Effects of Sacubitril-Valsartan Versus Valsartan in Women Compared With Men With Heart Failure and Preserved Ejection Fraction Insights From PARAGON-HF

John J.V. McMurray*, Alice M. Jackson, Carolyn S.P. Lam, Margaret M. Redfield, Inder S. Anand, Junbo Ge, Marty P. Lefkowitz, Aldo P. Maggioni, Felipe Martinez, Milton Packer, Marc A. Pfeffer, Burkert Pieske, Adel R. Rizkala, Shalini V. Sabarwal, Amil M. Shah, Sanjiv J. Shah, Victor C. Shi, Dirk J. van Veldhuisen, Faiez Zannad, Michael R. ZileMaja Cikes, Eva Goncalvesova, Tzvetana Katova, Anamaria Kosztin, Malgorzata Lelonek, Nancy Sweitzer, Orly Vardeny, Brian Claggett, Pardeep S. Jhund, Scott D. Solomon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

257 Scopus citations


BACKGROUND: Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction, the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women compared with men. METHODS: In a prespecified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), which compared sacubitril-valsartan and valsartan in patients with heart failure with preserved ejection fraction. 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. RESULTS: Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older and had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP (N-terminal pro–B-type natriuretic peptide) 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 (95% CI, 0.84–1.25) in men (P interaction = 0.017). The benefit from sacubitril-valsartan was attributable to reduction in heart failure hospitalization. The improvement in New York Heart Association class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in Kansas City Cardiomyopathy Questionnaire clinical summary score was less in women than in men. The difference in adverse events between sacubitril-valsartan and valsartan was similar in women and men. CONCLUSIONS: As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. Whereas 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.

Original languageEnglish (US)
Pages (from-to)338-351
Number of pages14
Issue number5
StatePublished - Feb 4 2020


  • heart failure
  • hospitalization
  • neprilysin
  • women

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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