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.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.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.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.https://www.clinicaltrials.gov. Unique identifier: NCT01920711.
