Increase in BNP in response to endothelin-receptor antagonist atrasentan is associated with incident heart failure

Smeijer, J. D. et al. (2022) Increase in BNP in response to endothelin-receptor antagonist atrasentan is associated with incident heart failure. JACC: Heart Failure, 10(7), pp. 498-507. (doi: 10.1016/j.jchf.2022.03.004) (PMID:35772861)

Abstract

Objectives: The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict heart failure (HF) risk. Background: The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of HF hospitalization. Methods: Participants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.75 mg/day. Participants without substantial fluid retention (>3 kg body weight increase or BNP increase to >300 pg/mL), were randomized to atrasentan 0.75 mg/day or placebo. Cox proportional hazards regression was used to assess the effects of atrasentan vs placebo on the prespecified safety outcome of HF hospitalizations. Results: Among 3,668 patients, 73 (4.0%) participants in the atrasentan and 51 (2.8%) in the placebo group developed HF (HR: 1.39; 95% CI: 0.97-1.99; P = 0.072). In a multivariable analysis, HF risk was associated with higher baseline BNP (HR: 2.32; 95% CI: 1.81-2.97) and percent increase in BNP during response enrichment (HR: 1.46; 95% CI: 1.08-1.98). Body weight change was not associated with HF. Exclusion of patients with at least 25% BNP increase during enrichment attenuated the risk of HF with atrasentan (HR: 1.02; 95% CI: 0.66-1.56) while retaining nephroprotective effects (HR: 0.58; 95% CI: 0.44-0.78). Conclusions: In patients with type 2 diabetes and CKD, baseline BNP and early changes in BNP in response to atrasentan were associated with HF hospitalization, highlighting the importance of natriuretic peptide monitoring upon initiation of atrasentan treatment. (Study Of Diabetic Nephropathy With Atrasentan [SONAR]; NCT01858532).

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John
• Authors: Smeijer, J. D., Koomen, J., Kohan, D. E., McMurray, J. J.V., Bakris, G. L., Correa-Rotter, R., Hou, F.-F., Januzzi, J. L., Kitzman, D. W., Kolansky, D. M., Makino, H., Perkovic, V., Tobe, S., Parving, H.-H., de Zeeuw, D., and Heerspink, H. J.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: JACC: Heart Failure
• Publisher: Elsevier
• ISSN: 2213-1779
• ISSN (Online): 2213-1787
• Published Online: 04 May 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First publis10(7): 498-507
• Publisher Policy: Reproduced under a Creative Commons License