Serelaxin Reduces Dyspnea in HF-PEF Patients in First 24 Hours: RELAX-AHF Analysis

May 28, 2013

LISBON, Portugal — A new analysis of the Relaxin for the Treatment of Acute Heart Failure (RELAX-AHF) trial, which stratified patients based on ejection-fraction status, suggests that serelaxin (Novartis Pharmaceuticals) may be more effective in reducing shortness of breath during the first 24 hours in heart-failure patients with preserved ejection fractions (HF-PEF) than in those with reduced ejection fractions (HF-REF).

In contrast, treatment with serelaxin, a novel recombinant form of human relaxin 2, resulted in similar improvements in area-under-the-curve (AUC) from baseline to day 5 on a dyspnea visual analog scale (VAS) in patients with HF-PEF and HF-REF. "There was no interaction between the two groups," lead investigator Dr Gerasimos Filippatos (Athens University Hospital Attikon, Greece) said regarding dyspnea on day five. "The results were similar for those with preserved ejection fraction and those with reduced ejection fraction."

In contrast, while there was only a numerical decrease in dyspnea measured at 24 hours using the Likert scale in the overall trial, Filippatos noted, "there was a better effect in those with left ventricular ejection fractions greater than 50%."

The results of the RELAX-AHF analysis were presented during a late-breaking clinical-trials session here today at the Heart Failure Congress 2013 of the European Society of Cardiology Heart Failure Association.

Limited Treatment Options for HF-PEF

In RELAX-AHF, 26% of the study cohort had preserved ejection fractions, defined as >50%. In terms of patient characteristics, those with preserved and reduced ejection fractions did differ in some ways. For example, those with HF-PEF were older, had slightly higher systolic blood pressure, were more likely to be female, arrived a little later at hospital, were more likely to have hypertension, and were more likely to be treated with an aldosterone antagonist.

As in the overall study population, which showed no improvement in cardiovascular death or hospitalization for heart or renal failure through day 60, there was no improvement in clinical outcomes in patients with HF-PEF or HF-REF. Cardiovascular death and all-cause mortality at day 180 were both significantly reduced by 37% overall, but investigators did not observe a significant interaction based on ejection-fraction status. In addition, there was no significant interaction with regard to changes in biomarkers, such as cardiac cystatin C or N-terminal prohormone of brain natriuretic peptide (NT-proBNP).

On the whole, Filippatos said that the data confirm that the drug is equally effective for the reduction of dyspnea through day 5 in both types of heart-failure patients and is "also equally effective at improving short- and long-term outcomes, including survival, irrespective of the ejection fraction."

Commenting on the study results, Dr Mihai Gheorghiade (Northwestern University Feinberg School of Medicine, Chicago, IL) said that while progress has been made in the treatment of outpatients living with heart failure, the same progress has not been observed among patients hospitalized with heart failure. This is evident by the unacceptably high rates of postdischarge mortality and readmission--rates that haven't changed in the past 10 years. Regarding patients with heart failure, he noted that regardless of their ejection-fraction status, hospitalizations for heart failure affect patients equally, even though the number of patients with HF-PEF is growing.

"What's interesting is that once you admit the patient for heart failure, the ejection fraction is no longer a major prognostic indicator," said Gheorghiade. "The readmission and mortality [rates] are almost equal in patients with preserved and reduced ejection fractions."

RELAX-AHF, in a nutshell

The RELAX-AHF study included 1160 patients with acute heart failure and systolic blood pressure >125 mm Hg randomized to serelaxin (via a 48-hour intravenous infusion within 16 hours of presentation) or placebo. As reported by heartwire , serelaxin resulted in a 19% improvement in AUC from baseline to day 5 on a dyspnea VAS, as well as a moderate--but not statistically significant--improvement in dyspnea at 24 hours measured using a Likert scale.

Days alive out of the hospital at day 60 and cardiovascular death or heart-failure/renal-failure hospitalizations up to day 60--the secondary end points--were not significantly improved with serelaxin. Overall, there was a significant 37% reduction in both risk of all-cause and cardiovascular mortality at six months with serelaxin.

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