Effectiveness of sacubitril/valsartan versus aldosterone antagonists in heart failure with reduced ejection fraction: A retrospective cohort study

Abstract

Study objective: To assess the effectiveness of sacubitril/valsartan versus angiotensin receptor antagonist therapy for prevention of heart failure (HF)-related hospitalization and all-cause hospitalization in a large cohort of patients with heart failure with reduced ejection fraction (HFrEF).

Design: Retrospective cohort study.

Data source: IBM^® MarketScan^® research databases (2014-2018).

Patients: Patients aged 18 years or older with their first HFrEF hospitalization on or after January 1, 2015, who initiated sacubitril/valsartan or angiotensin receptor antagonist after hospital discharge.

Intervention: Sacubitril/Valsartan versus Angiotensin receptor antagonist.

Measurements and main results: The index date was the first sacubitril/valsartan or angiotensin receptor antagonist fill date. After 1 up to 3 propensity score matching, Cox proportional hazards regression was used with robust variance estimators to compare HF-related and all-cause hospitalizations between treatments. Subgroup and sensitivity analyses were conducted to assess the robustness of the main analysis. After propensity score matching, 1,088 sacubitril/valsartan and 2,839 angiotensin receptor antagonist new users were included. The crude incidence of HF-related hospitalization was 13 per 100 person-years for sacubitril/valsartan users and 18 per 100 person-years for angiotensin receptor antagonist users. Compared with angiotensin receptor antagonist use, sacubitril/valsartan use was associated with 27% lower risk of HF-related hospitalization (adjusted hazard ratio, 0.73; 95% confidence interval, 0.58-0.91; p = 0.006) and 31% lower risk of all-cause hospitalization (adjusted hazard ratio, 0.69; 95% confidence interval, 0.61-0.79; p < 0.001). Subgroup analyses revealed no significant heterogeneity, including subpopulations with chronic kidney disease or coronary artery disease.

Conclusions: Compared with angiotensin receptor antagonists, sacubitril/valsartan was associated with lower risk of HF-related and all-cause hospitalizations. Our data suggest that, when added sequentially, sacubitril/valsartan should be the preferred initial agent over angiotensin receptor antagonists.

Keywords: HF-related hospitalization; all-cause hospitalization; angiotensin receptor-neprilysin inhibitor; real-world evidence; sacubitril/valsartan.