Serelaxin treatment does not reduce incidence of death in patients with AHF

In the RELAX-AHF trial published in 2013, patients with acute heart failure (AHF) treated with serelaxin, a recombinant form of human relaxin 2, had a reduced incidence of worsening HF and cardiovascular death. However, this trial was not powered to assess effects on mortality. Investigators in the RELAX-AHF-2 trial, which is five times larger than the previous trial, now report that early administration of serelaxin in patients admitted to hospital for AHF did not have a significant effect on cardiovascular mortality.

Relaxin is a pleiotropic hormone with powerful anti-fibrotic and anti-inflammatory properties. Given the vasodilatory effects and possible cardioprotective effects of this hormone, serelaxin was developed as a potential therapy for the treatment of AHF.

The RELAX-AHF-2 study was a multicentre, randomized, event-driven trial designed to test whether serelaxin treatment reduced the incidence of death at 180 days or the incidence of worsening HF in the first 5 days compared with placebo. In total, 3,274 patients assigned to serelaxin treatment and 3,271 assigned to placebo were included in the analysis. At day 180, no significant difference was observed in death from cardiovascular causes between serelaxin-treated and placebo-treated patients (8.7% versus 8.9%; HR 0.98, 95% CI 0.83–1.15, P = 0.77). In addition, at day 5, no significant difference in worsening HF was observed between the two groups (6.9% versus 7.7%; HR 0.89, 95% CI 0.75–1.07, P = 0.19).

To conclude, the results of the RELAX-AHF-2 trial did not replicate the benefit of serelaxin seen in the previous RELAX-AHF trial. “The negative result for the end point of death from cardiovascular causes in the RELAX-AHF-2 trial is … consistent with the conclusion that the result in the RELAX-AHF trial was a chance finding,” explain the investigators.