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

Licette C Y Liu, Adriaan A. Voors, John R. Teerlink, Gad Cotter, Beth A. Davison, G. Michael Felker, Gerasimos Filippatos, Yakuan Chen, Barry H. Greenberg, Piotr Ponikowski, Peter Pang, Margaret F. Prescott, Tsushung A. Hua, Thomas M. Severin, Marco Metra

Research output: Contribution to journalArticle

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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 2 estimated by creatinine. Results: 817 (72.2 %) patients had a baseline eGFR 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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalClinical Research in Cardiology
DOIs
StateAccepted/In press - Mar 26 2016

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Heart Failure
Kidney
Glomerular Filtration Rate
Mortality
Placebos
Creatinine
Therapeutics

Keywords

  • Acute heart failure
  • Number needed to treat
  • Renal function
  • Renal impairment
  • Serelaxin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Liu, L. C. Y., Voors, A. A., Teerlink, J. R., Cotter, G., Davison, B. A., Felker, G. M., ... Metra, M. (Accepted/In press). Effects of serelaxin in acute heart failure patients with renal impairment: results from RELAX-AHF. Clinical Research in Cardiology, 1-11. https://doi.org/10.1007/s00392-016-0979-8

Effects of serelaxin in acute heart failure patients with renal impairment : results from RELAX-AHF. / Liu, Licette C Y; Voors, Adriaan A.; Teerlink, John R.; Cotter, Gad; Davison, Beth A.; Felker, G. Michael; Filippatos, Gerasimos; Chen, Yakuan; Greenberg, Barry H.; Ponikowski, Piotr; Pang, Peter; Prescott, Margaret F.; Hua, Tsushung A.; Severin, Thomas M.; Metra, Marco.

In: Clinical Research in Cardiology, 26.03.2016, p. 1-11.

Research output: Contribution to journalArticle

Liu, LCY, Voors, AA, Teerlink, JR, Cotter, G, Davison, BA, Felker, GM, Filippatos, G, Chen, Y, Greenberg, BH, Ponikowski, P, Pang, P, Prescott, MF, Hua, TA, Severin, TM & Metra, M 2016, 'Effects of serelaxin in acute heart failure patients with renal impairment: results from RELAX-AHF', Clinical Research in Cardiology, pp. 1-11. https://doi.org/10.1007/s00392-016-0979-8
Liu, Licette C Y ; Voors, Adriaan A. ; Teerlink, John R. ; Cotter, Gad ; Davison, Beth A. ; Felker, G. Michael ; Filippatos, Gerasimos ; Chen, Yakuan ; Greenberg, Barry H. ; Ponikowski, Piotr ; Pang, Peter ; Prescott, Margaret F. ; Hua, Tsushung A. ; Severin, Thomas M. ; Metra, Marco. / Effects of serelaxin in acute heart failure patients with renal impairment : results from RELAX-AHF. In: Clinical Research in Cardiology. 2016 ; pp. 1-11.
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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 2 estimated by creatinine. Results: 817 (72.2 {\%}) patients had a baseline eGFR 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.",
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T2 - results from RELAX-AHF

AU - Liu, Licette C Y

AU - Voors, Adriaan A.

AU - Teerlink, John R.

AU - Cotter, Gad

AU - Davison, Beth A.

AU - Felker, G. Michael

AU - Filippatos, Gerasimos

AU - Chen, Yakuan

AU - Greenberg, Barry H.

AU - Ponikowski, Piotr

AU - Pang, Peter

AU - Prescott, Margaret F.

AU - Hua, Tsushung A.

AU - Severin, Thomas M.

AU - Metra, Marco

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N2 - 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 2 estimated by creatinine. Results: 817 (72.2 %) patients had a baseline eGFR 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.

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KW - Number needed to treat

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KW - Serelaxin

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