Ularitide for the treatment of acute decompensated heart failure: From preclinical to clinical studies

Stefan D. Anker, Piotr Ponikowski, Veselin Mitrovic, W. Frank Peacock, Gerasimos Filippatos

Research output: Contribution to journalArticlepeer-review

Abstract

The short- and long-term morbidity and mortality in acute heart failure is still unacceptably high. There is an unmet need for new therapy options with new drugs with a new mode of action. One of the drugs currently in clinical testing in Phase III is ularitide, which is the chemically synthesized form of the human natriuretic peptide urodilatin. Urodilatin is produced in humans by differential processing of pro-atrial natriuretic peptide in distal renal tubule cells. Physiologically, urodilatin appears to be the natriuretic peptide involved in sodium homeostasis. Ularitide exerts its pharmacological actions such as vasodilation, diuresis, and natriuresis through the natriuretic peptide receptor/particulate guanylate cyclase/cyclic guanosine monophosphate pathway. In animal models of heart failure as well as Phase I and II clinical studies in heart failure patients, ularitide demonstrated beneficial effects such as symptom relief and vasodilation, while still preserving renal function. Subsequently, the pivotal acute decompensated heart failure (ADHF) Phase III study, called TRUE-AHF, was started with the objectives to evaluate the effects of ularitide infusion on the clinical status and cardiovascular mortality of patients with ADHF compared with placebo. This review summarizes preclinical and clinical data supporting the potential use of ularitide in the treatment of ADHF.

Original languageEnglish
Pages (from-to)715-723
Number of pages9
JournalEuropean Heart Journal
Volume36
Issue number12
DOIs
Publication statusPublished - Mar 21 2015

Keywords

  • Acute decompensated heart failure
  • Diuresis
  • Guanylate cyclase
  • Natriuresis
  • Ularitide
  • Vasodilation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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