Compared with placebo, serelaxin infusion did not lower the incidence of worsening heart failure at 5 days or cardiovascular (CV)-related death at 180 days among patients hospitalized for acute heart failure (AHF), according to study results published in the New England Journal of Medicine.
Serelaxin is a recombinant form of human relaxin-2, which is a vasodilator hormone that contributes to renal and CV adaptations in pregnancy. This multicenter, placebo-controlled, double-blind, event-driven clinical trial (RELAX-AHF-2) enrolled participants hospitalized for AHF who also had dyspnea, mild-to-moderate renal insufficiency, increased plasma concentrations of natriuretic peptides, vascular congestion on chest radiography, and a systolic blood pressure ≥125 mm Hg.
Sixteen hours after presentation, researchers randomly assigned the 6600 participants at a 1:1 ratio to either receive placebo or a 48-hour intravenous infusion of serelaxin at 30 μg/kg of body weight per day in addition to standard care.
A total of 55 participants who took placebo and 40 participants who took serelaxin had to be omitted from the final analysis either because of randomization error or because they were enrolled at a site that was closed because of Good Clinical Practice violations. The primary study endpoints were worsening HF at 5 days and death at 180 days from CV causes.
The intention-to-treat analysis included a total 6545 participants. About one-fifth ( 21.9%) of the serelaxin group (n=717) and 15.7% of the placebo group (n=512) discontinued infusions, with the most common reason being a systolic blood pressure decrease meeting the protocol discontinuation criteria.
Worsening HF at day 5 occurred in 227 (6.9%) serelaxin participants, and 252 (7.7%) placebo participants (hazard ratio 0.89; 95% CI, 0.75-1.07; P =.19).
Death from CV causes at day 180 occurred in 285 (8.7%) serelaxin participants and 290 (8.9%) placebo participants (hazard ratio 0.98; 95% CI, 0.83-1.15; P =.77). The researchers observed no significant between-group differences in length of index hospital stay or in day 180 all-cause death, incidence of CV-related death, or rehospitalization for renal failure or heart failure. The rate of adverse events was similar between groups.
Study investigators concluded, “The RELAX-AHF-2 trial evaluated the effect of serelaxin in patients with [HF]. Serelaxin treatment resulted in a significantly greater reduction in blood pressure than placebo, a finding consistent with a pharmacologic effect of serelaxin. However, serelaxin did not result in lower [CV] mortality at 180 days or a smaller percentage of patients with worsening [HF] at 5 days than placebo. The incidence of adverse events was similar in the two groups.”
Disclosure: This clinical trial was supported by Novartis Pharmaceuticals Corporation. Please see the original reference for a full list of authors’ disclosures.
Metra M, Teerlink JR, Cotter G, et al. Effects of serelaxin in patients with acute heart failure. N Engl J Med. 2019;381(8):716-726.