Adherence and Discontinuation of Optimal Heart Failure Therapies According to Age: A Danish Nationwide Study

Caroline H. Garred; Deewa Zahir; Jawad H. Butt; Pauline B. Ravn; Jonas Bruhn; Gunnar H. Gislason; Emil L. Fosbøl; Christian Torp-Pedersen; Mark C. Petrie; John J.V. McMurray; Lars Køber; Morten Schou

doi:10.1161/JAHA.122.026187

Adherence and Discontinuation of Optimal Heart Failure Therapies According to Age: A Danish Nationwide Study

Caroline H. Garred^*, Deewa Zahir, Jawad H. Butt, Pauline B. Ravn, Jonas Bruhn, Gunnar H. Gislason, Emil L. Fosbøl, Christian Torp-Pedersen, Mark C. Petrie, John J.V. McMurray, Lars Køber, Morten Schou

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

BACKGROUND: Guideline-recommended disease-modifying pharmacological therapies for heart failure (HF) with reduced ejection fraction are underutilized, particularly among elderly patients. We studied the association of age in adherence and discontinuation of angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers (ACEi/ARB), β-blockers (BB), and mineralocorticoid receptor antagonists. METHODS AND RESULTS: Patients with a first heart failure diagnosis who had initiated ACEi/ARB and BB within 120 days of presentation were included from nationwide registries and divided into 3 age groups: <65 years (reference), 65 to 79, and ≥80. One-year median proportions of daily target doses were calculated. Adherence was estimated by the proportion of days covered. The 5-year risk of discontinuation was assessed with the Aalen-Johansen estimator. Discontinuation rates were evaluated using Multivariable Cox regression. Twenty-nine thousand four hundred eighty-two patients were included. Advancing age was associated with lower median proportions of daily target doses and adherence (ACEi/ARB 79.1%, 77.5%, and 69.4%; BB 79.1%, 78.6%, and 73.8%), in the <65, 65 to 79, and ≥80 age groups, respectively. Age ≥80 was associated with higher discontinuation rates (cumulative incidence, ACEi/ARB 41%, 44%, and 51%; BB 38%, 35%, and 39%; hazard ratio, ACEi/ARB 1.60 [95% CI, 1.51–1.69]; BB 1.33 [95% CI, 1.25–1.41]). The risk of mineralocorticoid receptor antagonists discontinuation differed little with age (50%, 54%, and 56%), although mineralocorticoid receptor antagonists initiation in the most elderly was less frequent (33%, 33%, and 22%). CONCLUSIONS: In a nationwide cohort of patients with heart failure, advanced age was associated with lower proportions of daily target doses, lower adherence, and higher discontinuation rates of ACEi/ARB and BBs. Focus on treatment adherence and optimal dosages among elderly patients with heart failure could improve outcomes.

Original language	English
Article number	e026187
Journal	Journal of the American Heart Association
Volume	11
Issue number	19
Number of pages	19
ISSN	2047-9980
DOIs	https://doi.org/10.1161/JAHA.122.026187
Publication status	Published - 2022

Bibliographical note

Funding Information:
Garred reports lecture fees from Astra Zeneca. Dr Butt reports advisory board honoraria from Bayer, outside the submitted work. Dr Petri and Dr McMurray are supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217). Dr Schou reports lecture fees from Novartis, Astra Zeneca, Novo Nordisk, and Boehringer Ingelheim.

Keywords

adherence
age
discontinuation
heart failure
pharmacotherapy

Access to Document

10.1161/JAHA.122.026187

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Cite this

Garred, C. H., Zahir, D., Butt, J. H., Ravn, P. B., Bruhn, J., Gislason, G. H., Fosbøl, E. L., Torp-Pedersen, C., Petrie, M. C., McMurray, J. J. V., Køber, L., & Schou, M. (2022). Adherence and Discontinuation of Optimal Heart Failure Therapies According to Age: A Danish Nationwide Study. Journal of the American Heart Association, 11(19), Article e026187. https://doi.org/10.1161/JAHA.122.026187

Garred, CH, Zahir, D, Butt, JH, Ravn, PB, Bruhn, J, Gislason, GH, Fosbøl, EL, Torp-Pedersen, C, Petrie, MC, McMurray, JJV, Køber, L & Schou, M 2022, 'Adherence and Discontinuation of Optimal Heart Failure Therapies According to Age: A Danish Nationwide Study', Journal of the American Heart Association, vol. 11, no. 19, e026187. https://doi.org/10.1161/JAHA.122.026187

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title = "Adherence and Discontinuation of Optimal Heart Failure Therapies According to Age: A Danish Nationwide Study",

abstract = "BACKGROUND: Guideline-recommended disease-modifying pharmacological therapies for heart failure (HF) with reduced ejection fraction are underutilized, particularly among elderly patients. We studied the association of age in adherence and discontinuation of angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers (ACEi/ARB), β-blockers (BB), and mineralocorticoid receptor antagonists. METHODS AND RESULTS: Patients with a first heart failure diagnosis who had initiated ACEi/ARB and BB within 120 days of presentation were included from nationwide registries and divided into 3 age groups: <65 years (reference), 65 to 79, and ≥80. One-year median proportions of daily target doses were calculated. Adherence was estimated by the proportion of days covered. The 5-year risk of discontinuation was assessed with the Aalen-Johansen estimator. Discontinuation rates were evaluated using Multivariable Cox regression. Twenty-nine thousand four hundred eighty-two patients were included. Advancing age was associated with lower median proportions of daily target doses and adherence (ACEi/ARB 79.1%, 77.5%, and 69.4%; BB 79.1%, 78.6%, and 73.8%), in the <65, 65 to 79, and ≥80 age groups, respectively. Age ≥80 was associated with higher discontinuation rates (cumulative incidence, ACEi/ARB 41%, 44%, and 51%; BB 38%, 35%, and 39%; hazard ratio, ACEi/ARB 1.60 [95% CI, 1.51–1.69]; BB 1.33 [95% CI, 1.25–1.41]). The risk of mineralocorticoid receptor antagonists discontinuation differed little with age (50%, 54%, and 56%), although mineralocorticoid receptor antagonists initiation in the most elderly was less frequent (33%, 33%, and 22%). CONCLUSIONS: In a nationwide cohort of patients with heart failure, advanced age was associated with lower proportions of daily target doses, lower adherence, and higher discontinuation rates of ACEi/ARB and BBs. Focus on treatment adherence and optimal dosages among elderly patients with heart failure could improve outcomes.",

keywords = "adherence, age, discontinuation, heart failure, pharmacotherapy",

author = "Garred, {Caroline H.} and Deewa Zahir and Butt, {Jawad H.} and Ravn, {Pauline B.} and Jonas Bruhn and Gislason, {Gunnar H.} and Fosb{\o}l, {Emil L.} and Christian Torp-Pedersen and Petrie, {Mark C.} and McMurray, {John J.V.} and Lars K{\o}ber and Morten Schou",

note = "Funding Information: Garred reports lecture fees from Astra Zeneca. Dr Butt reports advisory board honoraria from Bayer, outside the submitted work. Dr Petri and Dr McMurray are supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217). Dr Schou reports lecture fees from Novartis, Astra Zeneca, Novo Nordisk, and Boehringer Ingelheim. ",

year = "2022",

doi = "10.1161/JAHA.122.026187",

language = "English",

volume = "11",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "Wiley-Blackwell",

number = "19",

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TY - JOUR

T1 - Adherence and Discontinuation of Optimal Heart Failure Therapies According to Age

T2 - A Danish Nationwide Study

AU - Garred, Caroline H.

AU - Zahir, Deewa

AU - Butt, Jawad H.

AU - Ravn, Pauline B.

AU - Bruhn, Jonas

AU - Gislason, Gunnar H.

AU - Fosbøl, Emil L.

AU - Torp-Pedersen, Christian

AU - Petrie, Mark C.

AU - McMurray, John J.V.

AU - Køber, Lars

AU - Schou, Morten

N1 - Funding Information: Garred reports lecture fees from Astra Zeneca. Dr Butt reports advisory board honoraria from Bayer, outside the submitted work. Dr Petri and Dr McMurray are supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217). Dr Schou reports lecture fees from Novartis, Astra Zeneca, Novo Nordisk, and Boehringer Ingelheim.

PY - 2022

Y1 - 2022

N2 - BACKGROUND: Guideline-recommended disease-modifying pharmacological therapies for heart failure (HF) with reduced ejection fraction are underutilized, particularly among elderly patients. We studied the association of age in adherence and discontinuation of angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers (ACEi/ARB), β-blockers (BB), and mineralocorticoid receptor antagonists. METHODS AND RESULTS: Patients with a first heart failure diagnosis who had initiated ACEi/ARB and BB within 120 days of presentation were included from nationwide registries and divided into 3 age groups: <65 years (reference), 65 to 79, and ≥80. One-year median proportions of daily target doses were calculated. Adherence was estimated by the proportion of days covered. The 5-year risk of discontinuation was assessed with the Aalen-Johansen estimator. Discontinuation rates were evaluated using Multivariable Cox regression. Twenty-nine thousand four hundred eighty-two patients were included. Advancing age was associated with lower median proportions of daily target doses and adherence (ACEi/ARB 79.1%, 77.5%, and 69.4%; BB 79.1%, 78.6%, and 73.8%), in the <65, 65 to 79, and ≥80 age groups, respectively. Age ≥80 was associated with higher discontinuation rates (cumulative incidence, ACEi/ARB 41%, 44%, and 51%; BB 38%, 35%, and 39%; hazard ratio, ACEi/ARB 1.60 [95% CI, 1.51–1.69]; BB 1.33 [95% CI, 1.25–1.41]). The risk of mineralocorticoid receptor antagonists discontinuation differed little with age (50%, 54%, and 56%), although mineralocorticoid receptor antagonists initiation in the most elderly was less frequent (33%, 33%, and 22%). CONCLUSIONS: In a nationwide cohort of patients with heart failure, advanced age was associated with lower proportions of daily target doses, lower adherence, and higher discontinuation rates of ACEi/ARB and BBs. Focus on treatment adherence and optimal dosages among elderly patients with heart failure could improve outcomes.

AB - BACKGROUND: Guideline-recommended disease-modifying pharmacological therapies for heart failure (HF) with reduced ejection fraction are underutilized, particularly among elderly patients. We studied the association of age in adherence and discontinuation of angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers (ACEi/ARB), β-blockers (BB), and mineralocorticoid receptor antagonists. METHODS AND RESULTS: Patients with a first heart failure diagnosis who had initiated ACEi/ARB and BB within 120 days of presentation were included from nationwide registries and divided into 3 age groups: <65 years (reference), 65 to 79, and ≥80. One-year median proportions of daily target doses were calculated. Adherence was estimated by the proportion of days covered. The 5-year risk of discontinuation was assessed with the Aalen-Johansen estimator. Discontinuation rates were evaluated using Multivariable Cox regression. Twenty-nine thousand four hundred eighty-two patients were included. Advancing age was associated with lower median proportions of daily target doses and adherence (ACEi/ARB 79.1%, 77.5%, and 69.4%; BB 79.1%, 78.6%, and 73.8%), in the <65, 65 to 79, and ≥80 age groups, respectively. Age ≥80 was associated with higher discontinuation rates (cumulative incidence, ACEi/ARB 41%, 44%, and 51%; BB 38%, 35%, and 39%; hazard ratio, ACEi/ARB 1.60 [95% CI, 1.51–1.69]; BB 1.33 [95% CI, 1.25–1.41]). The risk of mineralocorticoid receptor antagonists discontinuation differed little with age (50%, 54%, and 56%), although mineralocorticoid receptor antagonists initiation in the most elderly was less frequent (33%, 33%, and 22%). CONCLUSIONS: In a nationwide cohort of patients with heart failure, advanced age was associated with lower proportions of daily target doses, lower adherence, and higher discontinuation rates of ACEi/ARB and BBs. Focus on treatment adherence and optimal dosages among elderly patients with heart failure could improve outcomes.

KW - adherence

KW - age

KW - discontinuation

KW - heart failure

KW - pharmacotherapy

U2 - 10.1161/JAHA.122.026187

DO - 10.1161/JAHA.122.026187

M3 - Journal article

C2 - 36172925

AN - SCOPUS:85139442051

SN - 2047-9980

VL - 11

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 19

M1 - e026187

ER -