Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Aug 5;3(9):101126.
doi: 10.1016/j.jacadv.2024.101126. eCollection 2024 Sep.

Polypharmacy and Guideline-Directed Medical Therapy Initiation Among Adults Hospitalized With Heart Failure

Chukwuma Onyebeke  1 , David Zhang  1 , Mahad Musse  2 , Ozan Unlu  3 , Musarrat Nahid  1 , Andrew P Ambrosy  4 , Emily B Levitan  5 , Monika M Safford  1 , Parag Goyal  1   2
Affiliations

Polypharmacy and Guideline-Directed Medical Therapy Initiation Among Adults Hospitalized With Heart Failure

Chukwuma Onyebeke et al. JACC Adv. .

Abstract

Background: Underprescribing of guideline-directed medical therapy (GDMT) for heart failure (HF) persists.

Objectives: The purpose of this study was to assess polypharmacy as a barrier to GDMT.

Methods: We examined participants hospitalized for HF with reduced ejection fraction and HF with mildly reduced ejection fraction between 2003 and 2017 from the Reasons for Geographic and Racial Differences in Stroke study. Participants were stratified by admission medication count-0 to 4, 5 to 9, and ≥10 medications. We examined GDMT use at admission, GDMT contraindications, and initiation of eligible indicated GDMT by medication count. We conducted a multivariable Poisson regression with robust standard errors to examine the association between medication count and GDMT initiation. GDMT included agents for HF with reduced ejection fraction/HF with mildly reduced ejection fraction, antiplatelet agents and statins for coronary artery disease, and anticoagulants for atrial fibrillation.

Results: Among 545 participants with HF, 34% were not taking a beta-blocker, 39% were not taking an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, or hydralazine-isosorbide dinitrate, and 90% were not taking a mineralocorticoid receptor antagonist at admission; among participants with coronary artery disease, 36% were not taking an antiplatelet agent, and 38% were not taking a statin; and among participants with atrial fibrillation, 49% were not taking an anticoagulant. Polypharmacy was inversely associated with initiation of at least one indicated medication (5-9 medications: relative risk [RR]: 0.67; 95% CI: 0.56-0.82; P < 0.001; ≥10 medications: RR: 0.50; 95% CI: 0.39-0.64; P < 0.001) and initiation of at least half of indicated medications (5-9 medications: RR: 0.64; 95% CI: 0.51-0.81; P < 0.001; ≥10 medications: RR: 0.50; 95% CI: 0.38-0.67; P < 0.001).

Conclusions: Polypharmacy is an important barrier to GDMT.

Keywords: guideline-directed medical therapy; heart failure.

PubMed Disclaimer

Conflict of interest statement

This research project is supported by cooperative agreement U01 NS041588, co-funded by the 10.13039/100000065National Institute of Neurological Disorders and Stroke (NINDS) and the 10.13039/100000049National Institute on Aging (NIA), the 10.13039/100000002National Institutes of Health, and the 10.13039/100000016Department of Health and Human Services. Additional funding was provided by 10.13039/100000050National Heart, Lung, and Blood Institute (NHLBI) grant R01HL080477 (Dr Safford) and 10.13039/100000049NIA grant R03AG056446 (Dr Goyal). Representatives from the 10.13039/100000050NHLBI did not have any role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, or the preparation or approval of the manuscript. Dr Goyal is supported by 10.13039/100000968American Heart Association grant 20CDA35310455, 10.13039/100000049National Institute on Aging grant K76AG064428; has received personal fees for medicolegal consulting related to heart failure; has received consulting fees from Sensorum Health; and has received honoraria from Akcea Therapeutics, Inc. Dr Ambrosy is supported by a Mentored Patient-Oriented Research Career Development Award (K23HL150159) through the 10.13039/100000050National Heart, Lung, and Blood Institute and has received relevant research support through grants to his institution from 10.13039/100000046Abbott, 10.13039/100014389Amarin Pharma, 10.13039/100006520Edwards Lifesciences, 10.13039/501100022336Esperion, Lexicon, and 10.13039/100008272Novartis. Dr Levitan has received research funding from 10.13039/100002429Amgen, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Central Illustration
Central Illustration
Polypharmacy and Initiation of GDMT The majority of participants admitted for HFrEF/HFmEF within the REGARDS cohort had either polypharmacy (5-9 medications) or hyperpolypharmacy (≥10 medications) at hospital admission. The percent of participants initiated on each eligible GDMT medication was lower among participants with polypharmacy and hyperpolypharmacy compared to those without polypharmacy. ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; ARNI = angiotensin receptor-neprilysin inhibitor; CAD = coronary artery disease; GDMT = guideline-directed medical therapy; HFmrEF = heart failure with mildly reduced ejection fraction; HFrEF = heart failure with reduced ejection fraction; HYD-ISD = hydralazine-isosorbide dinitrate; REGARDS = Reasons for Geographic and Racial Disparities in Stroke.
Figure 1
Figure 1
Proportion of Participants Initiated on Any, at Least Half, and All Medications When Indicated and Eligible for Initiation, Stratified by Medication Count The proportion of participants started on at least one, at least 50%, and all of indicated medications decreased with an increasing medication count at admission. Error bars indicate standard error.
Figure 2
Figure 2
Proportion of Participants Initiated on Each Medication When Indicated and Eligible for Initiation, Stratified by Medication Count The proportion of participants with initiation of indicated beta-blockers, ACEI/ARB/ARNI/HYD-ISD, and anticoagulants decreased with an increasing medication count at admission. The proportion of participants with initiation of MRA, antiplatelet agents, and statins were highest for those who took 0 to 4 medications at admission and lower for those who took 5 to 9 and ≥10 medications at admission. Error bars indicate standard error. ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; ARNI = angiotensin receptor-neprilysin inhibitor; HYD-ISD = hydralazine-isosorbide dinitrate; MRA = mineralocorticoid receptor antagonist.
Figure 3
Figure 3
Relative Risk of Initiation of Any, at Least Half, and All Medications According to Medication Burden A multivariable-adjusted Poisson regression with robust standard errors estimating the relative risk (RR) and 95% CIs showed that taking 5 to 9 and ≥10 medications at the time of admission were inversely associated with initiation of at least one indicated medication and inversely associated with initiation of ≥50% of indicated medications. There was also a signal for an association between taking 5 to 9 and ≥10 medications at the time of admission and initiation of all indicated medications, but this did not meet statistical significance.
See this image and copyright information in PMC

References

    1. Heidenreich P.A., Bozkurt B., Aguilar D., et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American heart association Joint committee on clinical practice guidelines. Circulation. 2022;145(18):E895–E1032. - PubMed
    1. Greene S.J., Butler J., Albert N.M., et al. Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF registry. J Am Coll Cardiol. 2018;72(4):351–366. - PubMed
    1. Krantz M.J., Ambardekar A.V., Kaltenbach L., Hernandez A.F., Heidenreich P.A., Fonarow G.C. Patterns and Predictors of evidence-based medication Continuation among hospitalized heart failure patients (from Get with the guidelines–heart failure) Am J Cardiol. 2011;107(12):1818–1823. - PubMed
    1. 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. 2022;400(10367):1938–1952. - PubMed
    1. Bermingham M., Shanahan M.K., O’Connell E., et al. Aspirin use in heart failure: is low-dose therapy associated with mortality and morbidity benefits in a large community population? Circ Heart Fail. 2014;7(2):243–250. - PubMed

LinkOut - more resources