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Original Investigation
June 2018

Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial

Author Affiliations
  • 1Brigham and Women’s Hospital, Boston, Massachusetts
  • 2Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas
  • 3Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston
  • 4Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
  • 5National Heart and Lung Institute, Imperial College, London, England
  • 6Institut Cardiologie de Montreal, Université de Montreal, Montreal, Quebec, Canada
  • 7Novartis, East Hanover, New Jersey
  • 8National Hospital of Cardiology, Sofia, Bulgaria
  • 9British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland
JAMA Cardiol. 2018;3(6):498-505. doi:10.1001/jamacardio.2018.0398
Key Points

Question  Compared with enalapril, does sacubitril/valsartan improve specific physical or social activities in patients with heart failure and reduced ejection fraction?

Findings  In this post hoc secondary analysis of 8399 patients from the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, limitations in physical and social activities were significantly improved in almost all domains in patients randomized to receive sacubitril/valsartan, compared with enalapril. The largest improvement was seen in limitations of sexual activity.

Meaning  In addition to improving morbidity and mortality, sacubitril/valsartan may significantly improve limitations in physical and social activities that are common in patients with heart failure, including sexual activities.

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 trial was 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, 200 mg twice daily, or enalapril, 10 mg 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.

Trial Registration  clinicaltrials.gov Identifier: NCT01035255

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