Abstract 12923: Development of a Novel Biomarker-based Risk Score for Heart Failure in Patients With Diabetes

Abstract

Introduction: Heart failure (HF) is a prognostically important complication of T2DM, the risk of which can be reduced by SGLT2 inhibitors. Clinical factors and circulating biomarkers of myocardial injury and hemodynamic stress predict risk of hosp for HF (HHF) in pts with T2DM. Aim: We aimed to develop and validate a biomarker-based risk score for HHF in pts with T2DM and to assess whether this score can identify high-risk pts with T2DM who have the greatest reduction in HHF risk with SGLT2 inhibition. Methods: Blood samples were prospectively collected from pts enrolled in SAVOR-TIMI 53 and DECLARE-TIMI 58 at randomization; high-sensitivity troponin T (hsTnT) and N-terminal B-type natriuretic peptide (NT-proBNP) were measured. We derived a risk score in 6106 pts with T2DM in the placebo arm of SAVOR-TIMI 53. Candidate variables (n=27) were assessed using Cox regression. The strongest indicators of HHF risk (based on Wald χ;2 values) were selected for inclusion and assigned integer weights. We externally validated the score in 7251 T2DM pts in the placebo arm of DECLARE-TIMI 58. Hazard ratios (HR) and absolute risk reductions (ARR) in HHF with the SGLT2 inhibitor dapagliflozin were assessed by baseline risk group. Results: The strongest independent indicators of HHF risk were NT-proBNP and hsTnT concentrations, and prior HF (each p<0.001). A risk score using these 3 variables identified a strong gradient of HHF risk (p-trend <0.001) in both the derivation and validation cohorts, with c-indices of 0.87 and 0.84, respectively. HRs with dapagliflozin were similar across risk groups (p-int = 0.64); however, ARRs were greater in those at higher baseline risk (p-trend <0.001), with high- (10-13 points) and very high-risk (14+ points) pts having 3.2% and 4.4% ARRs in KM estimates of HHF at 4 yrs, respectively ( Fig ). Conclusions: A novel biomarker-based risk score for HHF in pts with T2DM identifies pts at higher risk of HHF who derive greater absolute benefit from SGLT2 inhibitors.