• Cardiology Clinical Trials
• Heart Failure

Relaxin, a naturally occurring vasodilator, improves symptoms and lessens the risk of cardiovascular death and heart failure rehospitalization in patients hospitalized with acute heart failure, according to findings from the Preliminary Study of Relaxin in Acute Heart Failure (Pre-RELAX-AHF; NCT00520806).

Relaxin is a peptide hormone that increases in serum concentration in pregnant women to facilitate the hemodynamic adjustments of pregnancy, including increased cardiac output and decreased vascular resistance. The phase 2 Pre-RELAX-AHF trial was designed to evaluate the effects of relaxin in patients with similar physiologic changes due to heart failure. John R. Teerlink, MD, University of California San Francisco, CA, presented results from Pre-RELAX-AHF, which were simultaneously published online in The Lancet.

The trial enrolled 234 patients with acute heart failure characterized by dyspnea and congestion on chest X-ray, normal or elevated systolic blood pressure (>125 mm Hg), impaired renal function (CrCl 30–75 mL/min) and elevated brain natriuretic peptide (BNP). After receiving intravenous furosemide and within 16 hours of presentation, patients were randomly assigned to treatment with intravenous placebo (n=62) or relaxin 10 μg/kg (n=40), 30 μg/kg (n=43), 100 μg/kg (n=39), or 250 μg/kg (n=50) for 48 hours. Pre-RELAX-AHF had no prespecified primary endpoint and assessed clinical outcomes such as relief of dyspnea, inhospital worsening of heart failure, renal impairment and hospital stay, among others.

Relaxin showed a preferential vasodilatory effect, providing a greater blood pressure reduction compared with placebo among patients with baseline systolic blood pressure >140 mm Hg (p=0.04), but not in those with systolic blood pressure ≤140 mm Hg (p=0.73).

Patients in the 30 μg/kg dosing group appeared to benefit the most from relaxin treatment. Compared with placebo, patients in the 30 μg/kg group reported a moderate or marked improvement in dyspnea (Likert scale) at 6, 12, and 24 hours (p=0.044), which was sustained through Day 14 (p=0.053). Relaxin 30 μg/kg also numerically reduced the mean length of hospital stay by nearly 2 days (12.0 vs 10.2 days; p=0.18).

Relaxin improved clinical outcomes following hospital discharge as well. Compared with placebo, relaxin 30 μg/kg reduced the risk of cardiovascular death or rehospitalization due to heart failure or renal failure by 87% at 60 days (HR, 0.13; p=0.053). No patients died because of cardiovascular causes in the Relaxin 30 μg/kg group at 180 days (p<0.05).

Relaxin had a favorable safety profile, with a similar proportion of patients reporting any adverse event in the placebo and relaxin groups. Compared with placebo, relaxin 30 μg/kg was associated with a nonsignificant increase in the incidence of bronchitis (0 vs 2.4%), stroke (1.6% vs 4.8%), renal failure (1.6% vs 2.4%), and hypotension (9.8% vs 11.9%). No cases of severe hypotension were reported in the placebo or relaxin 30 μg/kg groups, though 2 cases (4.1%) were reported in the relaxin 250 μg/kg group. Relaxin 250 μg/kg, but not 30 μg/kg, was associated with a nonsignifcant doubling in the incidence of worsening renal dysfunction (≥0.3 mg/dL increase in serum creatinine) compared with placebo (15% vs 7%, p=0.19).

Based on these findings, Dr. Teerlink and colleagues have chosen the 30 μg/kg dose for evaluation in the upcoming international phase 3 trial of relaxin in acute heart failure (RELAX-AHF-1).

• © 2009 MD Conference Express