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



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Annals of Pharmacotherapy
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DOI: 10.1177/1060028019849664
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
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
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)
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.
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.
The authors received no financial support for the research, author-
ship, and/or publication of this article.
Mohamed Mohamoud
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3. Tippett EC, Chen BK. Association of Attorney Advertising
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4. American Medical Association. Attorney ads on drug
side effects H-105.985.
HOD-105.985.xml. Accessed July 22, 2018.
5. Tippett E. Medical advice from lawyers: a content analy-
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... 40 Adherence can also be influenced by factors that seem to be entirely outside of health care; a recent study suggested that DOAC adherence could potentially be affected by personal injury attorney advertisements. 41 Furthermore, the clinical outcome of using OACs as preventive therapy, the absence of symptomatic thromboembolism, is silent. Patients cannot self-monitor or observe an immediate or direct effect on OAC's target outcome when taking these drugs. ...
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Background: Adherence to chronic medications remains poor in practice. There is limited evidence on how hospitalization affects post-discharge adherence to oral anticoagulants (OACs) in individuals with atrial fibrillation (AF). The aim of this study is to examine the impact of hospitalization and medication switching on post-discharge adherence to OACs in the AF population. Methods: A quasi-experimental pre-post observational study was conducted using United States commercial insurance healthcare claims from the 2009-2016 OptumTM . AF adults taking OACs who had a random hospitalization occurring after the first observed OAC prescription fill and no other admission in the preceding and following six months were identified. OAC adherence was estimated by the proportion of days covered (PDC) within six and twelve months before and after hospitalization. Difference-in-difference (DID) analysis was employed to compare pre- and post-hospitalization PDCs, stratified by reasons for hospitalization (i.e., bleeding versus nonbleeding-related reasons) and adjusting for imbalanced baseline characteristics between groups. Change in adherence when the OAC was switched at discharge was also examined. Results: The 22,429 individuals who met study criteria were predominantly male (52.4%), white (77.2%), and older age (median 74 years). A clinically significant hemorrhage was the reason for 1,029 (4.5%) of qualifying hospitalizations. After covariate adjustment, there was a reduction in PDC after discharge, regardless of admission diagnosis (p<0.0001). Six-month DID analyses revealed that adherence was incrementally reduced by 3.2% (p=0.0003) in the bleeding group compared to nonbleeding group, whereas switching from warfarin to a direct oral anticoagulant after hospitalization was associated with a smaller reduction by 3.4% in adherence (p=0.0342) compared to other switchers, regardless of the reason for hospitalization. Twelve-month DID analyses revealed similar results. Conclusions: Hospitalization is temporally associated with a reduction in adherence to OACs, regardless of reason for hospitalization. More effective strategies are needed to improve OAC adherence, particularly during transition of care.
Background Patients are often exposed to contradictory information about pharmaceutical products from various types of advertising. For example, direct-to-consumer advertising (DTCA) tend to emphasize a drug's benefits, while drug injury advertising emphasizes the worst side effects. Regarding DTCA as a drug information source, many researchers in pharmacy field focus on investigating the misinformation in DTCA and corrective advertising. However, no prior research has examined the effects of such contradictory advertising messages on patients' prescription medicine-related beliefs and medication adherence. This is a significant gap in the research literature on pharmaceutical advertising effects and medication adherence. Objective This is aimed to examine how exposure to DTCA and drug injury advertising would influence patients’ chronic accessibility of drug-related beliefs and their medication adherence behavior. Methods An online survey was conducted with a sample of 213 patients taking prescription blood thinners. Results The findings from this study did not support the predicted relationship between exposure to DTCA and consumers' drug-related belief accessibility or their medication adherence. However, this study found a significant interaction effect of exposure to DTCA and exposure to drug injury ads on patients’ medication adherence. The analysis results demonstrate that, for those who were exposed to drug injury ads, a significant negative relationship emerged between DTCA exposure and medication adherence. Conclusion This study provides important empirical evidence of a negative interaction effect of exposure to DTCA and drug injury ads on patients' medication adherence, which demonstrates that the influence of DTCA and drug injury ad exposures on patients' medication adherence is not independent, separate process but an interactive process. A communication campaign with corrective advertising could alleviate the negative interaction effect of exposure to contradictory information from different types of pharmaceutical ads on patients’ medication adherence.
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This study examined the medical information contained in a sample of television ads soliciting consumers for lawsuits against drug and medical device manufactures. Almost all such ads involved drugs or devices that have not been recalled and remain on the market. These ads raise important public health questions because they may influence the prospective medical decisions of viewers. The ads contained extensive descriptions of serious adverse events associated with the drugs or devices but almost uniformly failed to disclose information relating to the likelihood of such events. They also failed to effectively advise viewers to consult a doctor. Results also identified a subset of ads that mimicked public service announcements, claiming to be a “medical alert” “consumer alert” or “FDA warning” at the start of the ad. Most such ads did not disclose the attorney source of the advertising until the final few seconds.
Introduction Attorneys sponsor television advertisements that include repeated warnings about adverse drug events to solicit consumers for lawsuits against drug manufacturers. The relationship between such advertising, safety actions by the US Food and Drug Administration (FDA), and healthcare use is unknown. Objectives To investigate the relationship between attorney advertising, FDA actions, and prescription drug claims. Methods The study examined total users per month and prescription rates for seven drugs with substantial attorney advertising volume and FDA or other safety interventions during 2009. Segmented regression analysis was used to detect pre-intervention trends, post-intervention level changes, and changes in post-intervention trends relative to the pre-intervention trends in the use of these seven drugs, using advertising volume, media hits, and the number of Medicare enrollees as covariates. Data for these variables were obtained from the Center for Medicare and Medicaid Services, Kantar Media, and LexisNexis. Results Several types of safety actions were associated with reductions in drug users and/or prescription rates, particularly for fentanyl, varenicline, and paroxetine. In most cases, attorney advertising volume rose in conjunction with major safety actions. Attorney advertising volume was positively correlated with prescription rates in five of seven drugs, likely because advertising volume began rising before safety actions, when prescription rates were still increasing. On the other hand, attorney advertising had mixed associations with the number of users per month. Conclusion Regulatory and safety actions likely reduced the number of users and/or prescription rates for some drugs. Attorneys may have strategically chosen to begin advertising adverse drug events prior to major safety actions, but we found little evidence that attorney advertising reduced drug use. Further research is needed to better understand how consumers and physicians respond to attorney advertising.
Objective To assess the penetration of media-based information on transvaginal mesh (TVM) in our patient population and to determine whether exposure affects patient opinion. Since the 2011 Federal Drug Administration communication on TVM, many advertisements from legal practices have been directed toward patients. Materials and Methods An 18-item survey was administered to female patients at 2 sites from August 2012 to April 2013. Patients presenting with new diagnoses of pelvic organ prolapse or stress urinary incontinence or patients who reported prior mesh surgery were excluded. Results Ninety-nine questionnaires were completed. Sixty-six of the patients (67%) were aware of TVM; and of these, 38 (58%) cited advertisements as the initial source of information. Only 12% were aware of the Food and Drug Administration's communication. Regarding opinion of TVM, 9% chose “it is a safe product,” 9% “safety depends on factors related to patient,” 4.5% “not a safe product,” 1.5% “safety depends on the doctor,” 68% “I don't know,” and 4.5% marked 2 selections. Only 12% indicated knowing the difference in the use of TVM for pelvic organ prolapse vs stress urinary incontinence. When asked what influenced their opinion of TVM the most; responses were as follows: advertisement (33.3%), medical professional (22.7%), friends or family who underwent TVM procedure (12.1%), media article (6.1%), and “not sure” (25.8%). Conclusion Advertisements of TVM lawsuits had a high penetration into our patient population but did not produce an overtly negative response in our sample. Clinicians should be aware of the impact of these advertisements on patient opinion and counsel patients accordingly with unbiased and scientifically accurate information.
The purpose of this study was to understand the possible risk of discontinuation in the context of clinical care. Rivaroxaban is noninferior to warfarin for preventing stroke in atrial fibrillation patients. Concerns exist regarding possible increased risk of stroke and non-central nervous system (CNS) thromboembolic events early after discontinuation of rivaroxaban. We undertook a post-hoc analysis of data from the ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation, n = 14,624) for stroke or non-CNS embolism within 30 days after temporary interruptions of 3 days or more, early permanent study drug discontinuation, and end-of-study transition to open-label therapy. Stroke and non-CNS embolism occurred at similar rates after temporary interruptions (rivaroxaban: n = 9, warfarin: n = 8, 6.20 vs. 5.05/100 patient-years, hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 0.49 to 3.31, p = 0.62) and after early permanent discontinuation (rivaroxaban: n = 42, warfarin: n = 36, 25.60 vs. 23.28/100 patient-years, HR: 1.10, 95% CI: 0.71 to 1.72, p = 0.66). Patients transitioning to open-label therapy at the end of the study had more strokes with rivaroxaban (n = 22) versus warfarin (n = 6, 6.42 vs. 1.73/100 patient-years, HR: 3.72, 95% CI: 1.51 to 9.16, p = 0.0044) and took longer to reach a therapeutic international normalized ratio with rivaroxaban versus warfarin. All thrombotic events within 30 days of any study drug cessation (including stroke, non-CNS embolism, myocardial infarction, and vascular death) were similar between groups (HR: 1.02, 95% CI: 0.83 to 1.26, p = 0.85). In atrial fibrillation patients who temporarily or permanently discontinued anticoagulation, the risk of stroke or non-CNS embolism was similar with rivaroxaban or warfarin. An increased risk of stroke and non-CNS embolism was observed in rivaroxaban-treated patients compared with warfarin-treated patients after the end of the study, underscoring the importance of therapeutic anticoagulation coverage during such a transition.