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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
Author(s) -
Maggioni Aldo P.,
LópezSendón José,
Nielsen Olav W.,
Hallén Jonas,
AalamianMattheis Maryam,
Wang Yaqin,
Ertl Georg
Publication year - 2019
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.1368
Subject(s) - medicine , heart failure , hazard ratio , nesiritide , clinical endpoint , confidence interval , blood pressure , cardiology , randomized controlled trial , natriuretic peptide
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.