Heart Failure Risk Stratification and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes Mellitus

Abstract

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing heart failure (HF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce the risk of hospitalization for HF (HHF) in patients with T2DM. We aimed to develop and validate a practical clinical risk score for HHF in patients with T2DM and assess whether this score can identify high-risk patients with T2DM who have the greatest reduction in risk for HHF with an SGLT2 inhibitor. We developed a clinical risk score for HHF in 8,212 patients with T2DM in the placebo arm of SAVOR-TIMI 53. Candidate variables were assessed using multivariable Cox regression, and independent clinical risk indicators achieving statistical significance of p<0.001 were included in the risk score. We externally validated the score in 8,578 patients with T2DM in the placebo arm of DECLARE-TIMI 58. The relative and absolute risk reductions in HHF with the SGLT2 inhibitor dapagliflozin were assessed by baseline HHF risk. Five clinical variables were independent risk predictors of HHF: prior HF, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate (eGFR), and urine albumin-to-creatinine ratio (UACR). A simple integer-based score (0–7 points) using these predictors identified a >20-fold gradient of HHF risk (p-trend <0.001) in both the derivation and validation cohorts, with c-indices of 0.81 and 0.78, respectively. Whereas relative risk reductions with dapagliflozin were similar for patients across the risk scores (25–34%), absolute risk reductions were greater in those at higher baseline risk (χ 2 3.24; one-sided p-trend=0.04), with high-risk (2 points) and very high-risk patients (≥3 points) having 1.5% and 2.7% absolute reductions in Kaplan-Meier estimates of HHF risk at 4 years. Risk stratification using a novel clinical risk score for HHF in patients with T2DM identifies patients at higher risk for HHF who derive greater absolute benefit from SGLT2 inhibition. URL: https://www.clinicaltrials.gov . Unique identifiers: and .