Serelaxin Effective in Patients with Acute Heart Failure

Los Angeles—Patients with acute heart failure who took serelaxin intravenously for 48 hours had an improvement in dyspnea relief, in-hospital signs and symptoms of acute heart failure, in-hospital worsening of heart failure, and 180-day cardiovascular and all-cause mortality compared with a placebo group, according to a phase 3, prospective, randomized, double-blind, placebo-controlled, parallel-group trial.

The serelaxin group had 45% fewer episodes of worsening heart failure symptoms during hospitalization and spent nearly a full day less in the hospital than those in the placebo group. The drug, a peptide hormone and a recombinant form of the human hormone relaxin-2, had no effect on rehospitalizations, and it was safe with a similar profile to placebo.

John Teerlink, MD, the study’s co-lead author and professor of medicine at the University of California in San Francisco, presented the findings in a late-breaking abstract session at the AHA meeting. Results were also published in Lancet [https://dx.doi.org/10.1016/S0140-6736(12)61855-8].

Novartis, the manufacturer of serelaxin, funded the study.

When introducing the trial, Dr. Teerlink said relaxin is a pregnancy hormone and pregnancy requires “tremendous” improvement in cardiac output and vascular and renal performance. In previous trials, relaxin mediated the adaptations associated with pregnancy and had anti-ischemic, anti-inflammatory, and anti-fibrotic effects.

The authors applied the principles learned in those trials and applied them to this study, which was called RELAX-AHF (Relaxin in Acute Heart Failure). They began with a phase 2 pilot study of 234 patients that found the 30 mcg/kg daily dose of serelaxin led to improvements in dyspnea and other in-hospital benefits as well as potential improvement in cardiovascular and all-cause survival. Dr. Teerlink added the drug was safe and well tolerated. There were no significant adverse events.

Patients were included if they were ≥18 years of age, hospitalized for acute heart failure, received at least 40 mg of furosemide administered intravenously between the time of admission to emergency services and study screening, systolic blood pressure >125 mm Hg, impaired renal function, and weighed <160 kg. Exclusion criteria included treatment with any intravenous therapies, stroke within 60 days, acute coronary syndrome within 45 days, major surgery within 30 days, and presence of acute myocarditis, significant valvular heart disease, and hypertrophic/restrictive/constrictive cardiomyopathy.

The authors randomized patients in a 1:1 ratio to receive 30 mcg/kg of serelaxin or placebo daily administered intravenously for 48 hours. Patients were enrolled between October 2009 and February 2012 at 96 sites in 11 countries. They received the medication within 16 hours of hospitalization. Mean age was approximately 72 years, and most had elevated systolic blood pressure (mean of 142 mmHg).

Through 180 days, there was a significant improvement favoring the serelaxin group in cardiovascular mortality (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.41-0.96; P=.028) as well as in all-cause death (HR, 0.63; 95% CI, 0.43-0.93; P=.02). There were also significant improvements in the signs and symptoms of congestion at day 2.

From baseline through day 5, there was a 19.4% increase in the area under the curve for dyspnea relief in patients who took serelaxin compared with placebo (P=.0075). Dr. Teerlink said that results showed serelaxin improved survival according to the authors’ pre-specified criteria.

There was no significant difference in cardiovascular death or heart failure re-hospitalization through day 60 (HR, 1.02; 95% CI, 0.74-1.41; P=.89). There was a 30% reduction in cardiovascular deaths in the serelaxin group but a 20% increase in re-hospitalizations in patients who took serelaxin, although the differences were not statistically significant, according to the study authors.