LAUSR

Background Sacubitril/valsartan has been highly efficacious in randomized clinical trials of patients with HFrEF. However, the effectiveness of sacubitril/valsartan in routine US clinical practice is unclear. Methods This study included patients age ≥65 years who were hospitalized for HFrEF (ejection fraction ≤40%), were eligible for sacubitril/valsartan at discharge, and were enrolled in the Get With The Guidelines-Heart Failure registry linked to Medicare claims between October 2015 and September 2017. Patients prescribed sacubitril/valsartan at discharge were compared with (1) patients not prescribed sacubitril/valsartan, and (2) patients prescribed ACEI/ARB at discharge. Study endpoints were post-discharge mortality and hospitalization outcomes at 12 months. Negative control (falsification) endpoints included hospitalization for urinary tract infection and hospitalization for nutritional disorder. To adjust for selection bias, inverse probability of treatment weighting and adjustment for other HFrEF medications prescribed at discharge were performed. Results Overall, 746 (8.1%) patients were discharged on sacubitril/valsartan and 8,466 (91.9%) were not. Of those not prescribed sacubitril/valsartan, 5,286 (62.4%) were prescribed an ACEI/ARB. As compared with no sacubitril/valsartan, discharge prescription of sacubitril/valsartan was independently associated with lower risk of all-cause mortality, all-cause hospitalization, and the composite of mortality or HF hospitalization at 12-month follow-up (Table). These findings were consistent in comparisons between sacubitril/valsartan and ACEI/ARB. Discharge sacubitril/valsartan prescription was not significantly associated with the negative control endpoints, suggesting the findings were unlikely due to residual confounding. Conclusions In this contemporary real-world population of US patients hospitalized for HFrEF and eligible for sacubitril/valsartan, prescription of sacubitril/valsartan at discharge was independently associated with substantial reductions in post-discharge mortality and hospitalization. These findings suggest that the significant benefits of sacubitril/valsartan observed in clinical trials extend to patients seen in routine US clinical practice.