Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial.

Abstract

Serelaxin is effective in relieving dyspnoea and improving multiple outcomes in acute heart failure (AHF). Many AHF patients have preserved ejection fraction (HFpEF). Given the lack of evidence-based therapies in this population, we evaluated the effects of serelaxin according to EF in RELAX-AHF trial. RELAX-AHF randomized 1161 AHF patients to 48-h serelaxin (30 μg/kg/day) or placebo within 16 h from presentation. We compared the effects of serelaxin on efficacy endpoints, safety endpoints, and biomarkers of organ damage between preserved (≥50%) and reduced (<50%, HFrEF) EF. HFpEF was present in 26% of patients. Serelaxin induced a similar dyspnoea relief in HFpEF vs. HFrEF patients by visual analogue scale-area under the curve (VAS-AUC) through Day 5 [mean change, 461 (-195, 1117) vs. 397 (10, 783) mm h, P = 0.87], but had possibly different effects on the proportion of patients with moderately or markedly dyspnoea improvement by Likert scale at 6, 12, and 24 h [odds ratio for favourable response, 1.70 (0.98, 2.95) vs. 0.85 (0.62, 1.15), interaction P = 0.030]. No differences were encountered in the effect of serelaxin on short- or long-term outcome between HFpEF and HFrEF patients including cardiovascular death or hospitalization for heart/renal failure through Day 60, cardiovascular death through Day 180, and all-cause death through Day 180. Similar safety and changes in biomarkers (high-sensitivity troponin T, cystatin-C, and alanine/aspartate aminotransferases) were found in both groups. In AHF patients with HFpEF compared with those with HFrEF, serelaxin was well tolerated and effective in relieving dyspnoea and had a similar effect on short- and long-term outcome, including survival improvement.