Improvements in Quality of Life

ENTRESTO is indicated in adult patients for the treatment of symptomatic chronic heart failure with reduced ejection fraction.⁹

* As measured by an analysis model that incorporated age and treatment effect. This analysis model was included in a secondary analysis of PARADIGM-HF that examined the effect of ENTRESTO on components of the physical and social limitation section of the KCCQ at 8 months, and longitudinally over 36 months. Patients in the ENTRESTO group had significantly better adjusted change scores in 7 out of 10 physical and social activities vs the enalapril group. The largest improvements over enalapril were in household chores (adjusted change score difference, 2.35 [95% CI, 1.19⁠–⁠3.50], P<0.001) and sexual relationships (adjusted change score difference, 2.72 [95% CI: 0.97–4.46], P=0.002); both persisted through 36 months (overall change score difference, 1.69 [95% CI: 0.78–2.60], P<0.001; and 2.36 [95% CI: 1.01–3.71], P=0.001, respectively).¹ PARADIGM-HF was a multinational, randomised, double-blind trial comparing ENTRESTO to enalapril in 8,442 symptomatic (NYHA Class II-IV) HFrEF patients (LVEF ≤40%, amended later to ≤35%). For the primary endpoint, composite of CV death or first HF hospitalisation, ENTRESTO was superior to enalapril (P<0.0001). The median follow-up duration was 27 months.¹⁰
† Post hoc analysis of PARADIGM-HF that examined the changes in KCCQ scores at randomisation, Month 4, Month 8, Month 12, and annually thereafter through final visit. 91% of patients enrolled in PARADIGM-HF (n=7,623/8,399) completed the KCCQ at randomisation, with complete data at 8 months for 6,881 patients (90% of baseline). At Month 8, the ENTRESTO group noted improvements in both KCCQ clinical summary score (+0.64 vs -0.29; P=0.008) and KCCQ overall summary score (+1.13 vs -0.14; P<0.001) in comparison to the enalapril group, as well as a significantly smaller proportion of patients with deterioration (≤5 points decrease) of both KCCQ scores (27% vs 31%; P=0.01). Adjusted change scores demonstrated consistent improvements in ENTRESTO vs enalapril through 36 months. Patients who died or did not complete the 8-month KCCQ score were excluded from the principal analysis.²
‡ KCCQ is a self-administered, health-related, QoL measure for HF patients that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and QoL on a scale of 0–100, with higher scores indicating fewer symptoms and physical limitations associated with HF. 7,618 of 8,399 patients from the PARADIGM-HF trial completed the initial KCCQ assessment.²
§ LSM estimation (SE) ENTRESTO vs enalapril: 0.80 (20) vs -0.39 (-0.20). LSM estimates (SE) difference: 1.19 (0.28), P<0.001.²

ACEi, angiotensin-converting enzyme inhibitor; CI, confidence interval; CV, cardiovascular; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HRQoL, health-related quality of life; KCCQ, Kansas City Cardiomyopathy Questionnaire; LSM, least squares mean; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; QoL, quality of life; SE, standard error.

References:

1. Chandra A, et al. JAMA Cardiol 2018;3(6):498–505.
2. Lewis EF, et al. Circ Heart Fail 2017;10(8):e003430.
3. Heo S, et al. Heart Lung 2009;38(2):100–108.
4. Claggett B, et al. N Engl J Med 2015;373(23):2289–2290.
5. Heidenreichet J al. JACC  2022;79(17):e263-e421
6. ENTRESTO Summary of Product Characteristics. Accessed December 2021 at www.medicines.ie
7. McDonagh T, et al. Eur Heart J 2021;42(36):3599-3726.
8. McMurray JJ, et al. N Engl J Med 2014;371:993–1004.