Digoxin Discontinuation in Patients With HFrEF on Beta-Blockers: Implication for Future 'Knock-Out Trials' in Heart Failure

被引：0

作者：

Lam, Phillip H. ^{[1
,2
,3
]}

Liu, Kevin ^{[1
,2
]}

Ahmed, Amiya A. ^{[4
,5
]}

Butler, Javed ^{[6
,7
]}

Heidenreich, Paul A. ^{[8
,9
]}

Anker, Markus S. ^{[10
]}

Faselis, Charles ^{[1
,11
]}

Deedwania, Prakash ^{[12
]}

Aronow, Wilbert S. ^{[13
,14
]}

Kanonidis, Ioannis ^{[15
]}

Masson, Ravi ^{[16
]}

Gill, Gauravpal S. ^{[17
]}

Morgan, Charity J. ^{[18
]}

Arundel, Cherinne ^{[1
,2
,11
]}

Allman, Richard M. ^{[11
,18
,19
]}

Wu, Wen-Chih ^{[20
,21
]}

Fonarow, Gregg C. ^{[22
]}

Ahmed, Ali ^{[1
,2
,11
]}

机构：

[1] Vet Affairs Med Ctr, Washington, DC USA

[2] Georgetown Univ, Washington, DC USA

[3] Medstar Washington Hosp Ctr, Washington, DC USA

[4] Yale Univ, New Haven, CT USA

[5] Vet Affairs Med Ctr, West Haven, CT USA

[6] Baylor Scott & White Res Inst, Dallas, TX USA

[7] Univ Mississippi, Jackson, MS USA

[8] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA

[9] Stanford Univ, Sch Med, Stanford, CA USA

[10] Charite Univ Med Berlin, Berlin, Germany

[11] George Washington Univ, Washington, DC USA

[12] Univ Calif San Francisco, San Francisco, CA USA

[13] Westchester Med Ctr, Valhalla, NY USA

[14] New York Med Coll, Valhalla, NY USA

[15] Aristotelian Univ, Thessaloniki, Greece

[16] Loma Linda Univ, Loma Linda, CA USA

[17] James River Cardiol, Colonial Hts, VA 23834 USA

[18] Univ Alabama Birmingham, Birmingham, AL USA

[19] Wake Forest Univ, Winston Salem, NC USA

[20] Vet Affairs Med Ctr, Providence, RI USA

[21] Brown Univ, Providence, RI USA

[22] Univ Calif Los Angeles, Los Angeles, CA USA

来源：

AMERICAN JOURNAL OF MEDICINE | 2025年 / 138卷 / 03期

基金：

美国国家卫生研究院;

关键词：

Beta-blockers; Digoxin; Discontinuation; Heart failure; HFrEF; SYSTOLIC BLOOD-PRESSURE; PROPENSITY-SCORE; OPTIMIZE-HF; OUTCOMES; WITHDRAWAL; MORTALITY; THERAPY; DEATH; MODE;

D O I：

10.1016/j.amjmed.2024.10.015

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND: National heart failure guidelines recommend quadruple therapy with renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors for patients with heart failure with reduced ejection fraction (HFrEF), most of whom also receive loop diuretics. However, the guidelines are less clear about the safe approaches to discontinuing older drugs whose decreasing or residual benefit is less well understood. The objective of this study was to examine whether digoxin can be safely discontinued in patients with HFrEF receiving beta-blockers. METHODS: In OPTIMIZE-HF, of 2477 patients with HFrEF (EF <= 45%) receiving beta-blockers and digoxin, digoxin was discontinued in 450 patients. We assembled a propensity score-matched cohort of 433 pairs of patients in which digoxin continuation vs. discontinuation groups were balanced on 51 baseline characteristics. Using the same approach, from 992 patients not on beta-blockers, we assembled a matched cohort of 198 pairs of patients also balanced on 51 baseline characteristics. Hazard ratios (HRs) and 95% CIs for 1-year outcomes were estimated. RESULTS: Among patients receiving beta-blockers, digoxin discontinuation had no association with the combined endpoint of heart failure readmission or death (HR, 1.01; 95% CI, 0.85-1.19), heart failure readmission (HR, 1.03; 95% CI, 0.85-1.25) or death (HR, 0.91; 95% CI, 0.72-1.14). Respective HRs (95% CIs) among patients not receiving beta-blockers were 1.60 (1.25-2.04), 1.62 (1.18-2.22) and 1.43 (1.08-1.89). CONCLUSIONS: Digoxin can be discontinued without increasing the risk of adverse outcomes in patients with HFrEF receiving beta-blockers. Future studies need to examine the residual benefit of older heart failure drugs to ensure their safe discontinuation in patients with HFrEF receiving newer guideline-directed medical therapy. Published by Elsevier Inc. center dot The American Journal of Medicine (2025) 138:495-503

引用

页码：495 / 503.e1

页数：10

共 39 条

[1] McDonagh T.A., Metra M., Adamo M., Et al., 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, Eur Heart J, 42, pp. 3599-3726, (2021)
[2] Heidenreich P.A., Bozkurt B., Aguilar D., Et al., 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines, J Am Coll Cardiol, 79, pp. 1757-1780, (2022)
[3] Greene S.J., Ayodele I., Pierce J.B., Et al., Eligibility and projected benefits of rapid initiation of quadruple therapy for newly diagnosed heart failure, JACC Heart Fail, 12, pp. 1365-1377, (2024)
[4] Mebazaa A., Davison B., Chioncel O., Et al., Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial, Lancet, 400, pp. 1938-1952, (2022)
[5] Sukumar S., Orkaby A.R., Schwartz J.B., Et al., Polypharmacy in older heart failure patients: a multidisciplinary approach, Curr Heart Fail Rep, 19, pp. 290-302, (2022)
[6] Stefil M., Dixon M., Bahar J., Et al., Polypharmacy in older people with heart failure: roles of the geriatrician and pharmacist, Card Fail Rev, 8, (2022)
[7] Khezrian M., McNeil C.J., Murray A.D., Myint P.K., An overview of prevalence, determinants and health outcomes of polypharmacy, Ther Adv Drug Saf, 11, (2020)
[8] Chang T.I., Park H., Kim D.W., Et al., Polypharmacy, hospitalization, and mortality risk: a nationwide cohort study, Sci Rep, 10, (2020)
[9] Wang X., Liu K., Shirai K., Et al., Prevalence and trends of polypharmacy in U.S. adults, 1999-2018, Glob Health Res Policy, 8, (2023)
[10] The effect of digoxin on mortality and morbidity in patients with heart failure, N Engl J Med, 336, pp. 525-533, (1997)

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