Frailty and uptake of angiotensin receptor neprilysin inhibitor for heart failure with reduced ejection fraction

Yu Chien Lee, Joshua K. Lin, Darae Ko, Susan Cheng, Elisabetta Patorno, Robert J. Glynn, Theodore Tsacogianis, Dae Hyun Kim*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

3 Scopus citations


Background: Frail older adults may be less likely to receive guideline-directed medical therapy (GDMT)—renin-angiotensin blockers, beta-blockers, and mineralocorticoid receptor antagonists—for heart failure with reduced ejection fraction (HFrEF). We aimed to examine the uptake of angiotensin receptor neprilysin inhibitor (ARNI) and GDMT in frail older adults with HFrEF. Methods: Using 2015–2019 Medicare data, we estimated the proportion of beneficiaries with HFrEF receiving ARNI and GDMT each year by frailty status, defined by a claims-based frailty index. Logistic regression was used to identify clinical characteristics associated with ARNI initiation. Cox proportional hazards regression was used to examine the association of GDMT use in 2015 and death or heart failure hospitalization in 2016–2019. Results: Among 147,506–180,386 beneficiaries with HFrEF (mean age: 77 years; 27% women; 42.6–49.1% frail) in 2015–2019, the proportion of patients receiving ARNI increased in both non-frail (0.4%–16.4%) and frail (0.3%–13.7%) patients (p for yearly-trend-by-frailty = 0.970). Among those not receiving a renin-angiotensin system blocker, patients with age ≥ 85 years (odds ratio [95% CI], 0.89 [0.80–0.99]), dementia (0.88 [0.81–0.96]), and frailty (0.87 [0.81–0.94]) were less likely to initiate ARNI. The proportion of patients receiving all 3 GDMT classes increased in non-frail patients (22.0%–27.0%) but changed minimally in frail patients (19.6%–21.8%). Regardless of frailty status, treatment with at least 1 class of GDMT was associated with lower death or heart failure hospitalization than no GDMT medications (hazard ratio [95% CI], 0.94 [0.91–0.97], 0.92 [0.89–0.94], 0.94 [0.91–0.97] for 1, 2, and 3 classes, respectively). Conclusions: Our results suggest an evidence-practice gap in the use of ARNI and GDMT in Medicare beneficiaries with HFrEF, particularly those with frailty. Efforts to narrow this gap are needed to reduce the burden of HFrEF in older adults.

Original languageEnglish
Pages (from-to)3110-3121
Number of pages12
JournalJournal of the American Geriatrics Society
Issue number10
StatePublished - 10 2023
Externally publishedYes

Bibliographical note

© 2023 The American Geriatrics Society.


  • angiotensin receptor neprilysin inhibitor
  • frailty
  • guideline-directed medical therapy
  • heart failure with reduced ejection fraction
  • Antihypertensive Agents/therapeutic use
  • Ventricular Dysfunction, Left
  • Medicare
  • United States
  • Humans
  • Male
  • Adrenergic beta-Antagonists/therapeutic use
  • Frailty/drug therapy
  • Neprilysin/pharmacology
  • Stroke Volume
  • Heart Failure/drug therapy
  • Receptors, Angiotensin/therapeutic use
  • Aged, 80 and over
  • Female
  • Aged
  • Angiotensin Receptor Antagonists/therapeutic use


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