According to findings in a study published in the Journal of the American College of Cardiology: Heart Failure, researchers indicated that there were no reports of significant increases in overall BNP concentrations in patients HFrEF treated with Sac/Val. Additionally, patients demonstrated increases in urinary cyclic guanosine monophosphate (ucGMP) regardless of the trajectory of BNP change.

The objective of the study was to evaluate the changes in BNP among patients with HFrEF treated with Sac/Val, according to standard prescribing information. In the study, researchers conducted a pooled analysis of two 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) and Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes (PROVE-HF).

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

The researchers indicated that prior to Sac/Val 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, about 50% of the study participants reported a decline in BNP concentrations.

The researchers noted that there was no correlation between Sac/Val dose and change in BNP levels. Any change in BNP concentrations was linked directly with changes in NT-proBNP concentrations (P <.001), which diminished by -30% and -32% at Weeks 4 and 12, respectively (P <.001 for both). In contrast, change in BNP concentrations was weakly correlated with change in ucGMP (P <.001). Increases in ucGMP levels were noticed regardless of whether BNP concentrations were reduced (+11%), unchanged (+34%), or increased (+57%).

The authors wrote, "This study of individuals treated with Sac/Val based on current regulatory approval in the United States found that BNP does not uniformly increase in response to treatment of Sac/Val, with no overall change to weeks 4 and 12. This is most likely caused by some BNP increase because of neprilysin inhibition that is off-set by reduction in its production caused by unloading. Thus, clinicians can expect a difference in biomarker changes of about 30% for BNP compared to NT-proBNP, and importantly, disease status seems to be the main driver of changes of both biomarkers as the 2 natriuretic peptides correlate directionally very closely."

The authors concluded that in this pooled analysis of patients with HFrEF with standard indications for Sac/Val treatment, there was no significant overall increase in BNP concentrations, and patients demonstrated increase in ucGMP regardless of the trajectory of BNP change.

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