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Increase in BNP in Response to Endothelin-Receptor Antagonist Atrasentan Is Associated With Incident Heart Failure

J David Smeijer1, Jeroen Koomen1, Donald E Kohan2

  • 1Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.

JACC. Heart Failure
|June 30, 2022
PubMed

Insights

Atrasentan reduced kidney failure risk in type 2 diabetes and CKD patients. Early B-type natriuretic peptide (BNP) increases predicted heart failure (HF) risk, suggesting BNP monitoring is crucial during atrasentan treatment.

Area of Science:

  • Nephrology
  • Cardiology
  • Endocrinology

Background:

  • Atrasentan, an endothelin receptor antagonist, demonstrated nephroprotective effects in the SONAR trial for patients with type 2 diabetes mellitus and chronic kidney disease (CKD).
  • However, a numerically higher incidence of heart failure (HF) hospitalizations was observed in the atrasentan arm.

Purpose of the Study:

  • To investigate whether early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment can predict the risk of HF hospitalization.
  • To identify potential biomarkers for HF risk stratification in patients receiving atrasentan.

Main Methods:

  • Participants with type 2 diabetes and CKD underwent an open-label enrichment phase with atrasentan (0.75 mg/day).
  • Patients without significant fluid retention were randomized to atrasentan or placebo.
  • Cox proportional hazards regression analyzed the association between baseline/early BNP changes, body weight, and HF hospitalization risk.

Main Results:

  • Higher baseline BNP and a greater percentage increase in BNP during enrichment were significantly associated with increased HF risk.
  • Body weight changes did not correlate with HF hospitalization.
  • Excluding patients with a ≥25% BNP increase attenuated the HF risk associated with atrasentan, while preserving its nephroprotective benefits.

Conclusions:

  • Baseline BNP levels and early BNP dynamics during atrasentan treatment are predictive of HF hospitalization risk in patients with type 2 diabetes and CKD.
  • Monitoring natriuretic peptides is essential upon initiating atrasentan to manage potential cardiovascular risks.
  • These findings aid in refining patient selection and monitoring strategies for atrasentan therapy.
Abstract

Keywords:
atrasentanchronic kidney diseaseendothelin receptor antagonistheart failuretype 2 diabetes mellitus

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