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ARNI treatment improves quality of life in HFrEF patients
Literature - Chandra A, Lewis EF, Claggett BL, et al. - JAMA Cardiol. 2018; published online ahead of print

Introduction and methods

PARADIGM-HF (Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) was a randomized, double-blind, active treatment–controlled, clinical trial that enrolled patients ≥18 years with heart failure (HF) and left ventricular ejection fraction (LVEF) ≤40%, NYHA class II-IV, and elevated biomarkers, or a HF-associated hospitalization within 12 months before enrollment [1].

Patients were randomized to enalapril 10mg twice daily, or sacubitril/valsartan 200mg twice daily, in a 1:1 ratio, after a run-in phase to test for intolerance. PARADIGM-HF showed that sacubitril/valsartan, compared with enalapril, significantly reduced CV mortality, HF-associated hospitalization (HFH), and all-cause mortality in patients with HF and reduced LVEF [2]. Health-related quality of life (HRQL) was also assessed, using the Kansas City Cardiomyopathy Questionnaire (KCCQ) [3].

In this secondary analysis of the PARADIGM-HF data, individual physical and social activity items in the KCCQ domains were evaluated, in order to assess the responsiveness of each individual activity to sacubitril/valsartan. The KCCQ is a 23-item, disease-specific questionnaire, which was answered 6 times during the study and was used to assess HRQL at 8 months. Patient’s responses were scaled from 0 to 100, with 0 indicating extremely or severely limited and 100 indicating not at all limited [4].

Main results

  • At randomization, 7618 of 8399 patients (90.7%) completed the initial KCCQ assessment.
  • Sacubitril/valsartan was significantly associated with a 5-point or greater improvement in score in a combined physical and social activity mean score with adjustment for baseline score at 8-month follow-up (OR: 1.12; 95%CI: 1.00-1.24; P = 0.04).

Sacubitril/valsartan was also significantly associated with an improvement of the following activities:

  • walking 100 yd on level ground (OR: 1.13; 95%CI: 1.03-1.24; P = 0.01)
  • gardening (OR: 1.17; 95%CI: 1.07-1.28; P = 0.001)
  • jogging (OR: 1.12; 95%CI: 1.02-1.24; P = 0.02)
  • hobbies (OR: 1.16; 95%CI: 1.05-1.28; P = 0.002)
  • household chores (OR: 1.20; 95%CI: 1.09-1.32; P < 0.001)
  • sexual relationships (OR: 1.18; 95%CI: 1.05-1.33; P = 0.005)

Improvement in combined physical and social activity during 8 months was associated with reduced risk of the primary composite end point of CV death or first HFH (HR: 0.79; 95%CI: 0.70-0.90).


In patients with heart failure and reduced ejection fraction, sacubitril/valsartan significantly improved limitations in physical and social activities compared with enalapril, with the largest response seen in household chores and sexual relationships.


1. McMurray JJ, Packer M, Desai AS, et al; PARADIGM-HF Committees and Investigators. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). Eur J Heart Fail. 2013;15(9):1062-1073.

2. McMurray JJ, Packer M, Desai AS, et al; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004.

3. Lewis EF, Claggett BL, McMurray JJV, et al. Health-related quality of life outcomes in PARADIGM-HF. Circ Heart Fail. 2017;10(8):e003430.

4. Green CP, Porter CB, Bresnahan DR, et al. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure. J AmColl Cardiol.


Find this article online at JAMA Cardiology

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Schedule17 May 2024