Influence of neprilysin inhibition on the efficacy and safety of empagliflozin in patients with chronic heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Packer, M (Author) Other; Anker, SD (Author) Other; Butler, J (Author) Other; Filippatos, G (Author) Other; Ferreira, JP (Author) FMUP; Pocock, SJ (Author) Other; Rocca, HB (Author) Other; Janssens, S (Author) Other; Tsutsui, H (Author) Other; Zhang, J (Author) Other; Brueckmann, M (Author) Other; Jamal, W (Author) Other; Cotton, D (Author) Other; Iwata, T (Author) Other; Schnee, J (Author) Other; Zannad, F (Author) Other

Journal

Title: European Heart Journal

Vol. 42

Pages: 671-680

ISSN: 0195-668X

Publisher: Oxford University Press

Other information

Authenticus ID: P-00V-8QG

DOI: 10.1093/eurheartj/ehaa968

Abstract (EN): <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Aims</jats:title> <jats:p>We evaluated the influence of sacubitril/valsartan on the effects of sodium-glucose cotransporter 2 (SGLT2) inhibition with empagliflozin in patients with heart failure and a reduced ejection fraction.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and results</jats:title> <jats:p>The EMPEROR-Reduced trial randomized 3730 patients with heart failure and an ejection fraction ¿40% to placebo or empagliflozin (10¿mg/day), in addition to recommended treatment for heart failure, for a median of 16¿months. A total of 727 patients (19.5%) received sacubitril/valsartan at baseline. Analysis of the effect of neprilysin inhibition was 1 of 12 pre-specified subgroups. Patients receiving a neprilysin inhibitor were particularly well-treated, as evidenced by lower systolic pressures, heart rates, N-terminal prohormone B-type natriuretic peptide, and greater use of cardiac devices (all P¿<¿0.001) when compared with those not receiving sacubitril/valsartan. Nevertheless, when compared with placebo, empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure in patients receiving or not receiving sacubitril/valsartan [hazard ratio 0.64 (95% CI 0.45¿0.89), P¿=¿0.009 and hazard ratio 0.77 (95% CI 0.66¿0.90), P¿=¿0.0008, respectively, interaction P¿=¿0.31]. Empagliflozin slowed the rate of decline in estimated glomerular filtration rate by 1.92¿±¿0.80¿mL/min/1.73 m2/year in patients taking a neprilysin inhibitor (P¿=¿0.016) and by 1.71¿±¿0.35¿mL/min/1.73 m2/year in patients not taking a neprilysin inhibitor (P¿<¿0.0001), interaction P¿=¿0.81. Combined inhibition of SGLT2 and neprilysin was well-tolerated.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>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.</jats:p> </jats:sec>

Language: English

Type (Professor's evaluation): Dissemination