SO019EFFECTS OF EMPAGLIFLOZIN ON CARDIOVASCULAR OUTCOMES ACROSS KDIGO RISK CATEGORIES: RESULTS FROM THE EMPA-REG OUTCOME® TRIAL

Abstract

INTRODUCTION AND AIMS: Chronic kidney disease (CKD) is a strong risk factor for cardiovascular (CV) disease, causing substantial morbidity and mortality in this population. In the EMPA‐REG OUTCOME® trial, empagliflozin (EMPA) given in addition to standard of care significantly reduced 3‐point major adverse CV events (3‐point MACE: composite of CV death, non‐fatal myocardial infarction, or non‐fatal stroke), CV death, and hospitalization for heart failure (HHF), versus placebo (PBO) in people with type 2 diabetes mellitus (T2DM) and established CV disease. The Kidney Disease: Improving Global Outcomes (KDIGO) CKD guidelines introduced a risk category framework based on eGFR and urine albumin‐creatinine ratio (UACR) values. We investigated CV outcomes in subgroups of participants at different levels of risk in the EMPA‐REG OUTCOME® trial. METHODS: Participants were randomized to receive EMPA 10 mg, EMPA 25 mg, or PBO. The outcomes of 3‐point MACE, CV death, and HHF were analyzed in subgroups by baseline KDIGO risk category, defined as low risk (eGFR ≥60 ml/min/ 1.73m2 and UACR <30 mg/g), moderately increased risk (eGFR 45‐59 ml/min/1.73m2 and UACR <30 mg/g, or eGFR ≥60 ml/min/1.73m2 and UACR 30‐300 mg/g), high risk (eGFR 30‐44 ml/min/1.73m2 and UACR <30 mg/g, eGFR 45‐59 ml/min/1.73m2 and UACR 30‐300 mg/g, or eGFR ≥60 and UACR >300 mg/g) and very high risk (eGFR <30 ml/min/1.73m2 with any UACR, eGFR 30‐44 and UACR 30‐300 mg/g, or eGFR 45‐59 ml/min/1.73m2 and UACR >300 mg/g). A Cox proportional hazards model was used to investigate the consistency of treatment effect across subgroups. RESULTS: Among 7020 participants, baseline eGFR and UACR measurements were available for 6952 patients (99%; EMPA, n=4635; PBO, n=2317). The proportions of participants in the low, moderately increased, high and very high risk KDIGO categories at baseline were 47%, 29%, 15% and 8% respectively. Median observation time was 3.1 years. The observed benefits of EMPA vs PBO on 3‐point MACE, CV death, and HHF were consistent across KDIGO risk categories (Figure). CONCLUSIONS: EMPA, given in addition to standard of care, reduced CV outcomes and mortality in patients with T2DM and established CV disease irrespective of KDIGO risk category at baseline, suggesting that empagliflozin may reduce CV disease in early as well as late stages of CKD. (Figure presented).