Sacubitril/valsartan and frailty in patients with heart failure and preserved ejection fraction

Butt, J. H. et al. (2022) Sacubitril/valsartan and frailty in patients with heart failure and preserved ejection fraction. Journal of the American College of Cardiology, 80(12), pp. 1130-1143. (doi: 10.1016/j.jacc.2022.06.037) (PMID:36050227)

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Abstract

Background: Frailty is an increasingly common problem, and frail patients are less likely to receive new pharmacologic therapies because the risk–benefit profile is perceived to be less favorable than in nonfrail patients. Objectives: This study investigated the efficacy of sacubitril/valsartan according to frailty status in 4,796 patients with heart failure with preserved ejection fraction randomized in the PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial. Methods: Frailty was measured by using the Rockwood cumulative deficit approach. The primary endpoint was total heart failure hospitalizations or cardiovascular death. Results: A frailty index (FI) was calculable in 4,795 patients. In total, 45.2% had class 1 frailty (FI ≤0.210, not frail), 43.5% had class 2 frailty (FI 0.211-0.310, more frail), and 11.4% had class 3 frailty (FI ≥0.311, most frail). There was a graded relationship between FI class and the primary endpoint, with a significantly higher risk associated with greater frailty (class 1: reference; class 2 rate ratio: 2.19 [95% CI: 1.85-2.60]; class 3 rate ratio: 3.29 [95% CI: 2.65-4.09]). The effect of sacubitril/valsartan vs valsartan on the primary endpoint from lowest to highest FI class (as a rate ratio) was: 0.98 [95% CI: 0.76-1.27], 0.92 [95% CI: 0.76-1.12], and 0.69 [95% CI: 0.51-0.95]), respectively (Pinteraction = 0.23). When FI was examined as a continuous variable, the interaction with treatment was significant for the primary outcome (Pinteraction = 0.002) and total heart failure hospitalizations (Pinteraction < 0.001), with those most frail deriving greater benefit. Conclusions: Frailty was common in heart failure with preserved ejection fraction and associated with worse outcomes. Compared with valsartan, sacubitril/valsartan seemed to show a greater reduction in the primary endpoint with increasing frailty, although this was not significant when FI was examined as a categorical variable. (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Butt, Mr Jawad and Jhund, Professor Pardeep and Dewan, Dr Pooja and McMurray, Professor John
Authors: Butt, J. H., Dewan, P., Jhund, P. S., Anand, I. S., Atar, D., Ge, J., Desai, A. S., Echeverria, L. E., Køber, L., Lam, C. S.P., Maggioni, A. P., Martinez, F., Packer, M., Rouleau, J. L., Sim, D., Van Veldhuisen, D. J., Vrtovec, B., Zannad, F., Zile, M. R., Gong, J., Lefkowitz, M. P., Rizkala, A. R., Solomon, S. D., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Journal of the American College of Cardiology
Publisher:Elsevier
ISSN:0735-1097
ISSN (Online):1558-3597
Published Online:29 August 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Journal of the American College of Cardiology 80(12): 1130-1143
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science