Polypharmacy and Optimization of Guideline-Directed Medical Therapy in Heart Failure: The GUIDE-IT Trial

Muhammad Shahzeb Khan; Sumitabh Singh; Matthew W. Segar; Muhammad Shariq Usman; Neil Keshvani; Andrew P. Ambrosy; Mona Fiuzat; Harriette G.C. Van Spall; Gregg C. Fonarow; Faiez Zannad; G. Michael Felker; James L. Januzzi; Christopher O'Connor; Javed Butler; Ambarish Pandey

doi:10.1016/j.jchf.2023.03.007

Polypharmacy and Optimization of Guideline-Directed Medical Therapy in Heart Failure: The GUIDE-IT Trial

Muhammad Shahzeb Khan, Sumitabh Singh, Matthew W. Segar, Muhammad Shariq Usman, Neil Keshvani, Andrew P. Ambrosy, Mona Fiuzat, Harriette G.C. Van Spall, Gregg C. Fonarow, Faiez Zannad, G. Michael Felker, James L. Januzzi, Christopher O'Connor, Javed Butler, Ambarish Pandey

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Background: Polypharmacy is common among patients with heart failure with reduced ejection fraction (HFrEF). However, its impact on the use of optimal guideline-directed medical therapy (GDMT) is not well established. Objectives: This study sought to evaluate the association between polypharmacy and odds of receiving optimal GDMT over time among patients with HFrEF. Methods: The authors conducted a post hoc analysis of the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial. Polypharmacy was defined as receiving ≥5 medications (excluding HFrEF GDMT) at baseline. The outcome of interest was optimal triple therapy GDMT (concurrent administration of a renin-angiotensin-aldosterone blocker and beta-blocker at 50% of the target dose and a mineralocorticoid receptor antagonist at any dose) achieved over the 12-month follow-up. Multivariable adjusted mixed-effect logistic regression models with multiplicative interaction terms (time × polypharmacy) were constructed to evaluate how polypharmacy at baseline modified the odds of achieving optimal GDMT on follow-up. Results: The study included 891 participants with HFrEF. The median number of non-GDMT medications at baseline was 4 (IQR: 3-6), with 414 (46.5%) prescribed ≥5 and identified as being on polypharmacy. The proportion of participants who achieved optimal GDMT at the end of the 12-month follow-up was lower with vs without polypharmacy at baseline (15% vs 19%, respectively). In adjusted mixed models, the odds of achieving optimal GDMT over time were modified by baseline polypharmacy status (P for interaction < 0.001). Patients without polypharmacy at baseline had increased odds of achieving GDMT (OR: 1.16 [95% CI: 1.12-1.21] per 1-month increase; P < 0.001) but not patients with polypharmacy (OR: 1.01 [95% CI: 0.96-1.06)] per 1-month increase). Conclusions: Patients with HFrEF who are on non-GDMT polypharmacy have lower odds of achieving optimal GDMT on follow-up.

Original language	English (US)
Pages (from-to)	1507-1517
Number of pages	11
Journal	JACC: Heart Failure
Volume	11
Issue number	11
DOIs	https://doi.org/10.1016/j.jchf.2023.03.007
State	Published - Nov 2023

Keywords

GDMT
heart failure with reduced ejection fraction (HFrEF)
polypharmacy
triple therapy

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jchf.2023.03.007

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Khan, M. S., Singh, S., Segar, M. W., Usman, M. S., Keshvani, N., Ambrosy, A. P., Fiuzat, M., Van Spall, H. G. C., Fonarow, G. C., Zannad, F., Felker, G. M., Januzzi, J. L., O'Connor, C., Butler, J., & Pandey, A. (2023). Polypharmacy and Optimization of Guideline-Directed Medical Therapy in Heart Failure: The GUIDE-IT Trial. JACC: Heart Failure, 11(11), 1507-1517. https://doi.org/10.1016/j.jchf.2023.03.007

Khan, MS, Singh, S, Segar, MW, Usman, MS, Keshvani, N, Ambrosy, AP, Fiuzat, M, Van Spall, HGC, Fonarow, GC, Zannad, F, Felker, GM, Januzzi, JL, O'Connor, C, Butler, J & Pandey, A 2023, 'Polypharmacy and Optimization of Guideline-Directed Medical Therapy in Heart Failure: The GUIDE-IT Trial', JACC: Heart Failure, vol. 11, no. 11, pp. 1507-1517. https://doi.org/10.1016/j.jchf.2023.03.007

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title = "Polypharmacy and Optimization of Guideline-Directed Medical Therapy in Heart Failure: The GUIDE-IT Trial",

abstract = "Background: Polypharmacy is common among patients with heart failure with reduced ejection fraction (HFrEF). However, its impact on the use of optimal guideline-directed medical therapy (GDMT) is not well established. Objectives: This study sought to evaluate the association between polypharmacy and odds of receiving optimal GDMT over time among patients with HFrEF. Methods: The authors conducted a post hoc analysis of the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial. Polypharmacy was defined as receiving ≥5 medications (excluding HFrEF GDMT) at baseline. The outcome of interest was optimal triple therapy GDMT (concurrent administration of a renin-angiotensin-aldosterone blocker and beta-blocker at 50% of the target dose and a mineralocorticoid receptor antagonist at any dose) achieved over the 12-month follow-up. Multivariable adjusted mixed-effect logistic regression models with multiplicative interaction terms (time × polypharmacy) were constructed to evaluate how polypharmacy at baseline modified the odds of achieving optimal GDMT on follow-up. Results: The study included 891 participants with HFrEF. The median number of non-GDMT medications at baseline was 4 (IQR: 3-6), with 414 (46.5%) prescribed ≥5 and identified as being on polypharmacy. The proportion of participants who achieved optimal GDMT at the end of the 12-month follow-up was lower with vs without polypharmacy at baseline (15% vs 19%, respectively). In adjusted mixed models, the odds of achieving optimal GDMT over time were modified by baseline polypharmacy status (P for interaction < 0.001). Patients without polypharmacy at baseline had increased odds of achieving GDMT (OR: 1.16 [95% CI: 1.12-1.21] per 1-month increase; P < 0.001) but not patients with polypharmacy (OR: 1.01 [95% CI: 0.96-1.06)] per 1-month increase). Conclusions: Patients with HFrEF who are on non-GDMT polypharmacy have lower odds of achieving optimal GDMT on follow-up.",

keywords = "GDMT, heart failure with reduced ejection fraction (HFrEF), polypharmacy, triple therapy",

author = "Khan, {Muhammad Shahzeb} and Sumitabh Singh and Segar, {Matthew W.} and Usman, {Muhammad Shariq} and Neil Keshvani and Ambrosy, {Andrew P.} and Mona Fiuzat and {Van Spall}, {Harriette G.C.} and Fonarow, {Gregg C.} and Faiez Zannad and Felker, {G. Michael} and Januzzi, {James L.} and Christopher O'Connor and Javed Butler and Ambarish Pandey",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = nov,

doi = "10.1016/j.jchf.2023.03.007",

language = "English (US)",

volume = "11",

pages = "1507--1517",

journal = "JACC: Heart Failure",

issn = "2213-1779",

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number = "11",

}

TY - JOUR

T1 - Polypharmacy and Optimization of Guideline-Directed Medical Therapy in Heart Failure

T2 - The GUIDE-IT Trial

AU - Khan, Muhammad Shahzeb

AU - Singh, Sumitabh

AU - Segar, Matthew W.

AU - Usman, Muhammad Shariq

AU - Keshvani, Neil

AU - Ambrosy, Andrew P.

AU - Fiuzat, Mona

AU - Van Spall, Harriette G.C.

AU - Fonarow, Gregg C.

AU - Zannad, Faiez

AU - Felker, G. Michael

AU - Januzzi, James L.

AU - O'Connor, Christopher

AU - Butler, Javed

AU - Pandey, Ambarish

PY - 2023/11

Y1 - 2023/11

N2 - Background: Polypharmacy is common among patients with heart failure with reduced ejection fraction (HFrEF). However, its impact on the use of optimal guideline-directed medical therapy (GDMT) is not well established. Objectives: This study sought to evaluate the association between polypharmacy and odds of receiving optimal GDMT over time among patients with HFrEF. Methods: The authors conducted a post hoc analysis of the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial. Polypharmacy was defined as receiving ≥5 medications (excluding HFrEF GDMT) at baseline. The outcome of interest was optimal triple therapy GDMT (concurrent administration of a renin-angiotensin-aldosterone blocker and beta-blocker at 50% of the target dose and a mineralocorticoid receptor antagonist at any dose) achieved over the 12-month follow-up. Multivariable adjusted mixed-effect logistic regression models with multiplicative interaction terms (time × polypharmacy) were constructed to evaluate how polypharmacy at baseline modified the odds of achieving optimal GDMT on follow-up. Results: The study included 891 participants with HFrEF. The median number of non-GDMT medications at baseline was 4 (IQR: 3-6), with 414 (46.5%) prescribed ≥5 and identified as being on polypharmacy. The proportion of participants who achieved optimal GDMT at the end of the 12-month follow-up was lower with vs without polypharmacy at baseline (15% vs 19%, respectively). In adjusted mixed models, the odds of achieving optimal GDMT over time were modified by baseline polypharmacy status (P for interaction < 0.001). Patients without polypharmacy at baseline had increased odds of achieving GDMT (OR: 1.16 [95% CI: 1.12-1.21] per 1-month increase; P < 0.001) but not patients with polypharmacy (OR: 1.01 [95% CI: 0.96-1.06)] per 1-month increase). Conclusions: Patients with HFrEF who are on non-GDMT polypharmacy have lower odds of achieving optimal GDMT on follow-up.

AB - Background: Polypharmacy is common among patients with heart failure with reduced ejection fraction (HFrEF). However, its impact on the use of optimal guideline-directed medical therapy (GDMT) is not well established. Objectives: This study sought to evaluate the association between polypharmacy and odds of receiving optimal GDMT over time among patients with HFrEF. Methods: The authors conducted a post hoc analysis of the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial. Polypharmacy was defined as receiving ≥5 medications (excluding HFrEF GDMT) at baseline. The outcome of interest was optimal triple therapy GDMT (concurrent administration of a renin-angiotensin-aldosterone blocker and beta-blocker at 50% of the target dose and a mineralocorticoid receptor antagonist at any dose) achieved over the 12-month follow-up. Multivariable adjusted mixed-effect logistic regression models with multiplicative interaction terms (time × polypharmacy) were constructed to evaluate how polypharmacy at baseline modified the odds of achieving optimal GDMT on follow-up. Results: The study included 891 participants with HFrEF. The median number of non-GDMT medications at baseline was 4 (IQR: 3-6), with 414 (46.5%) prescribed ≥5 and identified as being on polypharmacy. The proportion of participants who achieved optimal GDMT at the end of the 12-month follow-up was lower with vs without polypharmacy at baseline (15% vs 19%, respectively). In adjusted mixed models, the odds of achieving optimal GDMT over time were modified by baseline polypharmacy status (P for interaction < 0.001). Patients without polypharmacy at baseline had increased odds of achieving GDMT (OR: 1.16 [95% CI: 1.12-1.21] per 1-month increase; P < 0.001) but not patients with polypharmacy (OR: 1.01 [95% CI: 0.96-1.06)] per 1-month increase). Conclusions: Patients with HFrEF who are on non-GDMT polypharmacy have lower odds of achieving optimal GDMT on follow-up.

KW - GDMT

KW - heart failure with reduced ejection fraction (HFrEF)

KW - polypharmacy

KW - triple therapy

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Polypharmacy and Optimization of Guideline-Directed Medical Therapy in Heart Failure: The GUIDE-IT Trial

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