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).
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.
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)
Januzzi et al. (Wed,) conducted a 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).