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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