RELAXin in Acute Heart Failure-2 - RELAX-AHF-2

Contribution To Literature:

The RELAX-AHF-2 trial failed to show that serelaxin was superior to placebo at improving outcomes in acute heart failure.


The goal of this trial was to assess safety and efficacy of serelaxin compared with placebo in reducing cardiovascular (CV) mortality in patients presenting with acute heart failure. Serelaxin is a recombinant form of relaxin-2, which is a vasodilating hormone.

Study Design

Patients were randomly assigned in a 1:1 ratio to receive either intravenous (IV) serelaxin 30 μg/kg per day (n = 3,274) or placebo (n = 3,271).

  • Total number of enrollees: 6,545
  • Duration of follow-up: 180 days
  • Mean patient age: 73 years
  • Percentage female: 40%
  • Percentage with diabetes: 46%
  • Ejection fraction: 40%
  • New York Heart Association class: 1 month prior to admission: III (46%), IV (11%)

Inclusion criteria:

Hospitalized for acute heart failure:

  • Dyspnea at rest or with minimal exertion
  • Pulmonary congestion on chest radiograph
  • B-type natriuretic peptide (BNP) ≥500 pg/ml or N-terminal pro-BNP ≥2000 pg/ml
  • Received ≥40 mg IV furosemide (or equivalent) at any time between admission to emergency services (either ambulance or hospital, including the emergency department) and the start of screening for the study
  • Systolic blood pressure ≥125 mm Hg
  • Impaired renal function on admission (estimated glomerular filtration rate [eGFR] 25-75 ml/min/1.73 m2)
  • Randomized within 16 hours from presentation
  • Age ≥18 years of age
  • Body weight <160 kg

Exclusion criteria:

  • Current or planned treatment with any IV therapies or mechanical support (except IV diuretics or IV nitrates if systolic blood pressure >150 mm Hg at screening)
  • Clinical evidence of acute coronary syndrome within 30 days prior to enrollment
  • AHF due to significant arrhythmias
  • Dyspnea due to noncardiac causes
  • Chronic obstructive pulmonary disease requiring daily steroids
  • Systolic BP >180 mm Hg or persistent heart rate >130 bpm
  • eGFR of <25 ml/min/1.73 m2 and/or those receiving current or planned dialysis or ultrafiltration

Principal Findings:

  • Primary efficacy endpoint, CV mortality at 180 days for serelaxin vs. placebo: 8.7% vs. 8.9% (p = 0.77)
  • Worsening heart failure at 5 days: 6.9% vs. 7.7% (p = 0.19)

Secondary endpoints, for serelaxin vs. placebo:

  • All-cause mortality: 11.2% vs. 11.9% (p = 0.39)
  • Median length of index hospital stay: 6.8 vs. 6.9 days (p = 0.56)
  • Safety: Hypotension: 2.4% vs. 2.0%, hypokalemia: 8.1% vs. 7.5% (p > 0.05)


Among patients admitted with acute heart failure, a 48-hour infusion of serelaxin was not effective. This medication neither reduced death from cardiovascular causes at 180 days, nor did it reduce the incidence of short-term worsening heart failure.


Metra M, Teerlink JR, Cotter G, et al., on behalf of the RELAX-AHF-2 Committees Investigators. Effects of Serelaxin in Patients With Acute Heart Failure. N Engl J Med 2019;381:716-26.

Teerlink JR, Voors AA, Ponikowski P, et al. Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX-AHF-2 study. Eur J Heart Fail 2017;19:800-9.

Presented by Dr. John R. Teerlink at the ESC World Congress on Acute Heart Failure, April 29, 2017, Paris, France.

Clinical Topics: Heart Failure and Cardiomyopathies, Statins, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Atrial Natriuretic Factor, Biological Markers, Dyspnea, Furosemide, Glomerular Filtration Rate, Heart Failure, Hypokalemia, Hypotension, Length of Stay, Natriuretic Peptide, Brain, Physical Exertion, Relaxin, Vasodilator Agents

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