The following is a summary of “Influence of NT-proBNP on Efficacy of Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction” published in the December 2022 issue of Heart Failure by Myhre et al.
In heart failure, NT-proBNP (N-terminal pro-B-type natriuretic peptide) is measured for diagnosis and prognosis (HF). There may be treatment response heterogeneity based on baseline NT-proBNP levels, according to previous clinical trials of patients with heart failure with slightly decreased ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF). The goal of this research was to compare the treatment impact of dapagliflozin in patients with HFrEF and HFpEF based on their NT-proBNP levels at baseline. Dapagliflozin was evaluated in a randomized, placebo-controlled trial in patients with heart failure with a reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF), and this analysis was performed as a post hoc analysis.
The presence of an elevated NT-proBNP level was required for inclusion (≥300 ng/L for non-AFF; ≥600 ng/L for AFF). Quantitative and qualitative analyses were performed on NT-proBNP levels at baseline using a quartile system and a continuous analysis method. The major composite outcome was death from cardiovascular causes or a worsening of HF symptoms. The median baseline concentration of NT-proBNP was 716 (Q1-Q3: 469-1,280) ng/L for non-AFF patients and 1,399 (Q1-Q3: 962-2,212) ng/L for AFF patients among the 6,262 patients included (mean: 71.7 years and 3,516 [56%] men). Independent of AFF status, there was a linear relationship between increasing NT-proBNP levels and increased risk of the major outcome (Q4 vs. Q1: 3.46 [95% CI: 2.48-4.22]; P< 0.001), with the HR for log2 pro-BNP being 1.53.
Dapagliflozin was found to be clinically beneficial regardless of baseline NT-proBNP concentration (P value for interaction = 0.40 by quartiles and = 0.19 consistently for the primary outcome), and the absolute risk reduction was consequently greater with higher NT-proBNP concentrations. Similarly, across all quartiles of NT-proBNP, dapagliflozin’s effect on health status and safety was constant. There is no difference in the safety or efficacy of dapagliflozin between patients with HFrEF and HFpEF with respect to their baseline NT-proBNP concentrations, although the absolute benefit is expected to be the largest in patients with higher NT-proBNP concentrations.