Physicians' Academy for Cardiovascular Education

SGLT2i reduces cardiorenal outcomes in HFrEF irrespective of baseline NT-proBNP

Prognostic Importance of NT-proBNP and Effect of Empagliflozin in the EMPEROR-Reduced Trial

Literature - Januzzi JL, Zannad F, Anker SD et al. - J Am Coll Cardiol 2021,

Introduction and methods

In patients with HFrEF, increased levels of NT-proBNP are associated with a more decompensated hemodynamic profile, higher filling pressures, greater risk for progression of adverse cardiac remodeling, hospitalization and death [1-4]. And reduction in NT-proBNP in response to treatment for HFrEF is associated with improved outcomes [1,2,5].

Following treatment with SGLT2 inhibitors in patients with T2DM (most of whom did not have HFrEF), a reduction in NT-proBNP has been observed [6]. But the effect of SGLT2 inhibitors on NT-proBNP levels in chronic HFrEF patients has not been fully explored.

Therefore, in this analysis using data of the EMPEROR-Reduced trial, it was examined 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, and whether changes in NT-proBNP after SGLT2i treatment were associated with subsequent outcomes.

In the EMPEROR-Reduced trial, HF patients with LVEF of ≤40% and NYHA class II-IV were randomized to placebo or empagliflozin. Other inclusion criteria were: recent hospitalization (within 12 months), or elevated NT-proBNP. NT-proBNP levels were measured at baseline, and at 4,12, 52 and 100 weeks. Baseline NT-proBNP measurements were available in 3728 study participants.

Main results


In this pre-specified analysis of EMPEROR-Reduced in HFrEF patients, the effect of empagliflozin on reducing the risk of outcomes was similar across NT-proBNP quartiles. Furthermore, empagliflozin reduced NT-proBNP levels and achievement of levels <1,115 pg/mL of NT-proBNP was associated with lower risk of outcomes.

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