(P-138) Effectiveness of Sacubitril/valsartan versus Aldosterone Antagonists for Prevention of Heart Failure-related and All-cause Hospitalization in Heart Failure with Reduced Ejection Fraction

Background: Heart Failure (HF) is a leading cause of hospitalization in the U.S. Effectiveness of sacubitril/valsartan (SAC/VAL) compared to enalapril in reducing risk of HF hospitalization and death was demonstrated in PARADIGM-HF trial. The 2017 American Heart Association HF guidelines recommended SAC/VAL or aldosterone receptor antagonists (ARA) as step 2 therapy for stage C HF with reduced ejection fraction (HFrEF).

Objectives: This study aimed to compare effectiveness of SAC/VAL versus an ARA for preventing HF-related and all-cause hospitalization in patients with HFrEF undergoing regimen titrations.

Methods: We conducted a retrospective cohort study of patients with HFrEF using the IBM® MarketScan® claims databases from 1st January 2014 to 31st December 2018. Patients were included if they were aged ≥18 years, had first HFrEF (identified via ICD-9/ICD-10 codes) hospital admission on or after 1st January 2015, and initiated SAC/VAL or an ARA after HF discharge. Patients also had ≥1-year continuous eligibility prior to the HFrEF admission (baseline period). Patients were excluded if they initiated SAC/VAL or ARA therapy during the baseline period. Initiation date of SAC/VAL or ARA was the index date. Follow-up continued until first hospitalization, switch to comparator, or end of enrollment. After 1:3 (SAC/VAL:ARA) propensity score (PS) matching, we employed Cox proportional hazards regression with robust variance estimator to compare HF-related and all-cause hospitalization between groups. Subgroup and sensitivity analyses assessed robustness of the main analysis.

Results: After PS matching, 1,088 SAC/VAL and 2,839 ARA new users were included. The crude incidence of HF-related hospitalization was 13 per 100 person-years for SAC/VAL users and 18 per 100 person-years for ARA users. SAC/VAL users had a 27% lower risk of HF-related hospitalization (adjusted hazard ratio [aHR]: 0.73, 95% confidence interval [CI]: 0.58 - 0.91; p=0.006) and 31% lower risk of all-cause hospitalization (aHR: 0.69, 95% CI: 0.61 - 0.79; p<0.001) compared to ARA users. Subgroup analyses found no significant heterogeneity, including among those with or without chronic kidney disease or coronary artery disease.

Conclusions: SAC/VAL was associated with lower risk of HF-related and all-cause hospitalizations compared to ARA. Our findings suggest that SAC/VAL may provide additional risk reduction compared with ARAs, for patients with HFrEF who initiate either SAC/VAL or ARA. Future research is needed to assess the benefits and risks of combined initiation of these drugs.