The following are 10 key points to remember from this JACC Heart Failure (HF) Position Paper. The authors queried the Aggregate Analysis of ClinicalTrials.gov (AACT) database to identify all HF trials that used B-type natriuretic peptide (BNP) levels or its N-terminal pro-peptide equivalent N-terminal pro–BNP (NT-proBNP) as inclusion or exclusion criteria. They reviewed and compared trial characteristics in addition to summary data. Finally, the authors provided recommendations on best practices to incorporating BNP or NT-proBNP in clinical trials.

1. Of 3,446 HF trials, 365 completed trials used natriuretic peptides (NPs) as an inclusion or exclusion criterion. There was significant heterogeneity in cut-points used.
2. Levels of BNP and NT-proBNP varied significantly according to clinical characteristics such as age, gender, body mass index (BMI), and kidney function. Only a minority of trials (17%) adjusted NP enrollment criteria according to clinical characteristics.
3. BNP and NT-proBNP levels as enrollment criteria in clinical trials help maximize the probability of enrolling patients with high-risk disease; or in the case of HF with preserved ejection fraction (HFpEF), patients with the correct diagnosis.
4. NP levels as enrollment criteria are objective, reproducible, and not driven by cultural or process of care factors, compared to hospitalization for HF.
5. Amongst patients with chronic HFpEF, a threshold of ≥35 pg/ml for BNP and 125 pg/ml for NT-proBNP should be considered.
6. Amongst patients with acute HF, a BNP concentration of 100 pg/ml has reasonable sensitivity for acute HF and an NT-proBNP concentration <300 pg/ml excludes acute HF with a negative predictive value of 99%. Age-related cut-points of 450, 900, and 1800 pg/ml for ages <50, 50–75, and >75 years, respectively, for NT-proBNP have high sensitivity and specificity for acute HF.
7. BNP and NT-proBNP levels can be used to identify patients at risk for HF, in order to test prevention strategies. Cut-offs are significantly lower than those used for prevalent HF.
8. NP enrollment thresholds should be increased by 20-30% for the following populations: patients with atrial fibrillation and those ages >75 years. Enrollment criteria for patients with kidney disease should be doubled: 200 pg/ml for BNP and 1200 for NT-proBNP.
9. NP enrollment thresholds should be decreased 20-30% for black patients, and patients with BMI >30 kg/m².
10. BNP should not be used in patients on neprilysin inhibitors. NT-proBNP can be used instead.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Atrial Fibrillation, Body Mass Index, Geriatrics, Heart Failure, Kidney Diseases, Natriuretic Peptide, Brain, Natriuretic Peptides, Neprilysin, Peptide Fragments, Secondary Prevention, Stroke Volume

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