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Polypharmacy and Optimization of Guideline-Directed HF Therapy
Quick Takes
- Polypharmacy in older adults is common and is associated with a lower probability of achieving optimal guideline-directed therapy for heart failure.
- Heart failure patients with polypharmacy are more likely to experience long-term adverse clinical outcomes.
Study Questions:
Is polypharmacy associated with lower odds of initiation and uptitration of guideline-directed medical therapy (GDMT) among older adults with heart failure with reduced ejection fraction (HFrEF)?
Methods:
The GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial randomized patients with a left ventricular EF <40% (HFrEF) to receive either usual care with GDMT or N-terminal pro–B-type natriuretic peptide (NT-proBNP)–guided therapy. The current study, a post hoc analysis of the GUIDE-IT trial, compared the subpopulation of patients with polypharmacy (receiving ≥5 medications, excluding HFrEF GDMT and diuretics) to those without polypharmacy at baseline. The primary outcome was the proportion of patients treated with optimal GDMT defined as concurrent administration of a renin-angiotensin-aldosterone blocker and beta-blocker ≥50% of the target dose plus a mineralocorticoid receptor antagonist (MRA) at any dose at the 12-month follow-up. Multivariate adjusted mixed-effect logistic regression models were used to evaluate how polypharmacy at baseline impacted the odds of achieving optimal GDMT. Clinical outcomes included the primary endpoint from GUIDE-IT (composite of time to first hospitalization for HF or cardiovascular mortality), all-cause mortality, and HF hospitalization. Changes in health-related quality of life using the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score were also assessed.
Results:
A total of 891 patients with HFrEF were included. The median number of non-GDMT medications at baseline was 4 (interquartile range, 3-6). Polypharmacy (≥5 medications) was present in 414 patients (46.5%). Patients with polypharmacy were older, had a greater severity of HF (higher mean New York Heart Association class and NT-proBNP levels, shorter 6-minute walk distance), and more cardiac and noncardiac comorbidities compared to patients without polypharmacy.
Patients with polypharmacy were less likely to achieve optimal GDMT than those without polypharmacy at baseline (15% vs. 19%). Of the individual GDMT components, optimal use of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker and MRA were less common in patients with polypharmacy, while optimal use of beta-blockers was similar between groups. Patients without polypharmacy at baseline had increased odds of achieving optimal GDMT (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.12-1.21) per 1-month follow-up, whereas patients with polypharmacy did not (OR, 1.01; 95% CI, 0.96-1.06).
At 12-month follow-up, the odds of achieving optimal GDMT were 19% lower among patients with versus without polypharmacy at baseline. Results were similar when adjusted for differences in comorbidity burden. Polypharmacy was associated with a higher incidence of the primary composite endpoint (HF hospitalization or cardiovascular mortality) in an unadjusted analysis, but not when adjusted for comorbidity burden (hazard ratio, 1.20; 95% CI, 0.94-1.53). A similar pattern of results was seen with other clinical outcomes including all-cause mortality and HF hospitalization. Patients with polypharmacy had lower quality of life than patients without polypharmacy as assessed by KCCQ clinical summary scores (polypharmacy yes vs. no, -4.67; 95% CI, -7.05 to -2.29).
Conclusions:
The findings of this study identify a high prevalence of non-GDMT polypharmacy among patients with HFrEF. Patients with polypharmacy were less likely to achieve optimal GDMT despite a higher risk of adverse clinical outcomes.
Perspective:
The findings of this study add to other observational data demonstrating a significant association between polypharmacy and adverse clinical outcomes in patients with HFrEF. This association has been attributed to the higher burden of comorbidities in patients who take more medications. This is important since these patients with more severe disease are likely to have greater benefit from optimal GDMT. Underutilization of GDMT in patients with polypharmacy may be due to several factors including lack of medication uptitration due to age, comorbidities, and/or frailty; risk of adverse effects or drug interactions; nonadherence due to pill burden; and high out-of-pocket drug costs. Although patients without polypharmacy were more likely to achieve optimal GDMT than those with polypharmacy, the overall rates of optimal GDMT were low regardless of baseline polypharmacy, highlighting the challenges to HFrEF management.
Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Adrenergic beta-Antagonists, Aldosterone, Angiotensin-Converting Enzyme Inhibitors, Biomarkers, Comorbidity, Diuretics, Geriatrics, Heart Failure, Mineralocorticoid Receptor Antagonists, Natriuretic Peptide, Brain, Patient Care Team, Polypharmacy, Quality of Life, Renin-Angiotensin System, Secondary Prevention, Stroke Volume
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