Effect of empagliflozin on major heart failure outcomes and renal function in patients with heart failure with a reduced ejection fraction, with and without sacubitril/valsartan

Introduction In the EMPEROR-Reduced Trial, empagliflozin reduced cardiovascular death or HF hospitalization and slowed the progressive decline in kidney function in patients with HFrEF. We evaluated the influence of neprilysin inhibition with sacubitril/valsartan (ARNi) on the effects of SGLT2i with empagliflozin. Method The EMPEROR-Reduced trial randomized 3730patients with HF and an ejection fraction ≤ 40% to placebo or empagliflozin(10 mg/day), in addition to recommended treatment for HF, for a median of 16months. A total of 727patients (19.5%) received ARNi at baseline. Analysis of the effect of ARNi was 1 of 12 pre-specified subgroups. Results Patients receiving ARNi were particularly well-treated, as evidenced by lower systolic pressures, heart rates, NT-Pro-BNP, and greater use of cardiac devices (all P  Fig. 1 ]. Empagliflozin slowed the rate of decline in estimated glomerular filtration rate by 1.92 ± 0.80mL/min/1.73m2/year in patients taking ARNi (P = 0.016) and by 1.71 ± 0.35mL/min/1.73m2/year in patients not taking ARNi (P  Conclusion The effects on empagliflozin to reduce the risk of heart failure and renal events are not diminished in intensively treated patients who are receiving sacubitril/valsartan. Combined treatment with both SGLT2 and neprilysin inhibitors can be expected to yield substantial additional benefits.