Sacubitril/Valsartan Outperforms ACEs/ARBs for HFrEF

Nicholas Tan, MD, MS

New data suggest sacubitril/valsartan (Entresto) could reduce the risk of death and hospitalization compared to use of ACE/ARBs in patients with heart failure with reduced ejection fraction (HFrEF).

Results of the study indicate sacubitril/valsartan was associated with lower risks of death and hospitalization when compared to ACE/ARBs in a cohort of patients with HFrEF in a clinical setting.

Using the OptumLabs Data Warehouse, investigators from the Mayo Clinic of Rochester conducted a retrospective review claims data of patients aged 18 years and older from July 2015 through February 2018. For inclusion in the study, patients were required to have 180 or more days of continuous enrollment with prescription overage before index medication fill date to ensure adequate capture of baseline characteristics.

For the purpose of the investigators’ analysis, the index date of sacubitril/valsartan was a patient's first prescription of sacubitril/valsartan, and the index date of the ACE/ARBs cohort was the first fill of an ACE/ARBs prescription after 180 days of enrollment. Patients in the sacubitril/valsartan group could have ACE/ARB prescription before the index date.

Patients were followed until end of treatment, which investigators defined as discontinuation of index medication, end of enrollment in health plan, death, or end of the study period. The investigators’ primary outcome of interest was a composite of all-cause mortality or all-cause hospitalization. The secondary outcomes of the study included all-cause mortality, all-cause hospitalization, and heart failure hospitalization.

Using propensity scores to match patients on 29 clinical variables, a total of 7893 matched pairs, with a median follow-up of 6.34 months, were included in the analysis. Investigators pointed out one-third of patients were women, 20% were black, and mean medical possession ratio was high for both medication groups.

The primary outcome occurred in 1764 (22.3%) patients treated with sacubitril/valsartan and 2110 (26.1%) patients taking ACE/ARBs. Based on the results, investigators ululated sacubitril/valsartan wax associated with a lower risk of all-cause mortality or all-cause hospitalization during follow-up (HR: 0.86; 95% CI, 0.81 to 0.91; P <.001).

Additionally, sacubitril/valsartan was associated with lower risk of both parts of the primary endpoint but not for heart failure hospitalization (HR: 1.07, 95% CI, 0.96 to 1.19; P = .26). Investigators noted a lower risk of the primary outcome in the sacubitril/valsartan group in white patients (HR: 0.83, 95% CI, 0.76 to 0.90) but not among black patients (HR: 1.00, 95% CI, 0.88 - 1.15; P = .032).

Based on the results of their analyses, investigators suggest sacubitril/valsartan was associated with lowered risk of death and hospitalization compared with ACE/ARBs. However, they pointed out their findings regarding the efficacy of sacubitril/valsartan and ACE/ARBs in black versus white patients need further evaluation.

This study, titled “Comparative Effectiveness of Sacubitril-Valsartan Versus ACE/ARB Therapy in Heart Failure With Reduced Ejection Fraction,” was published online in JACC: Heart Failure.