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Sacubitril/Valsartan Adherence Drop Linked to Lower Household Income


Entresto (sacubitril/valsartan) is approved for use in adult and pediatric heart failure, and previous research shows it to be cost-effective in the long term.

Two forms of adherence to Entresto (sacubitril/valsartan), claim and medication, were hindered by lower overall household income, report the authors of a new study published in Circulation: Cardiovascular Quality and Outcomes. Previous research shows the combination medication is effective at reducing heart failure (HF)–related hospitalization, improving cardiac function, and decreasing mortality, they emphasized.

The angiotensin receptor neprilysin inhibitor is approved to treat HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fractions (HFrEF) in adult patients, as well as symptomatic disease with systemic left ventricular systolic dysfunction in pediatric patients 1 year and older. For this study, the investigators focused on HFrEF; the HFpEF indication had not yet been approved.

Patients included in the final analysis (N = 135,282) had a claim for a sacubitril/valsartan prescription in the 6 months after their HFrEF diagnosis and 6 or more months of continuous Optum enrollment in 2016 to 2020, and the investigators defined their adherence as 80% or more of days covered and evaluated this among 10,836 patients with a claim in the year of after their second HFrEF diagnosis. Their data were provided by the Optum de-identified Clinformatics Data Mart—covering patients with commercial or Medicare health coverage—and covariates investigated for their influence on outcomes were age, sex, race, ethnicity, educational attainment, US region, number of prescribed medications, and Elixhauser Comorbidity Index.

“Outcomes in HFrEF are influenced by access and adherence to guideline-directed medical therapy,” the authors wrote. “We hypothesized that lower annual household income is associated with decreased odds of having a claim for and adhering to sacubitril/valsartan.”

Results show 4.7% of the patient cohort had a sacubitril/valsartan script within 6 months of their HFrEF diagnosis. Patient ages ranged from 74.2 to 75.7 years. Household incomes were categorized into 6 levels: less than $40,000; $40,000 to $49,999; $50,000 to $59,999; $60,000 to $74,999; $75,000 to $99,999; and $100,000 or higher. Patients of a White ethnicity accounted for most participants in each of these ranges, from 63.3% of those with a household income below $40,000 to 82.1% of those with an income exceeding $100,000. Those who were an Asian ethnicity represented the fewest patients in each income bracket, from 1.5% to 3.7%, respectively.

Although total cardiology visits were equivalent overall and across all income levels, at 2, patients in the highest income bracket has the fewest median (IQR) days between their first and second HF diagnoses, at 21 (9-76). The overall median was 23 (9-80) days.

Medicare Part D enrollment was highest (92.2%) among those with an annual household income below $40,000 and lowest (76.7%) for those at $100,000 or more. Medicaid-Medicare dual enrollment was also highest among those in the lowest income bracket (15.7%) and lowest in the highest income bracket (2.3%).

An overall 30% reduced chance of filing a sacubitril/valsartan claim (odds ratio [OR], 0.70; 95% CI, 0.65-0.75) was seen for those in the lowest income category, and a similar result was seen after adjusting for clinical and socioeconomic factors (OR, 0.83; 95% CI, 0.76-0.90). Lower odds of claim presentation were also linked with older age and female sex and higher odds if patients were of Black or Hispanic ethnicity.

Close to three-quarters (73.7%) of the patients were adherent, with woman 11% more likely than men to meet the PDC threshold set by the investigators. Lower odds of being adherent were seen among Black patients, (OR, 0.64; 95% CI, 0.57-0.72), Hispanic patients (OR, 0.62; 95% CI, 0.55-0.71), and the lowest vs the highest income bracket (OR, 0.70; 95% CI, 0.59-0.83).

Overall, the authors found lower odds of a patient filing a sacubitril/valsartan claim if they were in the lowest income bracket, both before and after multivariate adjustment; these odds increased, however, with the higher brackets. There is still a gap in care despite increases in both prescriptions for and adherence to sacubitril/valsartan, the authors noted.

“Patients who are prescribed guideline-directed medical therapy have better HF outcomes, irrespective of income or drug cost,” they wrote. “Yet, clinical inertia may prevent clinicians from changing or optimizing medications.”

They added that with long-term adherence being difficult to maintain among most patients, multifaceted strategies are needed to better results, including incorporating community health workers and utilizing fixed-dose combination regimens.

“Future analyses will be helpful to determine other social factors [beyond household income] associated with a delay in sacubitril/valsartan initiation and mediators of long-term adherence,” the authors concluded.


Johnson AE, Swabe GM, Addison D, et al. Relation of household income to access and adherence to combination sacubitril/valsartan in heart failure: a retrospective analysis of commercially insured patients. Circ Cardiovasc Qual Outcomes. 2022;15(7):e009179. doi:10.1161/CIRCOUTCOMES.122.009179

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