Pharmacotherapy. 2021 Jun 25. doi: 10.1002/phar.2610. Online ahead of print.
BACKGROUND: Sacubitril/valsartan (SAC/VAL) and aldosterone antagonists (ARAs) are each recommended therapy for heart failure with reduced ejection fraction (HFrEF), but little is known about their comparative effectiveness for preventing HF-related and all-cause hospitalizations in patients previously hospitalized for HFrEF.
METHODS: This retrospective cohort study used MarketScan® research databases (2014-2018) to identify patients aged 18 years or older with their first HFrEF hospitalization on or after January 1, 2015, who initiated SAC/VAL or ARA after hospital discharge. The index date was the first SAC/VAL or ARA 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.
RESULTS: After propensity score 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. Compared with ARA use, SAC/VAL 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.
CONCLUSION: Compared with ARAs, SAC/VAL was associated with lower risk of HF-related and all-cause hospitalizations. Our data suggest that, when added sequentially, SAC/VAL should be the preferred initial agent over ARAs.