What is the clinical evidence from this study?

Study design: RCT. Population: Acute heart failure (n=1161). Intervention: Serelaxin vs. Placebo. Primary outcome: Difference in patient-reported dyspnoea (VAS AUC to Day 5 and Likert scale) across subgroups.

September 2, 2013Open Access

Effects of serelaxin in subgroups of patients with acute heart failure: results from RELAX-AHF

Q: What does this research mean for the field?

Serelaxin demonstrates consistent effects on dyspnoea relief and 60-day outcomes compared to placebo across multiple pre-specified and post hoc patient subgroups with acute heart failure. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

Serelaxin demonstrated consistent effects on dyspnoea relief and 60-day outcomes compared to placebo across multiple pre-specified and post hoc patient subgroups with acute heart failure.

Study Design

Type

RCT (n=1,161)

Blinding

Double-blind

Randomization

Yes

Multicenter

Yes

Structured PICO

Does serelaxin improve dyspnoea and clinical outcomes across different patient subgroups in acute heart failure?

Population

1,161 patients hospitalized for acute heart failure (AHF) within 16 h of presentation, with dyspnoea at rest or minimum exertion, pulmonary congestion, BNP ≥350 ng/L or NT-proBNP ≥1400 ng/L, mild-to-moderate renal dysfunction (eGFR 30–75 mL/min/1.73 m2), SBP >125 mmHg, and treatment with at least 40 mg i.v. furosemide or equivalent.

Intervention

Serelaxin 30 μg/kg per day administered as a continuous i.v. infusion for up to 48 h.

Comparator

Matching placebo administered as a continuous i.v. infusion for up to 48 h.

Outcome

Difference in patient-reported dyspnoea quantiﬁed by the area under the curve (AUC) of the change from baseline of dyspnoea severity on a 0 to 100 mm VAS assessed from baseline to Day 5; and the proportion of patients with a moderate or marked improvement in dyspnoea at 6, 12, and 24 h assessed by a 7-level Likert scale.patient reported

The beneficial effects of serelaxin on dyspnea relief and clinical outcomes in acute heart failure were consistent across multiple pre-specified and post-hoc patient subgroups.

Limitations

Study was not powered to detect differential treatment effects across subgroups
Nominally significant interactions should be interpreted cautiously given the large number of pre-specified and post hoc analyses performed
Low incidence of deaths in the subgroups at lower risk
Results are limited to patients with characteristics similar to those enrolled in RELAX-AHF (e.g., SBP >125 mmHg, <16 h from presentation)

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.

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