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Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure.

Publication ,  Journal Article
Beldhuis, IE; Ter Maaten, JM; Figarska, SM; Damman, K; Pang, PS; Greenberg, B; Davison, BA; Cotter, G; Severin, T; Gimpelewicz, C; Felker, GM ...
Published in: Clin Res Cardiol
July 2023

BACKGROUND: We aimed to study whether improvement in renal function by serelaxin in patients who were hospitalized for acute heart failure (HF) might explain any potential effect on clinical outcomes. METHODS: We included 6318 patients from the RELAXin in AHF-2 (RELAX-AHF2) study. Improvement in renal function was defined as a decrease in serum creatinine of ≥ 0.3 mg/dL and ≥ 25%, or increase in estimated glomerular filtration rate of ≥ 25% between baseline and day 2. Worsening renal function (WRF) was defined as the reverse. We performed causal mediation analyses regarding 180-day all-cause mortality (ACM), cardiovascular death (CVD), and hospitalization for HF/renal failure. RESULTS: Improvement in renal function was more frequently observed with serelaxin when compared with placebo [OR 1.88 (95% CI 1.64-2.15, p < 0.0001)], but was not associated with subsequent clinical outcomes. WRF occurred less frequent with serelaxin [OR 0.70 (95% CI 0.60-0.83, p < 0.0001)] and was associated with increased risk of ACM, worsening HF and the composite of CVD and HF or renal failure hospitalization. Improvement in renal function did not mediate the treatment effect of serelaxin [CVD HR 1.01 (0.99-1.04), ACM HR 1.01 (0.99-1.03), HF/renal failure hospitalization HR 0.99 (0.97-1.00)]. CONCLUSIONS: Despite the significant improvement in renal function by serelaxin in patients with acute HF, the potential beneficial treatment effect was not mediated by improvement in renal function. These data suggest that improvement in renal function might not be a suitable surrogate marker for potential treatment efficacy in future studies with novel relaxin agents in acute HF. Central illustration. Conceptual model explaining mediation analysis; treatment efficacy of heart failure therapies mediated by renal function.

Duke Scholars

Published In

Clin Res Cardiol

DOI

EISSN

1861-0692

Publication Date

July 2023

Volume

112

Issue

7

Start / End Page

901 / 910

Location

Germany

Related Subject Headings

  • Vasodilator Agents
  • Treatment Outcome
  • Renal Insufficiency
  • Relaxin
  • Recombinant Proteins
  • Kidney
  • Humans
  • Heart Failure
  • Cardiovascular System & Hematology
  • Acute Disease
 

Citation

APA
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MLA
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Beldhuis, I. E., Ter Maaten, J. M., Figarska, S. M., Damman, K., Pang, P. S., Greenberg, B., … Voors, A. A. (2023). Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure. Clin Res Cardiol, 112(7), 901–910. https://doi.org/10.1007/s00392-022-02144-6
Beldhuis, I. E., J. M. Ter Maaten, S. M. Figarska, K. Damman, P. S. Pang, B. Greenberg, B. A. Davison, et al. “Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure.Clin Res Cardiol 112, no. 7 (July 2023): 901–10. https://doi.org/10.1007/s00392-022-02144-6.
Beldhuis IE, Ter Maaten JM, Figarska SM, Damman K, Pang PS, Greenberg B, et al. Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure. Clin Res Cardiol. 2023 Jul;112(7):901–10.
Beldhuis, I. E., et al. “Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure.Clin Res Cardiol, vol. 112, no. 7, July 2023, pp. 901–10. Pubmed, doi:10.1007/s00392-022-02144-6.
Beldhuis IE, Ter Maaten JM, Figarska SM, Damman K, Pang PS, Greenberg B, Davison BA, Cotter G, Severin T, Gimpelewicz C, Felker GM, Filippatos G, Teerlink JR, Metra M, Voors AA. Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure. Clin Res Cardiol. 2023 Jul;112(7):901–910.
Journal cover image

Published In

Clin Res Cardiol

DOI

EISSN

1861-0692

Publication Date

July 2023

Volume

112

Issue

7

Start / End Page

901 / 910

Location

Germany

Related Subject Headings

  • Vasodilator Agents
  • Treatment Outcome
  • Renal Insufficiency
  • Relaxin
  • Recombinant Proteins
  • Kidney
  • Humans
  • Heart Failure
  • Cardiovascular System & Hematology
  • Acute Disease