (P-trend<0.001 for each) ( Figure ). The C-statistics were 0.67 for MACE and 0.72 for CVD/HHF in the placebo arm. Relative risk reductions in CVD/HHF and renal-specific composite outcomes with dapagliflozin were consistent for patients across the spectrum of TRS 2°P (P>0.05 for each interaction). Conclusions: Cardiovascular risk stratification using TRS 2°P identifies high-risk patients with T2DM for MACE, CVD/HHF, individual components for MACE, and renal-specific outcomes. Reductions in CVD/HHF and renal-specific outcomes with dapagliflozin versus placebo were consistent across the range of TRS 2°P.