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Learning a lesson from mother nature to improve HF outcomes

Heart Failure 2016 Congress News

John R. Teerlink, Veterans Affairs Medical Center, University of California San Francisco, USA

Late Breaking Trials I: Focus on acute heart failure; 21 May, 14:15–15:45; London

The results of a randomised trial presented today will put the safety and tolerability of repeated use of a novel drug intended to reduce in-hospital worsening heart failure and mortality in heart failure patients under the spotlight.

The high heart failure rehospitalisation rates, up to 30%–40% over 6 months, mean that patients may need to receive the same medications repeatedly. Consequently, “the issue of recurrent administration of acute heart failure therapies in heart failure is very important,” noted John R. Teerlink (Veterans Affairs Medical Center, University of California San Francisco, USA), who will present the current analysis this afternoon.

The study is a phase IIb multi-centre, double-blind, placebo-controlled trial of the recombinant relaxin hormone serelaxin, in which patients with compensated heart failure treated with standard of care were randomised to 3-sequential 48-hour intravenous infusions of 30 µg/kg/day or placebo in a 2:1 ratio at baseline and weeks 4 and 8.

The inspiration for serelaxin came, Dr Teerlink observed, by “learning a lesson from mother nature”. Relaxin is ubiquitous in mammals and, while it has different effects in different animals, it is predominantly associated with preparing for pregnancy.

“In humans, relaxin levels go up almost immediately after implantation and remain elevated…and seem to be related to preparing the mother’s haemodynamics and cardiovascular and renal system for the extra demands of pregnancy,” said Dr Teerlink.

He added: “Interestingly, when you say you need to open up the blood vessels and make them more able to deal with higher volumes of blood, when you need to make the kidneys work better and to deal with this extra congestion, thats exactly what you want to have happen in acute heart failure.”

Serelaxin has been examined in the dose–finding Pre-RELAX-AHF study, [1] and the phase III RELAX-AHF, [2] which showed that it was associated with dyspnoea relief and improvements in worsening heart failure, and suggested improved survival in patients with acute heart failure.

The primary outcome of the current study is to determine the number of patients who develop anti-serelaxin antibodies at any time up the final follow-up at week 16, while secondary objectives included other measures of possible serelaxin immunogenicity and the safety and tolerability of infusions.

As Dr Teerlink noted, if repeat doses of serelaxin are shown to be safe and well-tolerated, the next, intriguing question is: “If we give this drug frequently as an outpatient, can we prevent rehospitalisations?”


  1. Teerlink JR, Metra M, Felker GM et al. Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet 2009; 373: 1429–1439.
  2. Teerlink JR, Cotter G, Davison BA et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 2013; 381: 29–39.

View the session programme and access the resources on SP&P