Angiotensin receptor‐neprilysin inhibitor adherence and outcomes in heart failure with reduced ejection fraction

Abstract Aims Whether medication adherence to angiotensin receptor‐neprilysin inhibitor (ARNI) in real‐world practice is associated with the reduced risk of all‐cause mortality or hospitalization relative to that with traditional renin–angiotensin system (RAS) blockade remains unclear. This study in...

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Main Authors: Dong‐Hyuk Cho, Jimi Choi, Jong‐Chan Youn, Mi‐Na Kim, Chan Joo Lee, Jung‐Woo Son, Byung‐Su Yoo
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:ESC Heart Failure
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Online Access:https://doi.org/10.1002/ehf2.15117
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author Dong‐Hyuk Cho
Jimi Choi
Jong‐Chan Youn
Mi‐Na Kim
Chan Joo Lee
Jung‐Woo Son
Byung‐Su Yoo
author_facet Dong‐Hyuk Cho
Jimi Choi
Jong‐Chan Youn
Mi‐Na Kim
Chan Joo Lee
Jung‐Woo Son
Byung‐Su Yoo
author_sort Dong‐Hyuk Cho
collection DOAJ
description Abstract Aims Whether medication adherence to angiotensin receptor‐neprilysin inhibitor (ARNI) in real‐world practice is associated with the reduced risk of all‐cause mortality or hospitalization relative to that with traditional renin–angiotensin system (RAS) blockade remains unclear. This study investigated the influence of medication adherence of ARNI and traditional RAS blockade in heart failure with reduced ejection fraction (HFrEF). Method We conducted a nationwide longitudinal cohort study with patients with HFrEF using data from the Korean National Health Insurance Service data (2017–2021) covering the entire population. A total of 13 483 patients with HFrEF who received ARNI were matched 1:1 with 13 483 patients who received traditional RAS blockade using propensity score matching. The primary outcome was a composite of all‐cause mortality or any hospitalization within one year. Medication adherence was assessed by calculating the proportion of days covered (PDC) relative to total medication prescribed. ARNI and traditional RAS blockade adherence rates were directly compared to analyse their respective associations with the primary outcome. Results Patients in the ARNI group had a lower rate of the primary outcome than those in the traditional RAS blockade group [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.75–0.81; P < 0.001]. Mean PDC values spanning 1 year were 92.6 ± 14.5% and 90.9 ± 17.7% in the ARNI and RAS blockade groups, respectively (P < 0.001). Among patients with PDC ≥ 80%, the risk of primary outcome was significantly lower in the ARNI group than in the RAS blockade group (HR 0.75; 95% CI 0.72–0.78; P < 0.001) while a risk reduction with ARNI was not observed among patients with PDC < 80% (HR 0.95; 95% CI 0.85–1.05; P = 0.313). The beneficial effect was more pronounced among patients with PDC ≥ 80% than that among patients with PDC < 80% (P for interaction <0.001). Conclusions In a real‐world cohort with HFrEF, ARNI was superior to traditional RAS blockade in reducing the risk of all‐cause mortality and hospitalization. The benefit of ARNI was pronounced among patients with high medication adherence but not among those with low medication adherence, highlighting the importance of adherence to ARNI treatment for HFrEF. Trial Registration PARADE‐HF ClinicalTrials.gov number, NCT05329727.
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spelling doaj-art-202bc59bfc724b4bbe0eb38e95f115f72025-08-20T02:16:22ZengWileyESC Heart Failure2055-58222025-02-0112160361210.1002/ehf2.15117Angiotensin receptor‐neprilysin inhibitor adherence and outcomes in heart failure with reduced ejection fractionDong‐Hyuk Cho0Jimi Choi1Jong‐Chan Youn2Mi‐Na Kim3Chan Joo Lee4Jung‐Woo Son5Byung‐Su Yoo6Division of Cardiology, Department of Internal Medicine Korea University Anam Hospital, Korea University College of Medicine Seoul South KoreaDivision of Endocrinology and Metabolism, Department of Internal Medicine Korea University Anam Hospital, Korea University College of Medicine Seoul South KoreaDivision of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, Catholic Research Institute for Intractable Cardiovascular Disease, College of Medicine Catholic University of Korea Seoul South KoreaDivision of Cardiology, Department of Internal Medicine Korea University Anam Hospital, Korea University College of Medicine Seoul South KoreaDivision of Cardiology, Department of Internal Medicine, Severance Hospital Yonsei University College of Medicine Seoul South KoreaDivision of Cardiology, Department of Internal Medicine, Yonsei University Wonju College of Medicine Wonju South KoreaDivision of Cardiology, Department of Internal Medicine, Yonsei University Wonju College of Medicine Wonju South KoreaAbstract Aims Whether medication adherence to angiotensin receptor‐neprilysin inhibitor (ARNI) in real‐world practice is associated with the reduced risk of all‐cause mortality or hospitalization relative to that with traditional renin–angiotensin system (RAS) blockade remains unclear. This study investigated the influence of medication adherence of ARNI and traditional RAS blockade in heart failure with reduced ejection fraction (HFrEF). Method We conducted a nationwide longitudinal cohort study with patients with HFrEF using data from the Korean National Health Insurance Service data (2017–2021) covering the entire population. A total of 13 483 patients with HFrEF who received ARNI were matched 1:1 with 13 483 patients who received traditional RAS blockade using propensity score matching. The primary outcome was a composite of all‐cause mortality or any hospitalization within one year. Medication adherence was assessed by calculating the proportion of days covered (PDC) relative to total medication prescribed. ARNI and traditional RAS blockade adherence rates were directly compared to analyse their respective associations with the primary outcome. Results Patients in the ARNI group had a lower rate of the primary outcome than those in the traditional RAS blockade group [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.75–0.81; P < 0.001]. Mean PDC values spanning 1 year were 92.6 ± 14.5% and 90.9 ± 17.7% in the ARNI and RAS blockade groups, respectively (P < 0.001). Among patients with PDC ≥ 80%, the risk of primary outcome was significantly lower in the ARNI group than in the RAS blockade group (HR 0.75; 95% CI 0.72–0.78; P < 0.001) while a risk reduction with ARNI was not observed among patients with PDC < 80% (HR 0.95; 95% CI 0.85–1.05; P = 0.313). The beneficial effect was more pronounced among patients with PDC ≥ 80% than that among patients with PDC < 80% (P for interaction <0.001). Conclusions In a real‐world cohort with HFrEF, ARNI was superior to traditional RAS blockade in reducing the risk of all‐cause mortality and hospitalization. The benefit of ARNI was pronounced among patients with high medication adherence but not among those with low medication adherence, highlighting the importance of adherence to ARNI treatment for HFrEF. Trial Registration PARADE‐HF ClinicalTrials.gov number, NCT05329727.https://doi.org/10.1002/ehf2.15117angiotensin receptor‐neprilysin inhibitormedication adherencerenin–angiotensin system blockadereal‐world evidence
spellingShingle Dong‐Hyuk Cho
Jimi Choi
Jong‐Chan Youn
Mi‐Na Kim
Chan Joo Lee
Jung‐Woo Son
Byung‐Su Yoo
Angiotensin receptor‐neprilysin inhibitor adherence and outcomes in heart failure with reduced ejection fraction
ESC Heart Failure
angiotensin receptor‐neprilysin inhibitor
medication adherence
renin–angiotensin system blockade
real‐world evidence
title Angiotensin receptor‐neprilysin inhibitor adherence and outcomes in heart failure with reduced ejection fraction
title_full Angiotensin receptor‐neprilysin inhibitor adherence and outcomes in heart failure with reduced ejection fraction
title_fullStr Angiotensin receptor‐neprilysin inhibitor adherence and outcomes in heart failure with reduced ejection fraction
title_full_unstemmed Angiotensin receptor‐neprilysin inhibitor adherence and outcomes in heart failure with reduced ejection fraction
title_short Angiotensin receptor‐neprilysin inhibitor adherence and outcomes in heart failure with reduced ejection fraction
title_sort angiotensin receptor neprilysin inhibitor adherence and outcomes in heart failure with reduced ejection fraction
topic angiotensin receptor‐neprilysin inhibitor
medication adherence
renin–angiotensin system blockade
real‐world evidence
url https://doi.org/10.1002/ehf2.15117
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