Efficacy and safety of serelaxin when added to standard of care in patients with acute heart failure: results from a PROBE study, RELAX‐AHF‐EU

• Published in: European journal of heart failure 2019-03, Vol.21 (3), p.322-333
• Main Authors: Maggioni, Aldo P., López‐Sendón, José, Nielsen, Olav W., Hallén, Jonas, Aalamian‐Mattheis, Maryam, Wang, Yaqin, Ertl, Georg
• Format: Article
• Language: English
• Subjects: Acute Disease; Acute heart failure; Aged; Cardiovascular Agents - administration & dosage; Cardiovascular Agents - adverse effects; Cause of Death; Death; Double-Blind Method; Drug Monitoring - methods; Europe; Female; Heart Failure - drug therapy; Heart Failure - mortality; Heart Failure - physiopathology; Humans; Infusions, Intravenous; Male; Middle Aged; Mortality; PROBE; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Rehospitalisation; Relaxin - administration & dosage; Relaxin - adverse effects; Risk Adjustment; Serelaxin; Standard of Care; Treatment Outcome; Worsening heart failure
• ISSN: 1388-9842; 1879-0844
• DOI: 10.1002/ejhf.1368

Aim Serelaxin is a recombinant human relaxin‐2 hormone, which confers receptor‐mediated vasodilatation in a tissue‐specific fashion. The RELAX‐AHF‐EU study assessed the effect of serelaxin when added to standard‐of‐care (SoC) therapy on worsening heart failure (WHF)/all‐cause death through Day 5 in patients hospitalised for acute heart failure (AHF) in Europe. Methods and results This multicentre, prospective, randomised, open‐label, blinded‐endpoint validation study enrolled hospitalised AHF patients and randomised (2:1) eligible patients (mild‐to‐moderate renal impairment and systolic blood pressure ≥ 125 mmHg) within 16 h of presentation with signs/symptoms of AHF, to receive 48 h intravenous infusion of 30 μg/kg/day serelaxin + SoC or SoC alone. The primary endpoint was adjudicated WHF/all‐cause death through Day 5. Of 3183 patients targeted, 2666 were randomised when the study was terminated early by the sponsor due to the neutral results of the pivotal RELAX‐AHF‐2 study. Adjudicated WHF/all‐cause death through Day 5 was significantly reduced in the serelaxin + SoC vs. SoC group (5.0% vs. 6.9%; hazard ratio 0.71; 95% confidence interval 0.51–0.98; P = 0.0172) (absolute risk reduction 1.9%, number needed to treat 53). The difference between treatment groups was not significant for WHF/all‐cause death/heart failure rehospitalisation through Day 14 and length of hospital stay. A significantly smaller proportion of patients in the serelaxin + SoC vs. SoC group experienced persistent heart failure signs/symptoms at each visit until Day 4, or renal deterioration through Day 5 (all P ≤ 0.01). Overall incidence of treatment‐emergent adverse events was comparable between treatment groups. Hypotension and decrease in haemoglobin/haematocrit were more frequent in the serelaxin + SoC group. Conclusion When added to SoC, serelaxin reduced adjudicated WHF or all‐cause death through Day 5 in AHF patients. The results from this open‐label study should be considered in the context of the totality of the double‐blind, randomised evidence on serelaxin in AHF.