Effects of sacubitril/valsartan on physical and social activity limitations in patients with heart failure, A secondary analysis of the PARADIGM-HF trial

Alvin Chandra, Eldrin F. Lewis, Brian L. Claggett, Akshay S. Desai, Milton Packer, Michael R. Zile, Karl Swedberg, Jean L. Rouleau, Victor C. Shi, Martin P. Lefkowitz, Tzvetana Katova, John J.V. McMurray, Scott D. Solomon

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

IMPORTANCE Health-related quality of life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities. In the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril/valsartan improved overall HRQL compared with enalapril, as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ). OBJECTIVE To examine the effects of sacubitril/valsartan on physical and social activities. DESIGN, SETTING, AND PARTICIPANTS The PARADIGM-HF trialwas a randomized, double-blind, active treatment-controlled clinical trial performed from December 8, 2009, to March 31, 2014, in 8399 patients with New York Heart Association class II to IV disease and a left ventricular ejection fraction of 40% or less at 1043 centers in 38 countries. Data analysis was performed from August 1, 2017, to December 25, 2017. INTERVENTIONS Sacubitril/valsartan, 200mg twice daily, or enalapril, 10mg twice daily. MAIN OUTCOMES AND MEASURES Patients completed HRQL assessments using the KCCQ at randomization, 4-month, 8-month, and annual visits. The effect of sacubitril/valsartan on components of the physical and social limitation sections of the KCCQ at 8 months and longitudinally and related biomarkers and clinical outcomes were studied. RESULTS At baseline, 7618 of 8399 patients (90.7%) (mean [SD] age, 64 [11] years; 5987 [78.6%] male and 1631 [21.4%] female) completed the initial KCCQ assessment. Patients reported the greatest limitations at baseline in jogging and sexual relationships. Patients receiving sacubitril/valsartan had significantly better adjusted change scores in most physical and social activities at 8 months and during 36 months compared with those receiving enalapril. The largest improvement over enalapril was in household chores (adjusted change score difference, 2.35; 95%CI, 1.19-3.50; P < .001) and sexual relationships (adjusted change score difference, 2.72; 95%CI, 0.97-4.46; P = .002); both persisted through 36 months (overall change score difference, 1.69 [95%CI, 0.78-2.60], P < .001; and 2.36 [95%CI, 1.01-3.71], P = .001, respectively). CONCLUSIONS AND RELEVANCE In patients with heart failure with reduced ejection fraction, sacubitril/valsartan significantly improved nearly all KCCQ physical and social activities compared with enalapril, with the largest responses in household chores and sexual relationships. In addition to reduced likelihood of cardiovascular death, all-cause mortality, and heart failure hospitalization, sacubitril/valsartan may improve limitations in common activities in these patients.

Original languageEnglish (US)
Pages (from-to)498-505
Number of pages8
JournalJAMA Cardiology
Volume3
Issue number6
DOIs
StatePublished - Jun 2018
Externally publishedYes

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Heart Failure
Exercise
Enalapril
Cardiomyopathies
Quality of Life
Jogging
LCZ 696
Mortality
Controlled Clinical Trials
Random Allocation
Angiotensin-Converting Enzyme Inhibitors
Stroke Volume
Cause of Death
Hospitalization
Chronic Disease
Biomarkers
Surveys and Questionnaires
Morbidity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effects of sacubitril/valsartan on physical and social activity limitations in patients with heart failure, A secondary analysis of the PARADIGM-HF trial. / Chandra, Alvin; Lewis, Eldrin F.; Claggett, Brian L.; Desai, Akshay S.; Packer, Milton; Zile, Michael R.; Swedberg, Karl; Rouleau, Jean L.; Shi, Victor C.; Lefkowitz, Martin P.; Katova, Tzvetana; McMurray, John J.V.; Solomon, Scott D.

In: JAMA Cardiology, Vol. 3, No. 6, 06.2018, p. 498-505.

Research output: Contribution to journalArticle

Chandra, A, Lewis, EF, Claggett, BL, Desai, AS, Packer, M, Zile, MR, Swedberg, K, Rouleau, JL, Shi, VC, Lefkowitz, MP, Katova, T, McMurray, JJV & Solomon, SD 2018, 'Effects of sacubitril/valsartan on physical and social activity limitations in patients with heart failure, A secondary analysis of the PARADIGM-HF trial', JAMA Cardiology, vol. 3, no. 6, pp. 498-505. https://doi.org/10.1001/jamacardio.2018.0398
Chandra, Alvin ; Lewis, Eldrin F. ; Claggett, Brian L. ; Desai, Akshay S. ; Packer, Milton ; Zile, Michael R. ; Swedberg, Karl ; Rouleau, Jean L. ; Shi, Victor C. ; Lefkowitz, Martin P. ; Katova, Tzvetana ; McMurray, John J.V. ; Solomon, Scott D. / Effects of sacubitril/valsartan on physical and social activity limitations in patients with heart failure, A secondary analysis of the PARADIGM-HF trial. In: JAMA Cardiology. 2018 ; Vol. 3, No. 6. pp. 498-505.
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abstract = "IMPORTANCE Health-related quality of life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities. In the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril/valsartan improved overall HRQL compared with enalapril, as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ). OBJECTIVE To examine the effects of sacubitril/valsartan on physical and social activities. DESIGN, SETTING, AND PARTICIPANTS The PARADIGM-HF trialwas a randomized, double-blind, active treatment-controlled clinical trial performed from December 8, 2009, to March 31, 2014, in 8399 patients with New York Heart Association class II to IV disease and a left ventricular ejection fraction of 40{\%} or less at 1043 centers in 38 countries. Data analysis was performed from August 1, 2017, to December 25, 2017. INTERVENTIONS Sacubitril/valsartan, 200mg twice daily, or enalapril, 10mg twice daily. MAIN OUTCOMES AND MEASURES Patients completed HRQL assessments using the KCCQ at randomization, 4-month, 8-month, and annual visits. The effect of sacubitril/valsartan on components of the physical and social limitation sections of the KCCQ at 8 months and longitudinally and related biomarkers and clinical outcomes were studied. RESULTS At baseline, 7618 of 8399 patients (90.7{\%}) (mean [SD] age, 64 [11] years; 5987 [78.6{\%}] male and 1631 [21.4{\%}] female) completed the initial KCCQ assessment. Patients reported the greatest limitations at baseline in jogging and sexual relationships. Patients receiving sacubitril/valsartan had significantly better adjusted change scores in most physical and social activities at 8 months and during 36 months compared with those receiving enalapril. The largest improvement over enalapril was in household chores (adjusted change score difference, 2.35; 95{\%}CI, 1.19-3.50; P < .001) and sexual relationships (adjusted change score difference, 2.72; 95{\%}CI, 0.97-4.46; P = .002); both persisted through 36 months (overall change score difference, 1.69 [95{\%}CI, 0.78-2.60], P < .001; and 2.36 [95{\%}CI, 1.01-3.71], P = .001, respectively). CONCLUSIONS AND RELEVANCE In patients with heart failure with reduced ejection fraction, sacubitril/valsartan significantly improved nearly all KCCQ physical and social activities compared with enalapril, with the largest responses in household chores and sexual relationships. In addition to reduced likelihood of cardiovascular death, all-cause mortality, and heart failure hospitalization, sacubitril/valsartan may improve limitations in common activities in these patients.",
author = "Alvin Chandra and Lewis, {Eldrin F.} and Claggett, {Brian L.} and Desai, {Akshay S.} and Milton Packer and Zile, {Michael R.} and Karl Swedberg and Rouleau, {Jean L.} and Shi, {Victor C.} and Lefkowitz, {Martin P.} and Tzvetana Katova and McMurray, {John J.V.} and Solomon, {Scott D.}",
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TY - JOUR

T1 - Effects of sacubitril/valsartan on physical and social activity limitations in patients with heart failure, A secondary analysis of the PARADIGM-HF trial

AU - Chandra, Alvin

AU - Lewis, Eldrin F.

AU - Claggett, Brian L.

AU - Desai, Akshay S.

AU - Packer, Milton

AU - Zile, Michael R.

AU - Swedberg, Karl

AU - Rouleau, Jean L.

AU - Shi, Victor C.

AU - Lefkowitz, Martin P.

AU - Katova, Tzvetana

AU - McMurray, John J.V.

AU - Solomon, Scott D.

PY - 2018/6

Y1 - 2018/6

N2 - IMPORTANCE Health-related quality of life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities. In the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril/valsartan improved overall HRQL compared with enalapril, as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ). OBJECTIVE To examine the effects of sacubitril/valsartan on physical and social activities. DESIGN, SETTING, AND PARTICIPANTS The PARADIGM-HF trialwas a randomized, double-blind, active treatment-controlled clinical trial performed from December 8, 2009, to March 31, 2014, in 8399 patients with New York Heart Association class II to IV disease and a left ventricular ejection fraction of 40% or less at 1043 centers in 38 countries. Data analysis was performed from August 1, 2017, to December 25, 2017. INTERVENTIONS Sacubitril/valsartan, 200mg twice daily, or enalapril, 10mg twice daily. MAIN OUTCOMES AND MEASURES Patients completed HRQL assessments using the KCCQ at randomization, 4-month, 8-month, and annual visits. The effect of sacubitril/valsartan on components of the physical and social limitation sections of the KCCQ at 8 months and longitudinally and related biomarkers and clinical outcomes were studied. RESULTS At baseline, 7618 of 8399 patients (90.7%) (mean [SD] age, 64 [11] years; 5987 [78.6%] male and 1631 [21.4%] female) completed the initial KCCQ assessment. Patients reported the greatest limitations at baseline in jogging and sexual relationships. Patients receiving sacubitril/valsartan had significantly better adjusted change scores in most physical and social activities at 8 months and during 36 months compared with those receiving enalapril. The largest improvement over enalapril was in household chores (adjusted change score difference, 2.35; 95%CI, 1.19-3.50; P < .001) and sexual relationships (adjusted change score difference, 2.72; 95%CI, 0.97-4.46; P = .002); both persisted through 36 months (overall change score difference, 1.69 [95%CI, 0.78-2.60], P < .001; and 2.36 [95%CI, 1.01-3.71], P = .001, respectively). CONCLUSIONS AND RELEVANCE In patients with heart failure with reduced ejection fraction, sacubitril/valsartan significantly improved nearly all KCCQ physical and social activities compared with enalapril, with the largest responses in household chores and sexual relationships. In addition to reduced likelihood of cardiovascular death, all-cause mortality, and heart failure hospitalization, sacubitril/valsartan may improve limitations in common activities in these patients.

AB - IMPORTANCE Health-related quality of life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities. In the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril/valsartan improved overall HRQL compared with enalapril, as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ). OBJECTIVE To examine the effects of sacubitril/valsartan on physical and social activities. DESIGN, SETTING, AND PARTICIPANTS The PARADIGM-HF trialwas a randomized, double-blind, active treatment-controlled clinical trial performed from December 8, 2009, to March 31, 2014, in 8399 patients with New York Heart Association class II to IV disease and a left ventricular ejection fraction of 40% or less at 1043 centers in 38 countries. Data analysis was performed from August 1, 2017, to December 25, 2017. INTERVENTIONS Sacubitril/valsartan, 200mg twice daily, or enalapril, 10mg twice daily. MAIN OUTCOMES AND MEASURES Patients completed HRQL assessments using the KCCQ at randomization, 4-month, 8-month, and annual visits. The effect of sacubitril/valsartan on components of the physical and social limitation sections of the KCCQ at 8 months and longitudinally and related biomarkers and clinical outcomes were studied. RESULTS At baseline, 7618 of 8399 patients (90.7%) (mean [SD] age, 64 [11] years; 5987 [78.6%] male and 1631 [21.4%] female) completed the initial KCCQ assessment. Patients reported the greatest limitations at baseline in jogging and sexual relationships. Patients receiving sacubitril/valsartan had significantly better adjusted change scores in most physical and social activities at 8 months and during 36 months compared with those receiving enalapril. The largest improvement over enalapril was in household chores (adjusted change score difference, 2.35; 95%CI, 1.19-3.50; P < .001) and sexual relationships (adjusted change score difference, 2.72; 95%CI, 0.97-4.46; P = .002); both persisted through 36 months (overall change score difference, 1.69 [95%CI, 0.78-2.60], P < .001; and 2.36 [95%CI, 1.01-3.71], P = .001, respectively). CONCLUSIONS AND RELEVANCE In patients with heart failure with reduced ejection fraction, sacubitril/valsartan significantly improved nearly all KCCQ physical and social activities compared with enalapril, with the largest responses in household chores and sexual relationships. In addition to reduced likelihood of cardiovascular death, all-cause mortality, and heart failure hospitalization, sacubitril/valsartan may improve limitations in common activities in these patients.

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