Editor's Note: Commentary based on Goyal P, Bryan J, Kneifati-Hayek J, et al. Association between functional impairment and medication burden in adults with heart failure. J Am Geriatr Soc 2019;67:284-91.

Rationale for Study/Background

Polypharmacy is most often defined as concurrent use of five or more medications,^1-3 and is often present in older adults with chronic heart failure (CHF).⁴ Furthermore, many older adults with CHF have concomitant limitations in functional abilities,⁵ and polypharmacy is generally associated with a decline in functional status and worse outcomes overall.³ Moreover, guideline concordant therapy in CHF often leads to polypharmacy.⁶ The authors of this paper sought to examine whether there was a difference in the number of medications prescribed to older adults with CHF with and without activity limitations.

Funding

Dr. Safford reports research support from Amgen. Dr. Goyal is supported by National Institute on Aging Grant R03AG056446.

Methods

This study used data from the National Health and Nutritional Examination Survey (NHANES), a nationally representative survey of the US population, excluding veterans and institutionalized individuals, that began in 1960.⁷ For this study, the 61,087 NHANES participants from 2003-2014 were eligible for inclusion.

Design: Cross-sectional cohort study

Inclusion Criteria: Adults age 50 and older with CHF. CHF was identified according to a previously validated self-report measure.

Exclusion Criteria: Individuals missing information on CHF, disability or number of medications.

Exposure: Polypharmacy was defined as five or more medications based on medication lists provided at NHANES in-home interviews.

Primary Outcome: Functional status, determined according to self-report of three select activities of daily living (ADLs) that were captured in the NHANES survey, specifically having difficulty with dressing, feeding oneself or transferring independently (e.g., getting in and out of bed).

Statistical Analysis: Sequential Poisson multivariable regression analyses were used to examine the association between limitation in ADLs and medication count. Models were built sequentially, adjusting first for "predisposing" factors: age, race and sex; "enabling" factors: insurance, education level attained, household income, marital status and living alone; comorbidities; "need" factors: smoking status, frailty (defined as albumin ≤3.3 g/dL) and self-reported memory impairment; and healthcare utilization factors. Multiple imputation was used for missing data. Sensitivity analyses were performed in those ≥65 years, and by only including medications used for at least 2 weeks. Interactions between ADL limitation and 3+ hospitalizations in the past year, declining self-reported health status, and cognitive impairment were assessed.

Results

In total, 947 participants, mean age 70 years, were included. Given the NHANES design, this represents about 4.6 million adults in the US living with CHF. The mean medication count was 7.2 (95% CI 6.8-7.5), with nearly three quarters of the cohort meeting the criteria for polypharmacy. The most common medications were beta-blockers (61%), diuretics (60%) and angiotensin receptor blockers (28%). Limitations in ADLs were reported by 11% of participants; among these, 64% had difficulty with dressing, 55% had difficulty with transferring and 22% with eating. Those with ADL limitations reported higher medication use compared to those without (mean 8.5 vs. 7.0). After adjustment, the difference in the number of medications taken by those with and without ADL limitation did not differ, even after stratifying by age. Compared to those with ADL limitations, the mean medication count for those without ADL limitation increased over time (p-trend 0.67 vs. 0.04). All a priori interactions were non-significant.

Limitations of Study

CHF was assessed according to self-report. Those with reduced ejection fraction (EF) versus preserved EF could not be assessed separately. ADL assessment typically includes six items: bathing, dressing, toileting, transferring, continence and feeding. That only three of these variables were captured likely leads to misclassification of individuals who have ADL limitations in categories not included. NHANES questionnaires also include information on ability to walk from room to room and rise from chair that have been included in other studes.⁸ Therefore, the conclusion that polypharmacy does not vary by ADL limitation amongst those with CHF may be premature. Individual goals of participants were not available to determine whether polypharmacy was in line with treatment goals. Long term outcomes of functional status, readmissions and mortality were not examined.

Conclusion

In a nationally representative sample of adults with CHF in the US, polypharmacy is common and does not differ according to ADL limitation. This may reflect a lack of clinicians incorporating functional status into prescribing decisions for older adults with CHF.

Geriatric Perspective for the Cardiovascular Clinician

This study reflects the success and conundrum of modern medicine – older adults with CHF are routinely prescribed multiple medications, following guidelines and evidenced based therapy, regardless of functional status. Since the 1980s, new molecular entities approved by the FDA have more than doubled, including many preventive medications regularly prescribed to patients with CHF (e.g., simvastatin 1991, metformin 1994 and lisinopril 2003).⁹ For many older adults, this begs the question as to whether clinicians are following guideline concordant or goal concordant treatment, particularly as most studies that lead to evidence based medicine have not included older adults with functional limitations.¹⁰ That nearly three quarters of the population studied met criteria for polypharmacy is striking, as in other cohorts of older adults the prevalence of polypharmacy is estimated to be 40-50%.^3,8,11 Similarly, in context of the medical advances of the last 30 years, another NHANES study demonstrated that the proportion of individuals over 65 taking no medications has declined from nearly 30% to 10%, with many prescribed medications considered preventive.8 At the same time, potentially inappropriate medication prescribing has decreased by almost half (from 28.2% to 15.1%),⁸ which may reflect increasing awareness of inappropriate medications for older adults since the first publication of the Beers list in 1991.¹² A challenge in caring for older adults is the prevailing assumption that with respect to intensity of care, "more is better" and "less is worse". In fact, prescribing cascades can occur when an additional medication is added to treat the side effect of another medication leading to adverse outcomes.¹³ However, a recent review of polypharmacy and prescribing cascades suggests that there are clinical scenarios in which this may be appropriate and in line with goals of care.¹⁴ As such, that no difference was found between groups may optimistically reflect appropriate polypharmacy following shared decision making. Furthermore, amongst those who had ADL limitations, the average medication count did not increase over time, which may reflect clinician sensitivity to declining functional abilities.

Greater polypharmacy may be a proxy for greater access to healthcare, and the absolute count of medications may incorrectly miss a carefully tailored regimen of lower doses of multiple medications that is in line with goals of care.¹⁵ Furthermore, while polypharmacy is associated with an increased risk of functional limitation, this may be attributable to reverse causation, particularly in CHF where worse function may be a signal of worsening CHF leading to additional medications. Future studies are needed to understand the benefits and harms of polypharmacy in older adults with CHF and functional limitations.

Take Home Message: Withholding medications from older individuals with CHF based on ADL limitations alone may be premature and should instead be based on a conversation with the patient that focuses on the individual's goals, desired outcomes, and the reality of what an additionally prescribed (or deprescribed) medication may offer.

References

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Keywords: Geriatrics, Heart Failure, Polypharmacy, Activities of Daily Living, Angiotensin Receptor Antagonists, National Institute on Aging (U.S.), Age Factors, Sex Factors, Comorbidity, Evidence-Based Medicine, Regression Analysis, Patient Care Planning

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