Most patients admitted for acute heart failure have normal or increase blood pressure.
Relaxin is a natural human peptide that affects multiple vascular control pathways,
suggesting potential mechanisms of benefit for such patients. We assessed the dose
response of relaxin's effect on symptom relief, other clinical outcomes, and safety.
In a placebo-controlled, parallel-group, dose-ranging study, 234 patients with acute
heart failure, dyspnoea, congestion on chest radiograph, and increased brain natriuretic
peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency,
and systolic blood pressure greater than 125 mm Hg were recruited from 54 sites in
eight countries and enrolled within 16 h of presentation. Patients were randomly assigned,
in a double-blind manner via a telephone-based interactive voice response system,
to standard care plus 48-h intravenous infusion of placebo (n=62) or relaxin 10 microg/kg
(n=40), 30 microg/kg (n=43), 100 microg/kg (n=39), or 250 microg/kg (n=50) per day.
Several clinical endpoints were explored to assess whether intravenous relaxin should
be pursued in larger studies of acute heart failure, to identify an optimum dose,
and to help to assess endpoint selection and power calculations. Analysis was by modified
intention to treat. This study is registered with ClinicalTrials.gov, number NCT00520806.
In the modified intention-to-treat population, 61 patients were assessed in the placebo
group, 40 in the relaxin 10 microg/kg per day group, 42 in the relaxin 30 microg/kg
per day group, 37 in the relaxin 100 microg/kg per day group, and 49 in the relaxin
250 microg/kg per day group. Dyspnoea improved with relaxin 30 microg/kg compared
with placebo, as assessed by Likert scale (17 of 42 patients [40%] moderately or markedly
improved at 6 h, 12 h, and 24 h vs 14 of 61 [23%]; p=0.044) and visual analogue scale
through day 14 (8214 mm x h [SD 8712] vs 4622 mm x h [9003]; p=0.053). Length of stay
was 10.2 days (SD 6.1) for relaxin-treated patients versus 12.0 days (7.3) for those
given placebo, and days alive out of hospital were 47.9 (10.1) versus 44.2 (14.2).
Cardiovascular death or readmission due to heart or renal failure at day 60 was reduced
with relaxin (2.6% [95% CI 0.4-16.8] vs 17.2% [9.6-29.6]; p=0.053). The number of
serious adverse events was similar between groups.
When given to patients with acute heart failure and normal-to-increased blood pressure,
relaxin was associated with favourable relief of dyspnoea and other clinical outcomes,
with acceptable safety.