{"doi":"10.1016/j.jchf.2021.09.007","title":"Early B-Type Natriuretic Peptide Change in HFrEF Patients Treated With Sacubitril/Valsartan","abstract":"OBJECTIVES: This study assessed changes in B-type natriuretic peptide (BNP) among patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (Sac/Val) according to standard prescribing information. BACKGROUND: Through inhibition of neprilysin, Sac/Val may increase BNP concentrations. METHODS: In an individual patient analysis from the EVALUATE-HF (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction) (n = 221) and the PROVE-HF (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes) (n = 146) studies, we examined changes in BNP, N-terminal pro-BNP (NT-proBNP), and urinary cyclic guanosine monophosphate (ucGMP) from baseline to week 4 and week 12. RESULTS: Median (IQRs) concentration of BNP at baseline, week 4, and week 12 were 145 [IQR: 55-329], 136 [IQR: 50-338], and 135 [IQR: 51-299] ng/L, respectively. There was no significant change from baseline to week 4 (0% [-30% to +41%]; P = 0.36) or week 12 (+1% [-36% to +50%]; P = 0.97). By week 12, one-half of the study participants had a BNP decline. There was no association between Sac/Val dose and BNP changes. Change in BNP was directly associated with change in NT-proBNP (rho: = 0.81; P < 0.001), which decreased by -30% (-50% to -8%) and -32% (-54% to -1%) to weeks 4 and 12 (P < 0.001 for both). In contrast, change in BNP was only weakly associated with change in ucGMP (rho: = 0.19; P < 0.001). Increases in ucGMP were observed regardless of whether BNP was decreased (+11% [-34% to +115%]), unchanged (+34% [-15% to +205%]), or increased (+57% [-12% to +14%]). CONCLUSIONS: 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. (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction [EVALUATE-HF]; NCT02874794) (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).","journal":"JACC Heart Failure","year":2022,"id":252299,"datarank":1.0355018733258659,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.558793798773674,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.558793798773674,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":18,"citers_with_citation_signal":15,"citers_with_endowment":15,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02887183","NCT02874794"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":273235,"name":"Margaret F. Prescott","orcid":null,"position":1,"is_corresponding":false},{"id":232172,"name":"Sean Murphy","orcid":"0000-0002-5928-5974","position":2,"is_corresponding":false},{"id":233711,"name":"James C. Fang","orcid":"0000-0003-2427-9504","position":3,"is_corresponding":false},{"id":337721,"name":"Gary F. Mitchell","orcid":"0000-0001-5643-3145","position":4,"is_corresponding":false},{"id":354495,"name":"Jonathan H. Ward","orcid":"0009-0002-6739-6567","position":5,"is_corresponding":false},{"id":28286,"name":"Brian Claggett","orcid":"0000-0002-4215-9218","position":6,"is_corresponding":false},{"id":57261,"name":"Akshay S. Desai","orcid":"0000-0002-1443-0701","position":7,"is_corresponding":false},{"id":27970,"name":"Scott D. Solomon","orcid":"0000-0003-3698-9597","position":8,"is_corresponding":false},{"id":97061,"name":"James L. Januzzi","orcid":"0000-0002-8338-1798","position":9,"is_corresponding":false},{"id":262831,"name":"Peder L. Myhre","orcid":"0000-0002-5871-1804","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T00:24:46.226372Z","pmid":"35115085","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}