Abstract 14915: Efficacy of Canagliflozin on Heart Failure Hospitalization Across Diabetes-Specific Risk Scores

Introduction:Canagliflozin (CAN) vs. placebo (PBO) reduced the risk of hospitalization for heart failure (HHF) in type 2 diabetes. Whether this benefit is uniform across diabetes-specific HF risk scores (WATCH-DM and TRS-HFDM) is not known.Methods:Using data from the pooled CANVAS and CANVAS-R trials, we stratified participants without prevalent HF by the integer WATCH-DM score derived quintiles (low [≤14] = quintiles 1-2, intermediate [15-19] = quintiles 3-4, high [≥20] = quintile 5) and by the TRS-HFDMscore (low [0-1], intermediate [2], high [3-6]). Discrimination and calibration were assessed by Harrell’s C-index and Hosmer-Lemeshow test, respectively. Cox regression models evaluated the effect of CAN on risk of HHF across risk score categories.Results:Among participants without prevalent HF (n = 8,691), CAN vs. PBO reduced the risk of HHF (HR 0.80, 95% CI 0.62-1.03). The WATCH-DM score demonstrated a C-index of 0.70 (95% CI, 0.66-0.73) and no evidence of miscalibration (χ2< 20). CAN consistently reduced risk of HHF across WATCH-DM strata (P-intxn = 0.55) with the greatest absolute risk reduction and lowest NNT observed in the highest vs. lowest risk cohort (ARR 4.6% vs. 0.3% and NNT 22 vs. 333) (Fig. A). Comparatively, the TRS-HFDMdemonstrated a C-index of 0.67 (95% CI, 0.63-0.71) and no evidence of miscalibration (χ2< 20). Similar to WATCH-DM, patients in the highest TRS-HFDMrisk group derived the greatest absolute risk reduction and lowest NNT (ARR 3.1% vs. -0.3%% and NNT 32 vs. -333) with no differences across strata (P-intxn = 0.17) (Fig. B).Conclusions:Both the WATCH-DM and TRS-HFDMcan accurately stratify HHF risk in patients with type 2 diabetes and free of HF. Greater absolute risk reductions with CAN vs PBO were observed with higher risk scores.