Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF risk scores: an analysis of mortality and morbidity in PARADIGM-HF

Joanne Simpson, Pardeep S. Jhund, Jose Silva Cardoso, Felipe Martinez, Arend Mosterd, Felix Ramires, Adel R. Rizkala, Michele Senni, Iain Squire, Jianjian Gong, Martin P. Lefkowitz, Victor C. Shi, Akshay S. Desai, Jean L. Rouleau, Karl Swedberg, Michael R. Zile, John J V McMurray, Milton Packer, Scott D. Solomon

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure.

OBJECTIVES: The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum.

METHODS: This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696.

RESULTS: The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6% increased risk for the primary endpoint (p <0.001) and a 7% increased risk for cardiovascular death (p <0.001). The benefit of LCZ696 over enalapril for the primary endpoint was similar across the spectrum of risk (p = 0.159). Treating 100 patients for 2 years with LCZ696 instead of enalapril led to 7 fewer patients in the highest quintile of risk experiencing primary outcomes, compared with 3 in the lowest quintile. Analyses using the EMPHASIS-HF risk score gave similar findings.

CONCLUSIONS: Although most PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696's benefit was consistent across the spectrum of risk. (PARADIGM-HF trial [Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure]; NCT01035255).

Original languageEnglish (US)
Pages (from-to)2059-2071
Number of pages13
JournalJournal of the American College of Cardiology
Volume66
Issue number19
DOIs
StatePublished - Nov 10 2015

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Enalapril
Meta-Analysis
Hospitalization
Heart Failure
Morbidity
Survival
Mortality
eplerenone
LCZ 696

Keywords

  • angiotensin receptor neprilysin inhibitor
  • prognostic model
  • risk score
  • survival

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF risk scores : an analysis of mortality and morbidity in PARADIGM-HF. / Simpson, Joanne; Jhund, Pardeep S.; Silva Cardoso, Jose; Martinez, Felipe; Mosterd, Arend; Ramires, Felix; Rizkala, Adel R.; Senni, Michele; Squire, Iain; Gong, Jianjian; Lefkowitz, Martin P.; Shi, Victor C.; Desai, Akshay S.; Rouleau, Jean L.; Swedberg, Karl; Zile, Michael R.; McMurray, John J V; Packer, Milton; Solomon, Scott D.

In: Journal of the American College of Cardiology, Vol. 66, No. 19, 10.11.2015, p. 2059-2071.

Research output: Contribution to journalArticle

Simpson, J, Jhund, PS, Silva Cardoso, J, Martinez, F, Mosterd, A, Ramires, F, Rizkala, AR, Senni, M, Squire, I, Gong, J, Lefkowitz, MP, Shi, VC, Desai, AS, Rouleau, JL, Swedberg, K, Zile, MR, McMurray, JJV, Packer, M & Solomon, SD 2015, 'Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF risk scores: an analysis of mortality and morbidity in PARADIGM-HF', Journal of the American College of Cardiology, vol. 66, no. 19, pp. 2059-2071. https://doi.org/10.1016/j.jacc.2015.08.878
Simpson, Joanne ; Jhund, Pardeep S. ; Silva Cardoso, Jose ; Martinez, Felipe ; Mosterd, Arend ; Ramires, Felix ; Rizkala, Adel R. ; Senni, Michele ; Squire, Iain ; Gong, Jianjian ; Lefkowitz, Martin P. ; Shi, Victor C. ; Desai, Akshay S. ; Rouleau, Jean L. ; Swedberg, Karl ; Zile, Michael R. ; McMurray, John J V ; Packer, Milton ; Solomon, Scott D. / Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF risk scores : an analysis of mortality and morbidity in PARADIGM-HF. In: Journal of the American College of Cardiology. 2015 ; Vol. 66, No. 19. pp. 2059-2071.
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abstract = "BACKGROUND: Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure.OBJECTIVES: The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum.METHODS: This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696.RESULTS: The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6{\%} increased risk for the primary endpoint (p <0.001) and a 7{\%} increased risk for cardiovascular death (p <0.001). The benefit of LCZ696 over enalapril for the primary endpoint was similar across the spectrum of risk (p = 0.159). Treating 100 patients for 2 years with LCZ696 instead of enalapril led to 7 fewer patients in the highest quintile of risk experiencing primary outcomes, compared with 3 in the lowest quintile. Analyses using the EMPHASIS-HF risk score gave similar findings.CONCLUSIONS: Although most PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696's benefit was consistent across the spectrum of risk. (PARADIGM-HF trial [Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure]; NCT01035255).",
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author = "Joanne Simpson and Jhund, {Pardeep S.} and {Silva Cardoso}, Jose and Felipe Martinez and Arend Mosterd and Felix Ramires and Rizkala, {Adel R.} and Michele Senni and Iain Squire and Jianjian Gong and Lefkowitz, {Martin P.} and Shi, {Victor C.} and Desai, {Akshay S.} and Rouleau, {Jean L.} and Karl Swedberg and Zile, {Michael R.} and McMurray, {John J V} and Milton Packer and Solomon, {Scott D.}",
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TY - JOUR

T1 - Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF risk scores

T2 - an analysis of mortality and morbidity in PARADIGM-HF

AU - Simpson, Joanne

AU - Jhund, Pardeep S.

AU - Silva Cardoso, Jose

AU - Martinez, Felipe

AU - Mosterd, Arend

AU - Ramires, Felix

AU - Rizkala, Adel R.

AU - Senni, Michele

AU - Squire, Iain

AU - Gong, Jianjian

AU - Lefkowitz, Martin P.

AU - Shi, Victor C.

AU - Desai, Akshay S.

AU - Rouleau, Jean L.

AU - Swedberg, Karl

AU - Zile, Michael R.

AU - McMurray, John J V

AU - Packer, Milton

AU - Solomon, Scott D.

PY - 2015/11/10

Y1 - 2015/11/10

N2 - BACKGROUND: Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure.OBJECTIVES: The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum.METHODS: This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696.RESULTS: The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6% increased risk for the primary endpoint (p <0.001) and a 7% increased risk for cardiovascular death (p <0.001). The benefit of LCZ696 over enalapril for the primary endpoint was similar across the spectrum of risk (p = 0.159). Treating 100 patients for 2 years with LCZ696 instead of enalapril led to 7 fewer patients in the highest quintile of risk experiencing primary outcomes, compared with 3 in the lowest quintile. Analyses using the EMPHASIS-HF risk score gave similar findings.CONCLUSIONS: Although most PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696's benefit was consistent across the spectrum of risk. (PARADIGM-HF trial [Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure]; NCT01035255).

AB - BACKGROUND: Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure.OBJECTIVES: The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum.METHODS: This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696.RESULTS: The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6% increased risk for the primary endpoint (p <0.001) and a 7% increased risk for cardiovascular death (p <0.001). The benefit of LCZ696 over enalapril for the primary endpoint was similar across the spectrum of risk (p = 0.159). Treating 100 patients for 2 years with LCZ696 instead of enalapril led to 7 fewer patients in the highest quintile of risk experiencing primary outcomes, compared with 3 in the lowest quintile. Analyses using the EMPHASIS-HF risk score gave similar findings.CONCLUSIONS: Although most PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696's benefit was consistent across the spectrum of risk. (PARADIGM-HF trial [Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure]; NCT01035255).

KW - angiotensin receptor neprilysin inhibitor

KW - prognostic model

KW - risk score

KW - survival

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