Sex differences and clinical outcomes, including ventricular tachyarrhythmias, of patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan

Background: Women with heart failure with reduced ejection fraction (HFrEF) often experience worse clinical outcomes compared to men, including higher rates of mortality, hospitalization, and congestion. However, the effects of sacubitril/valsartan on these outcomes, as well as on ventricular tachyarrhythmias, have not been well studied in women with HFrEF.

Methods: This study included consecutive series of patients treated with sacubitril/valsartan at University Hospital Mannheim from 2016 to 2020. Baseline and follow-up data were compared between women and men. The endpoints included all-cause mortality, ventricular tachyarrhythmias, all-cause hospitalization, and congestion.

Results: A total of 246 patients were analyzed, comprising 50 (20.3%) women and 196 (79.7%) men. The study population consisted of 34.3% ambulatory patients and 65.7% hospitalized patients admitted for acute decompensated or symptomatic HF. The sex distribution was as follows: among women, 48.6% were ambulatory and 51.4% were hospitalized, while among men, 30.6% were ambulatory and 69.4% were hospitalized. Ischemic cardiomyopathy (ICM) was less common as a cause of heart failure (HF) in women than in men (32% vs. 57.7%, p = 0.001). During the 12-month follow-up, left ventricular ejection fraction (LVEF) improved more significantly in women than in men, increasing from 29.0% (10.0-45.0) to 40.0% (15.0-59.0) in women (p = 0.009) compared to an increase from 28.0% (3.0-65.0) to 33.0% (13.0-60.0) in men. There were no significant differences in all-cause mortality at 12-month between women and men (4% vs. 6.7%; p = 0.742). The results indicated no significant differences between the sexes in the incidence of ventricular tachyarrhythmias [ventricular fibrillation [VF] and sustained ventricular tachycardia [VT]] (4.5% vs. 0.6%; p = 0.121) (2.3% vs. 3.9%; p = 1.00), hospitalizations (70.2% vs. 67.8%; p = 0.769), congestion at 12-month follow-up (11.4% vs. 10.1%; p = 0.762). Female sex was not identified as a predictor for the occurrence of ventricular tachyarrhythmias or mortality rate at 12 months [hazard ratio (HR), 0.586; 95%-confidence interval (CI) 0.17-2.016; p = 0.397] (HR, 1.898; 95%-CI 0.381-9.464; p = 0.434).

Conclusion: Women with HFrEF treated with sacubitril/valsartan showed a greater improvement in LVEF compared to men, though clinical outcomes were similar across sexes. Female sex was not a predictor of ventricular tachyarrhythmias or mortality at 12 months.