Clinical Impact of the Early Use of Sacubitril/Valsartan in Newly Diagnosed Heart Failure and Reduced Ejection Fraction

Background: To investigate the clinical impact of early sacubitril/valsartan initiation on clinical outcomes and left ventricular reverse remodeling in patients with newly diagnosed heart failure with reduced ejection fraction (HFrEF). Methods: Patients with newly diagnosed HFrEF and prescriptions for sacubitril/valsartan were identified from a multi-institutional database in Taiwan from 2016 to 2020. The patients were categorized as early users if they initiated sacubitril/valsartan within 6 months of the initial diagnosis, and late users if they initiated sacubitril/ valsartan 6 months or more after the diagnosis. Clinical outcomes and changes in left ventricular ejection fraction (LVEF) assessed by echocardiography were compared between the early and late users after inverse probability of treatment weighting (IPTW) adjustment. Results: Among the 410 enrolled patients, 188 were early users and 222 were late users. The early users were younger and had a lower LVEF, while the late users had higher rates of hypertension, diabetes, dyslipidemia, and chronic kidney disease. After IPTW, the two groups had similar baseline characteristics. There were no significant differences in the incidence rates of all-cause death, cardiovascular death, and heart failure hospitalization before and after IPTW. However, post-IPTW, the early user group had a lower risk of cumulative emergency department visits (hazard ratio: 0.84, 95% confidence interval: 0.7 1-0.99; p = 0.0353). Both groups demonstrated reverse remodeling, with an increase in LVEF from 28.7% to 45.3% in the early users, and from 28.9% to 40.1% in the late users, which was significantly more prominent in the early users (p < 0.0001). Conclusions: In patients with newly-diagnosed HFrEF, the early initiation of sacubitril/valsartan was associated with a lower risk of the cumulative number of emergency visits and a greater improvement in LVEF.