Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation: The PARADIGM-HF Trial

Scott D. Solomon, Brian Claggett, Milton Packer, Akshay Desai, Michael R. Zile, Karl Swedberg, Jean Rouleau, Victor Shi, Martin Lefkowitz, John J V McMurray

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Objectives This study assessed whether the benefit of sacubtril/valsartan therapy varied with clinical stability. Background Despite the benefit of sacubitril/valsartan therapy shown in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, it has been suggested that switching from an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker should be delayed until occurrence of clinical decompensation. Methods Outcomes were compared among patients who had prior hospitalization within 3 months of screening (n = 1,611 [19%]), between 3 and 6 months (n = 1,009 [12%]), between 6 and 12 months (n = 886 [11%]), >12 months (n = 1,746 [21%]), or who had never been hospitalized (n = 3,125 [37%]). Results Twenty percent of patients without prior HF hospitalization experienced a primary endpoint of cardiovascular death or heart failure (HF) hospitalization during the course of the trial. Despite the increased risk associated with more recent hospitalization, the efficacy of sacubitril/valsartan therapy did not differ from that of enalapril according to the occurrence of or time from hospitalization for HF before screening, with respect to the primary endpoint or with respect to cardiovascular or all-cause mortality. Conclusions Patients with recent HF decompensation requiring hospitalization were more likely to experience cardiovascular death or HF hospitalization than those who had never been hospitalized. Patients who were clinically stable, as shown by a remote HF hospitalization (>3 months prior to screening) or by lack of any prior HF hospitalization, were as likely to benefit from sacubitril/valsartan therapy as more recently hospitalized patients. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255)

Original languageEnglish (US)
Pages (from-to)816-822
Number of pages7
JournalJACC: Heart Failure
Volume4
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

Heart Failure
Hospitalization
Valsartan
Mortality
LCZ 696
Morbidity
Enalapril
Angiotensin Receptor Antagonists
Therapeutics
Angiotensin-Converting Enzyme Inhibitors

Keywords

  • heart failure
  • neprilysin inhibition
  • renin angiotensin system

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Solomon, S. D., Claggett, B., Packer, M., Desai, A., Zile, M. R., Swedberg, K., ... McMurray, J. J. V. (2016). Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation: The PARADIGM-HF Trial. JACC: Heart Failure, 4(10), 816-822. https://doi.org/10.1016/j.jchf.2016.05.002

Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation : The PARADIGM-HF Trial. / Solomon, Scott D.; Claggett, Brian; Packer, Milton; Desai, Akshay; Zile, Michael R.; Swedberg, Karl; Rouleau, Jean; Shi, Victor; Lefkowitz, Martin; McMurray, John J V.

In: JACC: Heart Failure, Vol. 4, No. 10, 01.10.2016, p. 816-822.

Research output: Contribution to journalArticle

Solomon, SD, Claggett, B, Packer, M, Desai, A, Zile, MR, Swedberg, K, Rouleau, J, Shi, V, Lefkowitz, M & McMurray, JJV 2016, 'Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation: The PARADIGM-HF Trial', JACC: Heart Failure, vol. 4, no. 10, pp. 816-822. https://doi.org/10.1016/j.jchf.2016.05.002
Solomon, Scott D. ; Claggett, Brian ; Packer, Milton ; Desai, Akshay ; Zile, Michael R. ; Swedberg, Karl ; Rouleau, Jean ; Shi, Victor ; Lefkowitz, Martin ; McMurray, John J V. / Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation : The PARADIGM-HF Trial. In: JACC: Heart Failure. 2016 ; Vol. 4, No. 10. pp. 816-822.
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abstract = "Objectives This study assessed whether the benefit of sacubtril/valsartan therapy varied with clinical stability. Background Despite the benefit of sacubitril/valsartan therapy shown in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, it has been suggested that switching from an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker should be delayed until occurrence of clinical decompensation. Methods Outcomes were compared among patients who had prior hospitalization within 3 months of screening (n = 1,611 [19{\%}]), between 3 and 6 months (n = 1,009 [12{\%}]), between 6 and 12 months (n = 886 [11{\%}]), >12 months (n = 1,746 [21{\%}]), or who had never been hospitalized (n = 3,125 [37{\%}]). Results Twenty percent of patients without prior HF hospitalization experienced a primary endpoint of cardiovascular death or heart failure (HF) hospitalization during the course of the trial. Despite the increased risk associated with more recent hospitalization, the efficacy of sacubitril/valsartan therapy did not differ from that of enalapril according to the occurrence of or time from hospitalization for HF before screening, with respect to the primary endpoint or with respect to cardiovascular or all-cause mortality. Conclusions Patients with recent HF decompensation requiring hospitalization were more likely to experience cardiovascular death or HF hospitalization than those who had never been hospitalized. Patients who were clinically stable, as shown by a remote HF hospitalization (>3 months prior to screening) or by lack of any prior HF hospitalization, were as likely to benefit from sacubitril/valsartan therapy as more recently hospitalized patients. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255)",
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