Clinical Implications of NT-proBNP trajectory following Sacubitril/Valsartan initiation

Abstract Introduction Serum N-terminal pro–B-type natriuretic peptide (NT-proBNP) values after initiating Sacubitril/Valsartan is considered as a favorable prognostic factor, and widely used for risk stratification in patients with heart failure (HF). However, the relationship between the trajectory of serially measured NT-proBNP values and cardiovascular events in patients with HF who are treated with Sacubitril/Valsartan remains uncertain. Purpose This study aimed to reveal the prognostic association of an NT-proBNP trajectory after initiating Sacubitril/Valsartan and subsequent cardiovascular outcomes. Methods and Results A Japanese nationwide multicenter study was conducted on HF patients who initiated Sacubitril/Valsartan. Out of the 995 patients enrolled, we excluded 561 patients who were undergoing assessment of BNP or who lacked a complete set of NT-proBNP measurement. Finally, 434 patients included this study, and were divided into three groups based on NT-proBNP trajectory as follows; the ‘sustained-responder’ group (n = 129, 30%) : which exhibited a reduction of NT-proBNP by ≥10% at 1 month and further reduction of ≥10% at 3 months; and the ‘transient-responder’ group (n = 161, 37%), with ≥10% reduction at 1 month but not at 3 months; and the ‘non-responder’ group (n = 144, 33%), which did not achieve ≥10% reduction at 1 month. The mean age was 68 years, with females comprising 29%. In the ‘sustained-responder’ group, the age was significantly younger, and the duration of heart failure was significantly shorter. There were no significant differences in the mean systolic blood pressure, mean Sacubitril/Valsartan dose at each measurement points among the 3 groups. During follow-up of 456 (IQR, 371-549) days, the primary endpoint, which was either cardiovascular death or hospitalization of HF occurred in 78 of 434 patients (18%). The Kaplan-Meier analysis showed that the ‘sustained responder’ group experienced significantly lower event rate among the 3 groups (Log-rank p<.001). Additionally, an analysis that set a landmark time at 3 months post-initiation of Sacubitril/Valsartan showed that the ‘sustained-responder’ group experienced significantly fewer events than the ‘transient-responder’ group (Log-rank p=0.039) (Figure.1). Also, the ‘sustained responder’ was observed to have a better prognosis in a subgroup with LVEF<50%, but not in patients with LVEF ≥50%. (p value for interaction=0.035) (Figure.2). Conclusions This study revealed that sustained reduction of NT-proBNP was associated with a reduced risk of cardiovascular death or hospitalization for HF. The periodic NT-proBNP monitoring and the patterns of NT-proBNP during treatment with Sacubitril/Valsartan may be helpful in optimizing HF therapy and understanding the prognosis of HF.Figure.1Figure.2