Treatment with sacubitril-valsartan was found to be associated with lower risks for death and hospitalization compared with treatment with angiotensin-converting enzyme inhibitor (ACE)/angiotensin receptor blocker (ARB) in patients with systolic heart failure (HF) with reduced ejection fraction (HFrEF), according to a study published in JACC Heart Failure.

Sacubitril is a neprilysin inhibitor and valsartan is an angiotensin II receptor blocker. This drug combination was found to reduce all-cause mortality and hospitalization for HF by 16% and 21%, respectively in patients with HFrEF, in the PARADIGM-HF trial ( identifier: NCT01035255).

In this retrospective study, investigators analyzed deidentified claims data of patients with systolic HFrEF enrolled in private insurance or Medicare Advantage. A 1:1 propensity score match was applied to balance patients who filled a prescription for sacubitril-valsartan (n = 7893) or ACE/ARB (n = 7893). The primary outcome was a composite of all-cause mortality and hospitalization. Secondary outcomes were all-cause mortality, all-cause hospitalization, and HF hospitalization.

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Patients treated with sacubitril-valsartan vs ACE/ARB had reduced mortality (2.2% vs 2.9%, respectively; hazard ratio [HR], 0.80; 95% CI, 0.66-0.97; P =.027; mean follow-up, 6.3 months) and all-cause hospitalization (21.8% vs 26.1%, respectively; HR, 0.86; 95% CI, 0.80-0.91; P <.001). The risk for HF hospitalization was comparable in the 2 groups (HR, 1.07; 95% CI, 0.96-1.19; P =.26).

White and nonblack patients of other races/ethnicities, but not black, patients treated with sacubitril-valsartan vs ACE/ARB had a lower risk for the primary outcome (whites: HR, 0.83; 95% CI, 0.76-0.90; nonblack: HR, 0.80; 95% CI, 0.69-0.93; blacks: HR, 1.00; 95% CI: 0.88-1.15; interaction P =.032).

Study limitations include its observational nature, the sole inclusion of patients with private and Medicare Advantage plans, and the relatively short follow-up period.

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“More research is needed to determine if there are racial differences in treatment response to sacubitril-valsartan,” concluded the study authors.


Tan NY, Sangaralingham LR, Sangaralingham SJ, Yao X, Shah ND, Dunlay SM. Comparative effectiveness of sacubitril-valsartan versus ACE/ARB therapy in heart failure with reduced ejection fraction. JACC Heart Fail. 2020;8(1):43-54.