Sacubitril/Valsartan Adherence and Postdischarge Outcomes Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction

JACC Heart Fail. 2021 Dec;9(12):876-886. doi: 10.1016/j.jchf.2021.06.018. Epub 2021 Sep 8.


Objectives: The authors sought to investigate associations between sacubitril/valsartan adherence and clinical outcomes after hospitalization for heart failure with reduced ejection fraction (HFrEF).

Background: Sacubitril/valsartan improves outcomes in HFrEF, though the extent to which medication adherence is associated with outcomes in routine care is less well characterized.

Methods: The authors analyzed patients aged ≥65 years hospitalized for HFrEF within the Get With the Guidelines-Heart Failure registry linked with Medicare claims between October 2015 and September 2018 who were discharged with sacubitril/valsartan. Sacubitril/valsartan adherence was assessed using medication fills to calculate proportion of days covered (PDC) through 90 days postdischarge. Associations between postdischarge adherence (PDC < or ≥80%) and risk of readmission and death within 1 year were examined by comparing cumulative incidences and adjusted event rates.

Results: Among 897 patients prescribed sacubitril/valsartan at discharge, 295 (32.9%) had PDC ≥80% and 602 (67.1%) had PDC <80%. Baseline characteristics were balanced between groups. Compared with patients with PDC <80%, patients with PDC ≥80% had a significantly lower adjusted hazard of all-cause rehospitalization (HR: 0.66 [95% CI: 0.48-0.89]) and death (HR: 0.42 [95% CI: 0.22-0.79]) at 90 days and at 1 year (HR: 0.69 [95% CI: 0.56-0.86] and HR: 0.53 [95% CI: 0.38-0.74], respectively). For every 5 percentage point increase in PDC, patients experienced a significant reduction in rehospitalization (HR: 0.98 [95% CI: 0.97-0.99]) and death (HR: 0.96 [95% CI: 0.94-0.97]) at 1 year.

Conclusions: In patients hospitalized for HFrEF and discharged on sacubitril/valsartan, high adherence to sacubitril/valsartan within 90 days after discharge was associated with substantially lower rates of readmission and death. Additional efforts to improve adherence with sacubitril/valsartan and other guideline-directed medical therapies in HFrEF are warranted.

Keywords: ARNI; HFrEF; adherence; sacubitril/valsartan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aftercare
  • Aged
  • Aminobutyrates / therapeutic use
  • Angiotensin Receptor Antagonists / therapeutic use
  • Biphenyl Compounds
  • Drug Combinations
  • Heart Failure* / chemically induced
  • Heart Failure* / drug therapy
  • Hospitalization
  • Humans
  • Medicare
  • Patient Discharge
  • Stroke Volume
  • Tetrazoles / therapeutic use
  • United States / epidemiology
  • Valsartan / therapeutic use


  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Drug Combinations
  • Tetrazoles
  • sacubitril
  • Valsartan