Discontinuation of Direct Oral Anticoagulants in Response to Attorney Advertisements: Data From the FDA Adverse Event Reporting System

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https://doi.org/10.1177/1060028019849664
Annals of Pharmacotherapy
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Letter to the Editor
The impact of attorney advertisements on patients’ deci-
sions to discontinue a direct oral anticoagulant (DOAC)
prematurely is not well examined, although some studies
have documented misinformation in attorney advertise-
ments associated with medical products.1-3 In 2016, the
American Medical Association recommended that attorney
advertisements include clear warnings that patients should
not discontinue medications without physician consulta-
tion, reflecting a consensus that attorney advertisements
may deter consumers from taking their medications.4
We searched the US Food and Drug Administration
(FDA) Adverse Event Reporting System (FAERS) to iden-
tify US reports of patients who discontinued or reduced the
dose of their DOACs (ie, dabigatran, rivaroxaban, apixa-
ban, and edoxaban) after viewing an attorney advertise-
ment, received by FDA from approval of each DOAC
through November 15, 2017. Using SAS version 9.4 (SAS
Institute Inc, Cary, NC), we conducted a narrative search of
all DOAC reports for terms that could indicate DOAC use
modification in reference to a television advertisement. We
included reports where a DOAC was discontinued or dose
reduced after viewing an attorney advertisement. We
excluded reports unrelated to the subject of interest, dupli-
cates, or reports with insufficient information.
We identified 66 reports that described patients who
viewed an advertisement and then discontinued (n = 65) or
reduced (n = 1) the dose of a DOAC, including 7 deaths
(Table 1). In most reports (64/66, 97%), DOAC discontinua-
tion occurred without physician consultation. We classified
the advertisements into 3 categories: “attorney” advertise-
ments (n = 25) clearly describe a law firm advertisement;
advertisements described as “1-800-BAD-DRUG” adver-
tisements (n = 13) appear to be announcements advising
consumers to contact a law firm5; and “unspecified” adver-
tisements were those without enough information to classify
the advertisement but that mentioned nonspecific terms such
as negative television commercials (n = 28). Among the 25
reports referencing an “attorney” advertisement, most patients
(18/25, 72%) experienced a stroke (n = 13), thromboembo-
lism (n = 4), or a transient ischemic attack (TIA) (n = 1) fol-
lowing DOAC discontinuation; 3 patients died. Most patients
who viewed “1-800-BAD-DRUG” advertisements (11/13,
85%) experienced a stroke (n = 8) or a thromboembolism (n
849664AOPXXX10.1177/1060028019849664Annals of PharmacotherapyMohamoud et al
letter2019
Discontinuation of Direct Oral
Anticoagulants in Response to
Attorney Advertisements: Data
From the FDA Adverse Event
Reporting System
Table 1. Characteristics of FAERS Reports of DOAC
Discontinuation or Dose Reduction After Viewing Attorney
Advertisements (n = 66 Reports).a
Selected Characteristics n (%)
Age (years), n = 35bRange 30-90
Median 70
Mean 68
Sex Male 27 (41)
Female 28 (42)
Unknown 11 (17)
Reason for use Atrial fibrillation 36 (55)
Thromboembolism 13 (20)
Unknown 17 (25)
DOAC Rivaroxaban 55 (83)
Dabigatran 8 (12)
Apixaban 3 (5)
Edoxaban 0
Reporter Health care professional 50 (76)
Consumer 16 (24)
Advertisement type Attorneyc25 (38)
1-800-BAD-DRUGd13 (20)
Unspecified 28 (42)
Advertisement medium Television ads 38 (58)
Direct mail ads 1 (2)
Unknown 27 (40)
Disposition of therapy after
viewing advertisement
Discontinued 65 (98)
Dose reduced 1 (2)
DOAC discontinuation or
dose reduction resulted
in a reported adverse
event
Yes 47 (71)
No 19 (29)
Subsequent reported
adverse event
Stroke 33 (50)
Thromboembolisme11 (17)
Transient ischemic attack 2 (3)
Not reportedf1 (2)
Unknown 19 (29)
Serious outcomesg,h Death 7 (11)
Life-threatening 1 (2)
Hospitalization 26 (39)
Other serious 24 (36)
Disability 1 (2)
Unknown 13 (20)
(continued)

2 Annals of Pharmacotherapy 00(0)
= 3); 2 patients died. Similarly, of the remaining 28 patients
who viewed “unspecified” advertisements, more than half
(17/28, 61%) experienced a stroke (n = 12), thromboembo-
lism (n = 4), or TIA (n = 1); 2 patients died.
Our findings provide evidence consistent with a previ-
ous study showing attorney advertising influenced
patients to discontinue rivaroxaban.2 We found that attor-
ney advertisements may influence patients to discontinue
or reduce the dose of their DOAC without medical advice,
which places this group at heightened risk of thromboem-
bolic events. Although it is expected that DOAC discon-
tinuation contributed to the thromboembolic outcomes, it
is unknown how many events would have occurred
despite drug continuation. However, in the ROCKET-AF
trial, an increased risk of stroke was observed among
rivaroxaban patients who temporarily or permanently dis-
continued anticoagulation.6 Limitations of our assess-
ment are consistent with those of spontaneously reported
data and include underreporting, selective reporting, and
the lack of event adjudication. The FDA uses its regula-
tory authority to ensure that prescription drug promotion
by manufacturers is truthful, balanced, and not mislead-
ing. Furthermore, the regulation of attorney advertise-
ments is typically through state attorney ethics rules.5
Given the severity of the outcomes reported to the FDA,
we believe that it is imperative for clinicians to counsel
DOAC users about the risks of therapy modification in
the absence of medical consultation.
Mohamed Mohamoud, PharmD, MPH
Saharat Patanavanich, PharmD
Page Crew, PharmD, MPH
Lynda McCulley, PharmD
Monica Munoz, PharmD, PhD
Cindy Kortepeter, PharmD
S. Christopher Jones, PharmD, MPH, MS
Abbreviations: DOAC, direct oral anticoagulant; FAERS, US Food and
Drug Administration Adverse Event Reporting System.
aAs of November 15, 2017.
bRefers to the number of cases in which the specific demographic data
were provided; balance of total had incomplete data.
cAttorney advertisements: clearly described a law firm advertisement.
d1-800-BAD-DRUG ads: Announcements referencing “bad drug” that
appear to be public service announcements describing side effects of a
product advising consumers to contact a third party or a law firm.
eThromboembolic events include pulmonary embolism, deep-vein
thrombosis, splenic infarct, and “blood clots.”
fReport of death, but adverse event was not specified.
gMore than 1 serious outcome is possible.
hPer 21 CFR 314.80, the regulatory definition of serious is any adverse
drug experience occurring at any dose that results in any of the
following outcomes: death, a life-threatening adverse drug experience,
inpatient hospitalization or prolongation of existing hospitalization, a
persistent or significant disability/incapacity, a congenital anomaly/birth
defect, and other serious important medical events.
Table 1. (continued) Daniel Woronow, MD, FACC
Gerald Dal Pan, MD, MHS
United States Food and Drug Administration, Silver
Spring, MD, USA
Authors’ Note
All authors had access to the data and played a role in writing the
article. The views presented in this article are those of the authors
and not necessarily those of the US Food and Drug Administration
or the US Government.
Acknowledgments
The authors thank Judith Zander and Michael Blum for their careful
reading and helpful suggestions in the preparation of this article.
Declaration of Conflicting Interests
The authors declared the following potential conflicts of interest
with respect to the research, authorship, and/or publication of this
article: The authors are all employees of the US Food and Drug
Administration and have no financial conflicts to report.
Funding
The authors received no financial support for the research, author-
ship, and/or publication of this article.
ORCID iD
Mohamed Mohamoud https://orcid.org/0000-0002-5997-4876
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