Serelaxin in acute HF: study calls reported survival benefit into question

  • Metra M & al.
  • N Engl J Med
  • 22 Aug 2019

  • International Clinical Digest
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Takeaway

  • In this third trial to address whether 48-hour serelaxin infusion is linked to cardiovascular mortality reductions in acute heart failure (HF), the therapy showed no such benefit.
  • The treatment also showed no benefit for 5-day HF worsening or hospital-related measures. 

Why this matters

  • In an initial trial, this vasodilator was associated with a “dramatic reduction in mortality,” but a second trial planned to assess this endpoint found no such benefit. 
  • Editorial: this third trial confirms this lack of effect.

Key results

  • For serelaxin vs placebo, 180-day cardiovascular mortality rates were, respectively, 8.7% vs 8.9%:
    • HR, 0.98 (95% CI, 0.83-1.15; P=.77).
  • Day-5 HF worsening rates for serelaxin vs placebo were, respectively, 6.9% vs 7.7%:
    • HR, 0.89 (95% CI, 0.75-1.07; P=.19).
  • All-cause death (drug vs placebo: 11.2% vs 11.9%) rehospitalization for HF, renal failure (24.3% vs 24.9%) at 180 days also did not differ between groups, nor did the length of the initial hospital stay (6.8 vs 6.9 days).
  • Adverse event rates were similar between groups (drug vs placebo: 53.1% vs 52.1%).

Study design

  • Multicentre, double-blind, placebo-controlled trial with 6600 patients with acute HF randomly allocated to serelaxin infusion (n=3298) or placebo (n=3302).
  • Funding: Novartis Pharma.

Limitations

  • Protocol to prevent drug-induced hypotension led to smaller number of patients receiving serelaxin for the full 48 hours.