First Clinical Experience with Intravenous Recombinant Human Relaxin in Compensated Heart Failure

Abstract

Relaxin is upregulated and plays a compensatory role in human heart failure. We therefore determined the safety of and dose response to human relaxin in stable patients with heart failure. Sixteen patients were treated with open-label intravenous relaxin in three sequential dose cohorts and monitored hemodynamically during the 24-h infusion and postinfusion periods. The safety demonstrated in group A (treatment for 8 h each with dosages equivalent to 10, 30, and 100 microg/kg/day) allowed escalation to group B (240, 480, and 960 microg/kg/day), and the highest safe dose, 960 microg/kg/day, was selected for a 24-h dosing in group C. Relaxin showed no relevant adverse effects and produced hemodynamic effects consistent with systemic vasodilation, i.e., trends toward increases in the cardiac index and decreases in pulmonary wedge pressure, without inducing hypotension. The first therapeutic use of relaxin in human heart failure demonstrated favorable hemodynamic effects and indicated that it may be of value in the treatment of this widespread disease.

Current treatments for acute heart failure: focus on serelaxin

“…There were two subjects that experienced serious adverse events related to decreased blood pressure, both in the highest-dose relaxin group. Unlike the phase I trial of stable compensated heart failure, 113,114 there was no significant improvement in renal function in the relaxin group, but there was a trend toward an increase in the percentage of subjects experiencing an increase greater than 26 µmol/L (0.29 mg/dL) at day 14, which was significant at the highest relaxin dose.…”

“…113,114 The aim of this open-label study was to determine safety, tolerability, and pharmacokinetics, as well as hemodynamic properties of intravenously administered recombinant human relaxin. The subjects were males with New York Heart Association Class II-III, left ventricular ejection fraction ,35%, and were on standard chronic heart failure medication (ARBs or ACE inhibitors, beta-blockers, diuretics, and antiplatelet treatment).…”

Serelaxin in acute heart failure. Is there a revolution?

“…В одноцентровом открытом исследовании 16 пациен-тов с ХСН вне обострения с ФВ ЛЖ менее 35% с разными дозировками препарата 4 пациента (группа А) получали инфузию серелаксина по 8 ч с дозировками 10, 30 и 100 мкг/кг/сут; 6 пациентов (группа В) -240/480/ 960 мкг/кг/сут по 8 ч и соответственно 6 оставшихся -960 мкг/кг/сут на протяжении 24 ч [11,12]. Препарат по-казал вазодилатирующий эффект -повысился сердеч-ный индекс, снизилось давление заклинивания легочной артерии, ОПСС и такой маркер, как мозговой натрийуре-тический пептид (BNP).…”

Serelaxin: A Novel Therapy for Acute Heart Failure with a Range of Hemodynamic and Non-Hemodynamic Actions

“…In a study of stable patients with compensated HF, serelaxin provided hemodynamic improvements, including reduced pulmonary capillary wedge pressure (PCWP) and systemic vascular resistance (SVR), and increased cardiac index, suggesting it may reduce cardiac overload and improve cardiac performance [41, 42]. Similarly, reductions in SVR and PCWP and increases in cardiac index have been observed with serelaxin in patients with AHF [43].…”