Natriuretic Peptides as Inclusion Criteria in Clinical Trials: A JACC: Heart Failure Position Paper

Abstract

This study investigated the use of natriuretic peptides as inclusion criteria and to develop recommendations regarding their use. B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are commonly used as inclusion criteria for heart failure (HF) clinical trials, but no consensus exists regarding their optimal use for this purpose. A comprehensive search of the Aggregate Analysis of ClincalTrials.gov database identified 3,446 HF trials. Of these, 365 recently completed or ongoing HF clinical trials (10.6%) used either BNP or NT-proBNP as inclusion criteria. A panel of experts discussed current practices and a path forward for the use of natriuretic peptides as inclusion criteria for HF trials. Significant variations existed across trials regarding which natriuretic peptide and which cutoff value were used. Overall, 43% used both natriuretic peptides, 33% used only NT-proBNP, and 24% used only BNP in determining eligibility. Studies using BNP and NT-proBNP concentrations as inclusion criteria had higher cardiovascular event rates and higher concentrations for study entry and were generally associated with higher event rates. Areas of uncertainty included use in certain patient populations in which natriuretic peptides are historically lower (e.g., black patients, obese patients, patients with HF with preserved ejection fraction) or higher (older patients, patients with atrial fibrillation). This paper discusses best practices regarding use of BNP or NT-proBNP in clinical trials and identification of gaps in medical literature, including importance of documentation in ClinicalTrials.gov studies to inform future research efforts.

Keywords: biomarkers; clinical trials; inclusion criteria; natriuretic peptides.