Different kinetics of NT-proBNP and sST2 highlight different therapeutic pathways of sacubitril/valsartan

Type of funding sources: None.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble interleukin 1 receptor-like 1 ST2 (sST2) are biomarkers used to grade heart failure with reduced ejection fraction (HFrEF) severity. Both are potential targets of HFrEF treatment, but the first is associated with the patient’s hemodynamic status, while the second is more indicative of the inflammatory status and of myocardial fibrosis.

The aim of this study was to assess the kinetics of these biomarkers after treatment with sacubitril/valsartan in HFrEF.

We analyzed blood samples of HFrEF patients at baseline (before sacubitril/valsartan treatment), after 1, 2, 3 months (respectively after a month taking the 24/26 – 49/51 – 97/103mg b.i.d. doses), and 6 months after the maximum tolerated dose was reached (end-study).

We obtained samples from 72 HFrEF patients (age 64.0±10.5, 83% males) (Table 1). NT-proBNP and sST2 values progressively and significantly reduced up to 37% and 16%, respectively, with a greater reduction for NT-proBNP (p<0.001). Specifically, NT-proBNP reduced from 1144 [593-2586] to 743 [358-1524] pg/mL and sST2 from 27.3 [20.5-35.0] to 23.1 [15.9-30.7] ng/mL, p for trend <0.001 in both cases). The reduction of the two biomarkers over time occurred with statistically significant different kinetics: deferred for sST2 and faster for NT-proBNP (Figure 1). No significant changes in renal function and potassium levels were recorded.

These findings suggest that, in HF patients, sacubitril/valsartan effects on the cardiovascular system share a double pathway: a first, hemodynamic, faster pathway and a second, non-hemodynamic anti-inflammatory, delayed one. Both likely contribute to the sacubitril/valsartan benefits in HFrEF.

Table 1