title: Ularitide for the treatment of acute decompensated heart failure: from preclinical to clinical studies.
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.
authors: Department of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany s.anker@cachexia.de.
authors: Stefan D
authors: SD
authors: Anker
authors: Medical University, Wroclaw, Poland.
authors: Piotr
authors: P
authors: Ponikowski
authors: Department of Cardiology, Kerckhoff-Klinik, Bad Nauheim, Germany.
authors: Veselin
authors: V
authors: Mitrovic
authors: Emergency Medicine, Baylor College of Medicine, Houston, TX, USA.
authors: W Frank
authors: WF
authors: Peacock
authors: Athens University Hospital Attikon, Athens, Greece.
authors: Gerasimos
authors: G
authors: Filippatos
mesh_terms: D000208:Acute Disease; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004232:Diuretics; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor
keywords: Acute decompensated heart failure; Diuresis; Guanylate cyclase; Natriuresis; Ularitide; Vasodilation