IV infusion serelaxin in patients hospitalized with acute HF did not improve CV mortality at 180 days or worsening HF at 5 days when compared with placebo in the RELAX-AHF-2 trial.
The study, now published in The New England Journal of Medicine, enrolled 6,545 patients (mean age, 73.1 years; 39.6% women; 5% black) hospitalized for acute HF who were assigned to receive a 48-hour IV infusion of serelaxin at 30 µg/kg of body weight per day in addition to standard care (n = 3,274) or placebo (n = 3,271).
At 180 days, the primary endpoint of death from CV causes occurred in 8.7% of the serelaxin group vs. 8.9% of the placebo group (HR = 0.98; 95% CI, 0.83-1.15; P = .77). The second primary endpoint, worsening HF at day 5, occurred in 6.9% of the serelaxin group vs. 7.7% of the placebo group (HR = 0.89; 95% CI, 0.75-1.07; P = .19). On the basis of these findings, the researchers concluded that there is no significant difference in serelaxin use compared with placebo for death from any cause at 180 days or incidence of death from CV causes, as well as other outcomes including rehospitalization for HF or renal failure at 180 days and length of stay.
The data were reported previously at Heart Failure 2017.
“Serelaxin treatment resulted in a significantly greater reduction in blood pressure than placebo, a finding consistent with a pharmacologic effect of serelaxin,” Marco Metra, MD, professor of cardiology at the University of Brescia, Italy, and colleagues wrote in NEJM. “However, serelaxin did not result in lower cardiovascular mortality at 180 days or a smaller percentage of patients with worsening heart failure at 5 days than placebo. The incidence of adverse events was similar in the two groups.”
In other results, mean BP was lower in the serelaxin group compared with the placebo group after 30 minutes of infusion and remained lower for 3 days, which researchers stated was consistent with a pharmacological effect of the therapy.
RELAX-AHF-2 was a multicenter, double-blind, placebo-controlled, event-driven trial designed to assess the effects of serelaxin in patients hospitalized with acute HF. Patients enrolled also had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency and a systolic BP of at least 125 mm Hg.
In a discussion of the study, the researchers noted that “the repeated failure of short-term interventions to improve outcomes in acute heart failure has focused attention on aspects of clinical trial design. The timing of therapy, the imprecision of the diagnosis of acute heart failure and the failure to align the mechanism of action of the drug being evaluated with the patient population that is most likely to benefit from it have been identified as potential problems.” – by Scott Buzby
Disclosures: This study was funded by Novartis. Please see the full study for the other authors’ relevant financial disclosures.