Clinical Outcomes Associated With In-Hospital Versus Delayed Outpatient Initiation of Sacubitril/Valsartan in Patients With Heart Failure With Reduced Ejection Fraction

Background: Heart failure with reduced ejection fraction (HFrEF) remains associated with high rates of hospitalization and early readmission, with approximately 20-25% of patients readmitted within 30 days. Sacubitril/valsartan is a key component of guideline-directed medical therapy, but the optimal timing of initiation during hospitalization versus after discharge remains uncertain. Objective: This study aimed to evaluate whether initiation of sacubitril/valsartan during hospitalization is associated with improved short-term outcomes compared with delayed outpatient initiation. Methods: This retrospective cohort study used the MIMIC-IV database. Adult patients hospitalized with HFrEF who received sacubitril/valsartan were included. Patients were classified into in-hospital initiation and delayed outpatient initiation groups based on medication timing. The primary outcome was 30-day hospital readmission, and the secondary outcome was in-hospital mortality. Multivariable logistic regression was used to assess associations after adjustment for age, sex, race, and the Charlson Comorbidity Index. Results: A total of 4,156 hospitalizations were included. There was no significant association between timing of sacubitril/valsartan initiation and 30-day readmission (aOR=0.91; 95% CI: 0.50-1.67; p=0.764). Higher comorbidity burden was associated with increased readmission risk (aOR=1.04; 95% CI: 1.00-1.07; p=0.035). No significant difference in in-hospital mortality was observed between groups. Conclusion: Timing of sacubitril/valsartan initiation was not associated with short-term outcomes. Comprehensive management strategies beyond the timing of therapy may be important for improving outcomes in this population.