COMMENTARY

Polypharmacy in Heart Failure: Progress But Also

Problem
To be clear, we are not suggesting that guideline-
SEE RELATED COMMENTARY, p. 1068
directed medical therapy (GDMT) be abandoned in the set-
ting of polypharmacy. Robust data support the many bene-
fits of GDMT,5 and we advocate for the broad uptake of
We read the commentary “Polypharmacy in Heart Fail-
GDMT to improve outcomes. However, to maximize the
ure with Reduced Ejection Fraction: Progress—not Prob-
potential benefits and mitigate the risks of each individual
lem” by Rao et al1 with great interest, but we respectfully
agent as well as the attendant risks of polypharmacy, risk
disagree with the authors on several points. We believe that
factors for harm should be routinely assessed and incorpo-
the increasing attention on polypharmacy and its implica-
rated into decision-making and prescribing practice. Risks
tions among patients with heart failure2 is a positive devel-
quantified by clinical trial data may be underestimated
opment. To provide holistic goal-concordant patient-
because randomized controlled trials have traditionally
centered care, it is essential to integrate concepts that have
excluded populations most vulnerable to adverse drug
traditionally been recognized in geriatric medicine into the
events such as older adults and those with multimorbid-
care of patients with heart failure, the majority of whom are
ity.6,7 Additionally, relying on clinical trial data alone to
older adults.3 This is in fact the premise of an entire field
quantify potential benefit may be problematic because such
known as geriatric cardiology.4
studies can only provide average treatment effects.8 This is
Within the context of polypharmacy and the increasing
relevant because “average” inherently means that some
number of pharmacologic agents recommended to treat
patients will derive more benefit and some will derive less
heart failure with reduced ejection fraction (HFrEF), the
benefit. Part of practicing clinical medicine is identifying
authors opine that the perceived risk of adverse events is
which patients will derive benefit and which will not.
not universally relevant. Wait—what happened to primum
Decisions such as these should not depend purely on
non nocere? We maintain that the risk for adverse events
anecdote or clinical intuition. Rather, decisions should
should always be considered when prescribing medication.
be made via careful consideration of the unique features
Further, this becomes increasingly important as the risk fac-
of each individual patient driving risk for harm and
tors for adverse drug events accumulate as it does in many
potential for benefit. Given this imperative, we advocate
patients with heart failure. Advancing age, multimorbidity,
for formally assessing multiple different domains that
cognitive impairment, and polypharmacy have all been
include polypharmacy as well as malnutrition, cognitive
shown to increase risk for adverse drug events. Given their
impairment, frailty, disability, and history of falls. Relat-
prevalence among patients with heart failure,3 we advocate
edly, we strongly endorse broad uptake of the domain
for explicit consideration of these risks in every patient
management approach to caring for older adults with
with heart failure.
heart failure because it offers a specific framework to
Funding: None.
guide overall care of these complex patients and sets a
Conflicts of Interest: PG is supported by American Heart Association foundation for patient-centered decision-making as it
grant 20CDA35310455, National Institute on Aging grant K76AG064428, relates to medication prescribing.9,10
and Loan Repayment Program award L30AG060521; receives personal We suggest caution in oversimplifying risk-benefit
fees for medicolegal consulting related to heart failure; and has assessments. The authors’ contention that “avoiding opti-
received honoraria from Akcea Inc and Bionest Inc. SM is supported by
the National Institute on Aging grant K76AG064428-01A1.
mal medical therapy also has its consequences, and they are
Authorship: All authors had access to the data and a role in writing likely worse than the issues with polypharmacy itself” may
this manuscript. be true for some, but not for all. The figure included in the
Additional corrections: Request for reprints should be addressed to authors’ commentary outlines some of the risks of poly-
Parag Goyal, MD, MSc, Assistant Professor of Medicine, Department of pharmacy but mischaracterizes quality of life and hospital-
General Internal Medicine, Division of Cardiology, Weill Cornell Medi-
cine, 420 E 70th Street, New York, NY 10021.
izations. Quality of life is only shown as a “benefit” of
E-mail address: pag9051@med.cornell.edu polypharmacy; however, this overlooks the concept of

0002-9343/© 2021 Elsevier Inc. All rights reserved.

https://doi.org/10.1016/j.amjmed.2021.05.007
1072
BENEFITS OF GDMT
PATIENT GOALS/
PRIORITIES
MEDICAL
PHYSICAL
FUNCTION
DOMAIN MANAGEMENT APPROACH
Figure Benefits of guideline-directed medical therapy (GDMT) and potential risks of polypharmacy.
treatment burden. Treatment burden is defined as workload
imposed by health care on patients and can reduce quality
of life.11 Similarly, a reduction in hospitalizations is only
shown as a “benefit” of polypharmacy; however, this
overlooks data demonstrating that polypharmacy is asso-
ciated with a significant increase in adverse drug event-
related hospitalizations.12 We propose a revised version
of the figure that we believe better reflects these reali-
ties. The revised figure additionally highlights the
importance of eliciting patient preferences and health
priorities when prescribing medication, which is repre-
sented by the fulcrum of the scale that links to the
domain management approach. We believe this figure
reflects a more nuanced and patient-centered approach
to balancing the potential benefits of GDMT and risks
of polypharmacy.
The American Journal of Medicine, Vol 134, No 9, September 2021
RISKS OF POLYPHARMACY
MIND &
EMOTION
SOCIAL
ENVIRONMENT
We fully agree with the authors that “now is the
time to balance implementation of maximally pres-
cribing existing guideline-directed medical therapies that
work with minimizing patient intolerances or adverse
symptoms.” However, this does not mean that more is nec-
essarily better for all patients. There is an inherent tension
between GDMT and polypharmacy, and we encourage
clinicians to perform individualized risk-benefit assess-
ments (guided by the domain management approach), elicit
patient preferences and priorities, and engage in a shared
decision-making process when considering medications,
even those that appear in clinical practice guidelines.
Although we acknowledge that this may be a time-consum-
ing process,13 we believe it is necessary to optimize medi-
cation-prescribing practice for older adults with heart
failure with reduced ejection fraction. This supports the
Goyal et al Polypharmacy Progress and Problems in Heart Failure
urgency to modify current reimbursement strategies in the
United States health care system to incentivize clinicians to
engage in such care, as well as the need to develop strate-
gies that can assist patients and clinicians with this increas-
ingly prevalent and complex conundrum.
Parag Goyal, MD, MSca
Sabrina Mangal, PhD, RNb
Ashok Krishnaswami, MD MASc
Michael W. Rich, MDd
a patients from ongoing clinical trials regarding heart failure. Arch
Department of General Internal
Medicine, Division of Cardiology,
Weill Cornell Medicine, New York,
NY
b
Department of Population Health
Sciences, Weill Cornell Medicine,
New York, NY
c 9. Gorodeski EZ, Goyal P, Hummel SL, et al. Domain management
Division of Cardiology, Kaiser
Permanente San Jose Medical
Center, San Jose, Calif
d a multidomain approach to caring for older adults with heart fail-
Cardiovascular Division,
Washington University School of
Medicine, St. Louis, Mo
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