Heart Failure Therapeutics on the Basis of a Biased Ligand of the Angiotensin-2 Type 1 Receptor Rationale and Design of the BLAST-AHF Study (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure)

G. Michael Felker*, Javed Butler, Sean P. Collins, Gad Cotter, Beth A. Davison, Justin A. Ezekowitz, Gerasimos Filippatos, Phillip D. Levy, Marco Metra, Piotr Ponikowski, David G. Soergel, John R. Teerlink, Jonathan D. Violin, Adriaan A. Voors, Peter S. Pang

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

The BLAST-AHF (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure) study is designed to test the efficacy and safety of TRV027, a novel biased ligand of the angiotensin-2 type 1 receptor, in patients with acute heart failure (AHF). AHF remains a major public health problem, and no currently-available therapies have been shown to favorably affect outcomes. TRV027 is a novel biased ligand of the angiotensin-2 type 1 receptor that antagonizes angiotensin-stimulated G-protein activation while stimulating beta-arrestin. In animal models, these effects reduce afterload while increasing cardiac performance and maintaining stroke volume. In initial human studies, TRV027 appears to be hemodynamically active primarily in patients with activation of the renin-angiotensin-aldosterone system, a potentially attractive profile for an AHF therapeutic. BLAST-AHF is an international prospective, randomized, phase IIb, dose-ranging study that will randomize up to 500 AHF patients with systolic blood pressure >= 120 mm Hg and

Original languageEnglish
Pages (from-to)193-201
Number of pages9
JournalJACC. Heart failure
Volume3
Issue number3
DOIs
Publication statusPublished - Mar-2015

Keywords

  • BLAST-AHF
  • NT-proBNP
  • TRV027
  • LEFT-VENTRICULAR DYSFUNCTION
  • ACUTE MYOCARDIAL-INFARCTION
  • MULTIPLE END-POINTS
  • CLINICAL-TRIALS
  • INTRAVENOUS ENALAPRILAT
  • CARDIAC MYOCYTES
  • BETA-ARRESTINS
  • I RECEPTOR
  • PHASE-II
  • ASSOCIATION

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