Sex Influence on the Efficacy and Safety of Sacubitril/Valsartan

Abstract

Background: Women are underrepresented in sacubitril/valsartan (SV) clinical trials. The aim of this study was to assess sex-specific differences in efficacy, tolerability, and safety of SV in real-world heart failure with reduced ejection fraction (HFrEF) patients. Methods: A prospective registry in 10 centers including all patients who started SV during the last 6 months was analyzed in this study. Results: A total of 427 patients were included, 126 (29.5%) were women. There were no substantial differences in HFrEF treatment before SV initiation, although fewer women than men carried an implantable cardioverter defibrillator (57 [45.2%] vs. 173 [58.1%], p = 0.02). SV starting dose was 24/26 mg b.i.d. in 206 patients (48.2%), 49/51 mg b.i.d. in 184 (43.1%), and 97/103 mg b.i.d. in 34 (8.2%), without relevant differences associated to sex. There were no losses during a mean follow-up of 7.0 ± 0.1 months. The proportion of patients who discontinued the drug (16 [12.7%] women vs. 33 [11.0%] men, p = 0.66) or presented SV-related adverse effects (31 [24.6%] women vs. 79 [26.5%] men, p = 0.72) was also similar in both sexes. However, female sex was an independent predictor of functional class improvement in the multivariate analysis (odds ratio 2.33, 95% confidence interval: 1.24–4.38, p = 0.04). Conclusions: SV in women with HFrEF has a similar tolerability as in men. Females seem to have a more frequent functional class improvement than males.

Effects of Sacubitril/Valsartan on the Right Ventricular Arterial Coupling in Patients with Heart Failure with Reduced Ejection Fraction

“…These findings are in agreement with those of previous studies, which showed that sacubitril/valsartan therapy resulted in an equal inverse remodelling of the LV in women, diabetic individuals, and ischemic heart disease patients [ 37 , 38 , 39 ].…”

Sacubitril/valsartan in real‐life European patients with heart failure and reduced ejection fraction: a systematic review and meta‐analysis

“…All cause-mortality was reported in five studies covering 684 subjects, with the incidence rate being 8 (95% CI 4-12)/100 person-year. 11,18,19,26,27 The hospitalization rate, as inferred by three studies with 390 patients in total, was 24 (95% CI 5-42)/100 person-year. 11,17,18 While there was no relationship between age or sex and all-cause mortality, male sex was negatively associated with hospitalization (weighted linear regression, β = À2.44, 95% CI À4.04 to À0.84; P = 0.03).…”

Real-World Safety of Sacubitril/Valsartan in Women and Men With Heart Failure and Reduced Ejection Fraction: A Meta-analysis

“…Therefore, we could not adjust for patient-level characteristics. Fourth, all of our studies were completed in countries with predominant White populations (9,(13)(14)(15)(16). Consequently, our findings could not be extrapolated to other races.…”