Polypharmacy lowers odds for initiating recommended heart failure medications
Key takeaways:
- Patients prescribed five or more drugs are more likely to experience underuse of guideline-directed medical therapy for HF.
- Data highlight the unique challenges to optimal HFrEF management among older adults.
Patients prescribed a higher number of overall medications had a lower probability of initiating or achieving optimal guideline-directed medical therapy for HF, despite higher risk for long-term outcomes, data show.
In a post hoc analysis of the GUIDE-IT trial, which evaluated the efficacy of a biomarker-guided approach for management of HF with reduced ejection fraction, researchers observed that non-guideline-directed medical therapy (GDMT) polypharmacy is highly prevalent among patients with HFrEF, with more than 46% prescribed five or more non-GDMT medications.
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“Several factors among older patients with HFrEF may adversely affect optimal GDMT use and long-term clinical outcomes,” Ambarish Pandey, MD, MSCS, assistant professor of internal medicine at University of Texas Southwestern Medical Center, and colleagues wrote in JACC: Heart Failure. “These include the increasing prevalence of comorbidities such as chronic kidney disease, atrial fibrillation, coexisting depression and cognitive impairment and a high burden of frailty. Polypharmacy, most commonly defined as the concomitant use of five or more medications, is also common and associated with an increased risk of adverse outcomes among community-dwelling individuals with HFrEF. However, the association between polypharmacy and GDMT uptake and downstream clinical outcomes in patients with HFrEF has not been evaluated in these studies due to their observational nature, lack of longitudinal data on GDMT uptitration, and lack of an intervention to promote GDMT uptitration in these cohort studies.”
Polypharmacy burden high
Pandey and colleagues analyzed data from 891 patients with HFrEF (EF < 40%) who participated in GUIDE-IT, conducted between 2013 and 2016. For the original study, researchers randomly assigned patients to usual care or to therapy guided by N-terminal pro-B-type natriuretic peptide, with medications titrated with the goal of achieving and maintaining NT-proBNP levels of less than 1,000 pg/mL. The researchers defined polypharmacy as receiving five or more medications that were not related to GDMT for HFrEF at baseline. The primary outcome was optimal triple therapy GDMT, defined as 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 during the 12-month follow-up.
Researchers used logistic regression models to evaluate how polypharmacy at baseline modified the odds of achieving optimal GDMT on follow-up.
Within the cohort, the median number of non-GDMT medications at baseline was four, with 46.5% of participants prescribed more than five drugs and identified as being on polypharmacy.
“Participants with polypharmacy were older and had a significantly higher burden of cardiac and noncardiac comorbidities, greater severity of HF and worse quality of life,” the researchers wrote.
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 < .001) Participants without polypharmacy at baseline were 16% more likely to achieve GDMT during follow-up, with an OR of 1.16 per 1-month increase (95% CI, 1.12-1.21; P < .001).
GDMT interventions needed
Researchers noted that the underuse of optimal GDMT in patients with polypharmacy may be related to several factors.
“First, patients with polypharmacy often are older, have a higher burden of comorbidities and have a higher frailty burden, which may contribute to increased inertia to GDMT uptitration among providers,” the researchers wrote. “Furthermore, in some cases, non-GDMT polypharmacy may contribute to intolerance to specific GDMT because of a higher risk of adverse effects, drug-drug interactions, nonadherence due to high pill burden and high cumulative out-of-pocket costs. Moreover, the lack of shared values for GDMT initiation and uptitration between patients and providers may undermine the importance of optimal GDMT from a patient’s perspective and add to their underuse.”
The researchers wrote that the implementation of multidisciplinary interventions to lower the polypharmacy burden may improve GDMT uptake among patients with HFrEF, but more research on ideal interventions is needed.
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