Serelaxin in Subgroups of Patients With Acute Heart Failure
Serelaxin in Subgroups of Patients With Acute Heart Failure
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.
Heart failure (HF) is the most important cause of hospitalization for subjects older than 65 years and these hospitalizations are associated with high mortality rates, up to 10–20% in the 6 months following discharge, and 5–15-fold higher than those of ambulatory patients with chronic HF. However, treatment of acute HF (AHF) has not changed in the recent decades and major trials with new therapies have failed to show clinically meaningful benefits.
Serelaxin is a recombinant form of human relaxin-2, a naturally occurring peptide hormone which mediates the physiological cardiovascular (CV) and renal adaptations of pregnancy. In the RELAX-AHF trial, a 48-h i.v. infusion of serelaxin to patients with AHF was associated with an improvement in dyspnoea, measured by the visual analogue scale (VAS) to Day 5, but without a significant effect on the other primary endpoint of dyspnoea assessed by the Likert scale, and no change in the two secondary endpoints related with 60-day outcomes. Cardiovascular mortality at Day 180 (a protocol-specified additional efficacy analysis) and all-cause mortality at Day 180 (a pre-specified safety endpoint) were significantly reduced by serelaxin administration, which was consistent with the trend observed in the Pre-RELAX-AHF phase II trial.
Patients hospitalized for HF are a heterogeneous population and differ with respect to many characteristics, including the triggers of acute decompensation, and comorbidities. The aim of the present study was to compare the effects of serelaxin vs. placebo on dyspnoea, 60-day outcomes and 180-day mortality, in the major subgroups of patients enrolled in the RELAX-AHF trial.
Abstract and Introduction
Abstract
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.
Introduction
Heart failure (HF) is the most important cause of hospitalization for subjects older than 65 years and these hospitalizations are associated with high mortality rates, up to 10–20% in the 6 months following discharge, and 5–15-fold higher than those of ambulatory patients with chronic HF. However, treatment of acute HF (AHF) has not changed in the recent decades and major trials with new therapies have failed to show clinically meaningful benefits.
Serelaxin is a recombinant form of human relaxin-2, a naturally occurring peptide hormone which mediates the physiological cardiovascular (CV) and renal adaptations of pregnancy. In the RELAX-AHF trial, a 48-h i.v. infusion of serelaxin to patients with AHF was associated with an improvement in dyspnoea, measured by the visual analogue scale (VAS) to Day 5, but without a significant effect on the other primary endpoint of dyspnoea assessed by the Likert scale, and no change in the two secondary endpoints related with 60-day outcomes. Cardiovascular mortality at Day 180 (a protocol-specified additional efficacy analysis) and all-cause mortality at Day 180 (a pre-specified safety endpoint) were significantly reduced by serelaxin administration, which was consistent with the trend observed in the Pre-RELAX-AHF phase II trial.
Patients hospitalized for HF are a heterogeneous population and differ with respect to many characteristics, including the triggers of acute decompensation, and comorbidities. The aim of the present study was to compare the effects of serelaxin vs. placebo on dyspnoea, 60-day outcomes and 180-day mortality, in the major subgroups of patients enrolled in the RELAX-AHF trial.
