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

Aug 23, 2019
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Presenter/Author:
John R. Teerlink, MD, FACC
Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC ; Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Novartis Pharma
Date Presented:
04/29/2017
Date Published:
08/22/2019
Date Updated:
08/23/2019
Original Posted Date:
05/08/2017
References

Contribution To Literature:

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

Description:

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)

Interpretation:

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.

References:

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.

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


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