Serelaxin in Acute Heart Failure Patients With Preserved Left Ventricular Ejection Fraction: Results From the RELAX-AHF Trial

Study Questions:

What are the effects of serelaxin according to ejection fraction (EF) in acute heart failure (AHF)?

Methods:

The study cohort in the RELAX-AHF trial was comprised of 1,161 AHF patients who were randomized to 48-hour serelaxin (30 mg/kg/day) or placebo within 16 hours from presentation. In this post-hoc study, authors compared the effects of serelaxin on efficacy endpoints, safety endpoints, and biomarkers of organ damage between preserved (≥50%, HFpEF) and reduced (<50%, HFrEF) EF patients.

Results:

Twenty-six percent of the study cohort had HFpEF. The study authors found that the dyspnea relief (using the visual analogue scale-area under the curve through day 5) by serelaxin was similar in both HFpEF vs. HFrEF groups [mean change, 461 (2,195, 1,117) vs. 397 (10, 783) mm h, p = 0.87], but had possibly different effects on the proportion of patients with moderately or markedly dyspnea improvement by Likert scale at 6, 12, and 24 hours [odds ratio for favorable response, 1.70 (0.98, 2.95) vs. 0.85 (0.62, 1.15), interaction p = 0.030]. They found no differences 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. The safety and changes in biomarkers (high-sensitivity troponin T, cystatin-C, and alanine/aspartate aminotransferases) were similar in both groups.

Conclusions:

The study authors concluded that serelaxin was well tolerated and effective in relieving dyspnea in AHF patients with HFpEF when compared with those with HFrEF, and had a similar effect on short- and long-term outcome, including survival improvement.

Perspective:

Serelaxin is a recombinant form of human relaxin-2. In the RELAX-AHF study (Lancet 2013;381:29-39), a 48-hour infusion of serelaxin in AHF patients improved shortness of breath and other symptoms and signs of congestion, and it also reduced worsening in early AHF and length of hospital stay. Serelaxin was well tolerated and provided a significant 37% reduction in 180-day cardiovascular and all-cause mortality. In addition, the drug induced a short-term favorable effect on biomarkers of cardiac, kidney, and liver injury, an effect that may be associated with increased survival. This report shows that there was a significant proportion of HFpEF patients in the study cohort unlike other studies of AHF, suggesting that this drug may have a beneficial effect in both HFrEF and HFpEF patients. Although, the RELAX-AHF study was not designed or powered to assess mortality and this report was a post-hoc analysis, the findings of this study should prompt a randomized clinical trial to determine the efficacy of this promising drug in AHF.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Odds Ratio, Ventricular Function, Left, Troponin T, Dyspnea, Renal Insufficiency, Biological Markers, Heart Failure, Liver, Stroke Volume, Kidney, Relaxin, Cystatin C


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