Effects of Sacubitril-Valsartan, versus Valsartan, in Women Compared to Men with Heart Failure and Preserved Ejection Fraction: Insights from PARAGON-HF

McMurray, J. J.V. et al. (2020) Effects of Sacubitril-Valsartan, versus Valsartan, in Women Compared to Men with Heart Failure and Preserved Ejection Fraction: Insights from PARAGON-HF. Circulation, 141(5), pp. 338-351. (doi: 10.1161/CIRCULATIONAHA.119.044491) (PMID:31736337)

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Abstract

Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction (HFpEF), the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women, compared with men. In a pre-specified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial which compared sacubitril-valsartan and valsartan in patients with HFpEF. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older, had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI 0.59-0.90) in women and 1.03 (0.84-1.25) in men; P interaction=0.017. The benefit from sacubitril-valsartan was due to reduction in heart failure hospitalization. The improvement in NYHA class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in KCCQ-CSS was less in women than in men. The difference in adverse events, between sacubitril-valsartan and valsartan, was similar in women and men. As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. While the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding. URL: https://clinicaltrials.gov Unique Identifier: NCT01920711.

Item Type:Articles
Additional Information:JJVM is supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217) and AMJ is supported by a British Heart Foundation Clinical Research Training Fellowship (FS/18/14/33330).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jackson, Dr Alice and Jhund, Dr Pardeep and McMurray, Professor John
Authors: McMurray, J. J.V., Jackson, A. M., Lam, C. S.P., Redfield, M. M., Anand, I. S., Ge, J., Lefkowitz, M. P., Maggioni, A. P., Martinez, F., Packer, M., Pfeffer, M. A., Pieske, B., Rizkala, A. R., Sabarwal, S. V., Shah, A. M., Shah, S. J., Shi, V. C., van Veldhuisen, D. J., Zannad, F., Zile, M. R., Cikes, M., Goncalvesova, E., Katova, T., Kosztin, A., Lelonek, M., Sweitzer, N. K., Vardeny, O., Claggett, B., Jhund, P. S., and Solomon, S. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Circulation
Publisher:American Heart Association
ISSN:0009-7322
ISSN (Online):1524-4539
Published Online:17 November 2019
Copyright Holders:Copyright © 2019 American Heart Association, Inc.
First Published:First published in Circulation 141(5):338–351
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science
301144The epidemiology of peripartum cardiomyopathy in a Western European country: An analysis of the Scottish population 1990-2016Pardeep JhundBritish Heart Foundation (BHF)FS/18/14/33330Institute of Cardiovascular & Medical Sciences