Aim: Patients hospitalized for acute heart failure (AHF) differ with respect of many clinical characteristics which may influence their prognosis and response to treatment. We have assessed possible differences in the effects of serelaxin on dyspnoea relief, 60 Day outcomes and 180 Day mortality across patient subgroups in the RELAX-AHF trial.
Methods And Results: Subgroups were based on pre-specified covariates (age, sex, race, geographic region, estimated glomerular filtration rate, time from presentation to randomization, baseline systolic blood pressure, history of diabetes, atrial fibrillation, ischaemic heart disease, cardiac devices, i.v. nitrates at randomization). Other covariates which may modify the efficacy of AHF treatment were also analysed. Subgroup analyses did not show any difference in the effects of serelaxin vs. placebo on dyspnoea relief or on the incidence of cardiovascular death or rehospitalizations for heart failure or renal failure at 60 days. Nominally significant interactions between some patient subgroups and the effects of serelaxin on 180 days cardiovascular and all-cause mortality were noted but should be interpreted cautiously due to the number of comparisons and the low incidence of deaths in the subgroups at lower risk.
Conclusion: The effects of serelaxin vs. placebo appeared to be similar across subgroups of patients in RELAX-AHF.
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http://dx.doi.org/10.1093/eurheartj/eht371 | DOI Listing |
Eur J Heart Fail
December 2024
Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Aims: Serelaxin is recombinant human relaxin-2, a hormone responsible for haemodynamic adaptations and organ protection in pregnancy. In the RELAX-AHF trial, serelaxin demonstrated reductions in cardiac, renal and hepatic damage. In RELAX-AHF-2, organ damage-related biomarkers were assessed in a biomarker substudy.
View Article and Find Full Text PDFExpert Opin Investig Drugs
December 2024
Cardiology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
Introduction: Acute failure is a critical condition, encompassed by the sudden or progressive onset of symptoms or signs of congestion. The treatment strategies available are mainly supportive and do not improve mortality or long-term outcomes. Therefore, there is a need for alternative novel treatment strategies.
View Article and Find Full Text PDFEur J Heart Fail
November 2024
Cardiology, ASST Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
Aims: Acute heart failure (AHF) is a major cause of hospitalizations and death in the elderly. However, elderly patients are often underrepresented in randomized clinical trials. We analysed the impact of age on clinical outcomes and response to treatment in patients enrolled in Relaxin in Acute Heart Failure (RELAX-AHF-2), a study that included older patients than in previous AHF trials.
View Article and Find Full Text PDFNephrol Dial Transplant
December 2024
Department of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada.
Background: Volenrelaxin is a half-life-extended recombinant human relaxin protein developed for improving kidney perfusion and cardiorenal function. This study assessed the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of volenrelaxin following single- and multiple-ascending doses (SAD and MAD) administration.
Methods: In this Phase 1, four-part, randomized, double-blinded, placebo-controlled SAD and MAD study in healthy participants, SAD participants (n = 56) received an intravenous or subcutaneous dose of volenrelaxin or placebo in a dose-ascending manner.
Biochem Pharmacol
May 2024
Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain.
Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats.
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