title: Serelaxin in acute heart failure: Most recent update on clinical and preclinical evidence.
abstract: Heart failure continues to be a widely prevalent disease across the world, affecting millions of Americans annually. Acute heart failure (AHF) has a substantial effect on rising healthcare costs and is one of the major causes of morbidity and mortality. The search for new drugs for symptom relief and to improve long-term outcomes in heart failure has led to development of serelaxin, a recombinant human relaxin-2 hormone. Relaxin was discovered in pregnancy, but eventually found to have a number of other physiological actions, not only in pregnancy, but also in nonpregnant women and men. The actions of serelaxin are primarily via nitric oxide, leading to the observed vasodilatory effects, and increase in renal plasma flow. It has also been found to increase expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2 and MMP-9. The antifibrotic and antiinflammatory effects of the drug also play a role in heart failure. In Phase II studies, serelaxin has shown reduction in pulmonary arterial pressure, pulmonary capillary wedge pressure, and NT-proBNP. The recently published results of the RELAX-AHF, a phase III clinical trial on serelaxin, has opened new avenues into our understanding of its effects in heart failure. The trial showed improvement in short-term dyspnea scores and 180-day mortality, but, interestingly, failed to show any improvement of the secondary endpoints of death or readmission at 60 days. Ongoing Phase III trials like RELAX-AHF-2 and RELAX-AHF-ASIA would explain these data better and improve understanding of the use of serelaxin in clinical practice. This article summarizes the most updated published preclinical and clinical study data on serelaxin, including pharmacokinetic, pharmacodynamic, safety studies in hepatic, renal impaired patients, Phase II and Phase III trials.
authors.affiliation: Department of Cardiovascular Medicine, St. Vincent Charity Medical Center, A Teaching Hospital affiliated to Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Raktim Kumar
authors.initials: RK
authors.lastname: Ghosh
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Kinjal
authors.initials: K
authors.lastname: Banerjee
authors.affiliation: Department of Internal Medicine, St. Vincent Charity Medical Center, A Teaching Hospital affiliated to Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Ramyashree
authors.initials: R
authors.lastname: Tummala
authors.affiliation: Department of Internal Medicine, St Francis Hospital and Medical Center, Hartford, CT, USA.
authors.forename: Somedeb
authors.initials: S
authors.lastname: Ball
authors.affiliation: Department of Internal Medicine, St. Vincent Charity Medical Center, A Teaching Hospital affiliated to Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Ravakhah
authors.affiliation: Department of Cardiovascular Medicine, St. Vincent Charity Medical Center, A Teaching Hospital affiliated to Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Anjan
authors.initials: A
authors.lastname: Gupta
mesh_terms: D000208:Acute Disease; D000818:Animals; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D011994:Recombinant Proteins / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D012065:Relaxin / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D011994:Recombinant Proteins; C577649:serelaxin protein, human; D012065:Relaxin
keywords: PRE-RELAX-AHF; RELAX-AHF-2; RELAX-AHF-ASIA; RELAX-REPEAT; Relaxin-2; Serelaxin in hepatic impairment; Serelaxin in renal impairment