Januzzi, James L; Zannad, Faiez; Anker, Stefan D; Butler, Javed; Filippatos, Gerasimos; Pocock, Stuart J; Ferreira, João Pedro; Sattar, Naveed; Verma, Subodh; Vedin, Ola; +5 more... Schnee, Janet; Iwata, Tomoko; Cotton, Dan; Packer, Milton; EMPEROR-Reduced Trial Committees and Investigators; EMPEROR-Reduced Trial Committees and Investigators; (2021) Prognostic Importance of NT-proBNP and Effect of Empagliflozin in the EMPEROR-Reduced Trial. Journal of the American College of Cardiology, 78 (13). pp. 1321-1332. ISSN 0735-1097 DOI: https://doi.org/10.1016/j.jacc.2021.07.046
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Abstract
BACKGROUND: The relationship between the benefits of empagliflozin in heart failure with reduced ejection fraction (HFrEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) has not been reported. OBJECTIVES: The authors sought to evaluate the relationship between NT-proBNP and empagliflozin effects in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction). METHODS: Patients with HFrEF were randomly assigned to placebo or empagliflozin 10 mg daily. NT-proBNP was measured at baseline, 4 weeks, 12 weeks, 52 weeks, and 100 weeks. Patients were divided into quartiles of baseline NT-proBNP. RESULTS: Incidence rates for each study outcome were 4- to 6-fold higher among those in the highest versus lowest NT-proBNP quartiles (≥3,480 vs <1,115 pg/mL). Study participants with higher NT-proBNP had 2- to 3-fold total hospitalizations higher than the lowest NT-proBNP quartile. Empagliflozin reduced risk for major cardiorenal events without heterogeneity across NT-proBNP quartiles (primary endpoint Pinteraction = 0.94; renal composite endpoint Pinteraction = 0.71). Empagliflozin treatment significantly reduced NT-proBNP at all timepoints examined; by 52 weeks, the adjusted mean difference from placebo was 13% (P < 0.001). An NT-proBNP in the lowest quartile (<1,115 pg/mL) 12 weeks after randomization was associated with lower risk for subsequent cardiovascular death or heart failure hospitalization regardless of baseline concentration. Treatment with empagliflozin resulted in 27% higher adjusted odds of an NT-proBNP concentration of <1,115 pg/mL by 12 weeks compared with placebo (P = 0.01). CONCLUSIONS: In EMPEROR-Reduced, higher baseline NT-proBNP concentrations were associated with greater risk for adverse heart failure or renal outcomes, but empagliflozin reduced risk regardless of baseline NT-proBNP concentration. The NT-proBNP concentration after treatment with empagliflozin better informs subsequent prognosis than pretreatment concentrations. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).
Item Type | Article |
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Faculty and Department | Faculty of Epidemiology and Population Health > Dept of Medical Statistics |
PubMed ID | 34556318 |
Elements ID | 166380 |