Key result
Empagliflozin reduces major cardiorenal events regardless of baseline NT-proBNP and lowers levels ~13% versus placebo.
Why the study?
The relationship between the clinical benefits of empagliflozin in heart failure with reduced ejection fraction and NT-proBNP had not been reported.
Does empagliflozin reduce major cardiorenal events and lower NT-proBNP across different baseline NT-proBNP levels in patients with HFrEF?
RCT
Randomized
Does empagliflozin reduce major cardiorenal events and lower NT-proBNP across different baseline NT-proBNP levels in patients with HFrEF?
Empagliflozin provides consistent cardiorenal benefits in HFrEF regardless of baseline NT-proBNP levels and significantly lowers NT-proBNP, which correlates with improved subsequent prognosis.
Answers are grounded in this paper and cite their sources.
Empagliflozin supports broad use in HFrEF regardless of NT-proBNP; confirms consistent cardiorenal benefit with added NT-proBNP reduction.
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. 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). 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. 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). 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)
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Januzzi et al. (2021) conducted an RCT in Heart failure with reduced ejection fraction (HFrEF). Empagliflozin vs. Placebo was evaluated on Major cardiorenal events. Empagliflozin reduced the risk of major cardiorenal events regardless of baseline NT-proBNP and resulted in a 13% greater reduction in NT-proBNP compared with placebo by 52 weeks (P<0.001).
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