prognostic importance of BNP (B-type natriuretic peptide) and effect of Empagliflozin in the EMPEROR - Reduced Trial

Last edited 10/2021 and last reviewed 12/2021

Among patients affected by heart failure (HF) with reduced ejection fraction (HFrEF), elevated concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with more severe symptoms, worse health status, and a higher risk for hospitalization for HF or cardiovascular (CV) death (1)

• showed that with respect to the application of guideline directed medical therapy (GDMT)
  • in patients with HFrEF, those with decrease in NT-proBNP <=1000 pg/mL during GDMT had better outcomes

In a pre-specified analysis using data of the EMPEROR-Reduced trial, it was examined (2):

• whether baseline NT-proBNP had an effect on the efficacy of SGLT2 inhibitors in HFrEF
• what the effect of SGLT2 inhibitors was on levels of NT-proBNP,
• whether changes in NT-proBNP after SGLT2i treatment were associated with subsequent outcomes

Study results (2):

• treatment with empagliflozin reduced time to first events of CV death, hospitalization or the composite of both events across NT-proBNP quartiles without interaction with baseline NT-proBNP (P trend >0.05)
• use of empagliflozin reduced the risk of total hospitalizations for HF in all NT-proBNP quartiles, with no heterogeneity between groups (Ptrend=0.49). Similar results were seen for all-cause mortality
• patients had a lower risk of the primary endpoint of CV death/HF hospitalization if they had NT-proBNP of <1,115 pg/mL at week 12, regardless of baseline value of NT-proBNP
• in an adjusted model, treatment with empagliflozin resulted in a 27% (95%CI: 5.6-52.6) higher likelihood of having NT-proBNP of <1,115 pg/mL (P=0.01).
  • in those with an NT-proBNP of >= 1,115 pg/mL at baseline, treatment with empagliflozin resulted in an adjusted 35% (95CI: 17-56) higher likelihood of achieving an NT-proBNP of <1,115 pg/mL compared to the placebo group (P<0.001)

The study authors concluded (2):

• 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

Reference:

• Januzzi JL Jr, Ahmad T, Mulder H, et al. Natriuretic Peptide Response and Outcomes in Chronic Heart Failure With Reduced Ejection Fraction. J Am Coll Cardiol. 2019;74(9):1205-1217. doi:10.1016/j.jacc.2019.06.055
• Januzzi JL, Zannad F, Anker SD et al. Prognostic Importance of NT-proBNP and Effect of Empagliflozin in the EMPEROR-Reduced Trial. J Am Coll Cardiol 2021, doi.org/10.1016/jacc.2021.07.046