Elsevier

JACC: Heart Failure

Volume 11, Issue 11, November 2023, Pages 1507-1517
JACC: Heart Failure

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

https://doi.org/10.1016/j.jchf.2023.03.007Get rights and content

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.

Section snippets

Study design and participants

Data for the current analysis were obtained from the National Institute of Health Biologic Specimen and Data Repository Coordinating Center. The design and primary results of the GUIDE-IT trial have been published previously.14,15 In brief, the GUIDE-IT trial, which was conducted between 2013 and 2016, enrolled 894 patients with HFrEF (left ventricular ejection fraction of <40%) and randomized them in a 1:1 fashion to either usual care or NT-proBNP–guided therapy. Patients in the usual care arm

Results

Among the 894 participants enrolled in the GUIDE-IT trial, 891 had data on baseline medication count and were included in the current analysis. At baseline, 604 (67.8%) and 30 (3.4%) participants were prescribed >5 and >10 total medications, respectively, and 79 (8.9%) were on optimal GDMT. Among non-GDMT medications, the median was 4 (IQR: 3-6), with 414 (46.5%) prescribed ≥5 non-GDMT medications at baseline and identified as being on polypharmacy. The most used non-GDMT medications were

Discussion

This post hoc analysis of the GUIDE-IT trial identified several key findings. First, non-GDMT polypharmacy is highly prevalent among patients with HFrEF, with >46% on 5 or more non-GDMT medications. Second, although the odds of achieving optimal GDMT increased over time in the overall cohort, they were modified by the baseline burden of polypharmacy such that those with a higher number of non-GDMT medications had a lower probability of reaching optimal GDMT. Finally, increasing count of

Conclusions

The findings of this study suggest that patients with HFrEF who are on non-GDMT polypharmacy are more likely to experience underuse of GDMT despite being at higher risk for adverse clinical outcomes. Future studies are needed to determine whether the implementation of multidisciplinary interventions to lower the polypharmacy burden may improve GDMT uptake among patients with HFrEF.

COMPETENCY IN MEDICAL KNOWLEDGE: Patients with HFrEF who are on polypharmacy (ie, use of ≥5 non-HF medications) are

Funding Support and Author Disclosures

Dr Pandey has received research support from the National Institute on Aging GEMSSTAR grant (1R03AG067960-01) and the National Institute on Minority Health and Disparities (R01MD017529); grant funding from Applied Therapeutics and Gilead Sciences; honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, and Roche Diagnostics; nonfinancial support from Pfizer and Merck; and is a consultant for Palomarin Inc with stock compensation. Dr

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