Effects of serelaxin in acute heart failure patients with renal impairment: results from RELAX-AHF

Clin Res Cardiol. 2016 Sep;105(9):727-37. doi: 10.1007/s00392-016-0979-8. Epub 2016 Mar 26.

Abstract

Background: Serelaxin showed beneficial effects on clinical outcome and trajectories of renal markers in patients with acute heart failure. We aimed to study the interaction between renal function and the treatment effect of serelaxin.

Methods: In the current post hoc analysis of the RELAX-AHF trial, we included all patients with available estimated glomerular filtration rate (eGFR) at baseline (n = 1132). Renal impairment was defined as an eGFR <60 ml/min/1.73 m(2) estimated by creatinine.

Results: 817 (72.2 %) patients had a baseline eGFR <60 ml/min/1.73 m(2). In placebo-treated patients, baseline renal impairment was related to a higher 180 day cardiovascular (HR 3.12, 95 % CI 1.33-7.30) and all-cause mortality (HR 2.81, 95 % CI 1.34-5.89). However, in serelaxin-treated patients, the risk of cardiovascular and all-cause mortality was less pronounced (HR 1.19, 95 % CI 0.54 -2.64; p for interaction = 0.106, and HR 1.15 95 % CI 0.56-2.34 respectively; p for interaction = 0.088). In patients with renal impairment, treatment with serelaxin resulted in a more pronounced all-cause mortality reduction (HR 0.53, 95 % CI 0.34-0.83), compared with patients without renal impairment (HR 1.30, 95 % CI 0.51-3.29).

Conclusion: Renal dysfunction was associated with higher cardiovascular and all-cause mortality in placebo-treated patients, but not in serelaxin-treated patients. The observed reduction in (cardiovascular) mortality in RELAX-AHF was more pronounced in patients with renal dysfunction. These observations need to be confirmed in the ongoing RELAX-AHF-2 trial.

Keywords: Acute heart failure; Number needed to treat; Renal function; Renal impairment; Serelaxin.

MeSH terms

  • Acute Disease
  • Aged
  • Aged, 80 and over
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / therapeutic use*
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Humans
  • Kaplan-Meier Estimate
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Kidney Diseases / complications
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / mortality
  • Kidney Diseases / physiopathology
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Relaxin / adverse effects
  • Relaxin / therapeutic use*
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Cardiovascular Agents
  • Recombinant Proteins
  • serelaxin protein, human
  • Relaxin