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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

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.The EMPEROR-Reduced trial randomized 3730 patients with heart failure and an ejection fraction ≤40%...

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Main Authors: Packer, Milton (Author) , Anker, Stefan D (Author) , Butler, Javed (Author) , Filippatos, Gerasimos (Author) , Ferreira, Joao Pedro (Author) , Pocock, Stuart J (Author) , Rocca, Hans-Peter Brunner-La (Author) , Janssens, Stefan (Author) , Tsutsui, Hiroyuki (Author) , Zhang, Jian (Author) , Brückmann, Martina (Author) , Jamal, Waheed (Author) , Cotton, Daniel (Author) , Iwata, Tomoko (Author) , Schnee, Janet (Author) , Zannad, Faiez (Author)
Format: Article (Journal)
Language:English
Published: 7 February 2021
In: European heart journal
Year: 2021, Volume: 42, Issue: 6, Pages: 671-680
ISSN:1522-9645
DOI:10.1093/eurheartj/ehaa968
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/eurheartj/ehaa968
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Author Notes:Milton Packer, Stefan D Anker, Javed Butler, Gerasimos Filippatos, Joao Pedro Ferreira, Stuart J Pocock, Hans-Peter Brunner-La Rocca, Stefan Janssens, Hiroyuki Tsutsui, Jian Zhang, Martina Brueckmann, Waheed Jamal, Daniel Cotton, Tomoko Iwata, Janet Schnee, Faiez Zannad, for the EMPEROR-Reduced Trial Committees and Investigators
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Summary: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.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.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.
Item Description:Gesehen am 31.05.2021
Physical Description:Online Resource
ISSN:1522-9645
DOI:10.1093/eurheartj/ehaa968

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