Sacubitril/Valsartan Does Not Significantly Increase BNP Levels in Patients With HFrEF

Blood sample for BNP test
Blood sample for B-type natriuretic peptide or BNP test, cardiac marker for acute or chronic heart failure
Using pooled analysis, researchers assessed changes in B-type natriuretic peptide in patients with HFrEF being treated with sacubitril/valsartan.

No significant increase in overall B-type natriuretic peptide (BNP) concentrations was reported in patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan, according to research published in the Journal of the American College of Cardiology: Heart Failure. Patients demonstrated increases in urinary cyclic guanosine monophosphate (ucGMP) regardless of the trajectory of BNP change.

For the current study, researchers performed a pooled analysis of 2 studies: Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction (EVALUATE-HF; Identifier: NCT02874794) and Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes (PROVE-HF; Identifier: NCT02887183). Seeking to explore whether the angiotensin receptor neprilysin inhibitor sacubitril/valsartan may increase BNP concentrations, investigators evaluated changes in BNP among patients with HFrEF who received treatment with sacubitril/valsartan, per the standard prescribing information.

A total of 367 participants were enrolled in the analysis. Changes in BNP, N-terminal pro-BNP (NT-proBNP), and ucGMP levels were evaluated at baseline to week 4 and week 12. The mean age of patients was 66.5±11.1 years. Overall, 74% of the participants were men, 71% were White, and 91% were New York Heart Association functional class II or III. Duration of HF in the participants was 74.9±78.8 months; left ventricular ejection fraction was 32%±9%.

Prior to sacubitril/valsartan therapy, median BNP concentrations were 145 ng/L, with comparable levels in EVALUATE-HF and PROVE-HF (150 ng/L vs 130 ng/L, respectively). At 4 weeks and 12 weeks, median levels of BNP were 136 ng/L and 135 ng/L, respectively. No significant change in BNP concentration was observed from baseline to week 4 (0%; P=.36) or from baseline to week 12 (+1%; P=.97). By week 12, approximately 50% of the study participants reported a decline in BNP concentrations.

No association was reported between sacubitril/valsartan dose and change in BNP levels. Any change in BNP concentrations was associated directly with changes in NT-proBNP concentrations (P< .001), which decreased by -30% and -32% at weeks 4 and 12, respectively (P<.001 for both). In contrast, change in BNP concentrations was only weakly associated with change in ucGMP (P<.001). Increases in ucGMP levels were seen regardless of whether BNP concentrations were decreased (+11%), unchanged (+34%), or increased (+57%).

“…[In patients] with large reduction of NT-proBNP, reduced production of BNP exceeds the effect of neprilysin inhibition on BNP degradation and a drop in the marker is observed,” the investigators noted. “Patients treated with [sacubitril/valsartan] demonstrate increase in ucGMP regardless of the BNP trajectory.” 

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Myhre PL, Prescott MF, Murphy SP, et al. Early B-type natriuretic peptide change in HFrEF patients treated with sacubitril/valsartan: a pooled analysis of EVALUATE-HF and PROVE-HF. J Am Coll Cardiol HF. Published online January 12, 2022.