Transcript Evidence-based Guideline Update: NSAIDs, and other

Evidence-based guideline: Periprocedural
management of antithrombotic
medications in patients with ischemic
cerebrovascular disease
Report of the Guideline Development
Subcommittee of the American Academy of
Neurology
©2013 American Academy of Neurology
Guideline Endorsement
This guideline is endorsed by the American
Osteopathic Association, the European
Federation of Neurological Sciences, and
the European Neurological Society
©2013 American Academy of Neurology
Authors
 Melissa J. Armstrong, MD
 Gary Gronseth, MD, FAAN
 David C. Anderson, MD, FAAN, FAHA
 José Biller, MD, FACP, FAAN, FAHA
 Brett Cucchiara, MD
 Rima Dafer, MD, MPH, FAHA
 Larry B. Goldstein, MD, FAAN, FAHA
 Michael Schneck, MD, FAAN, FAHA, FACP
 Steven R. Messé, MD, FAAN
©2013 American Academy of Neurology
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©2013 American Academy of Neurology
Presentation Objectives
 To present the evidence regarding
periprocedural management of
antithrombotic drugs in patients with
ischemic cerebrovascular disease
 To present evidence-based
recommendations
©2013 American Academy of Neurology
Overview
 Background
 Gaps in care
 American Academy of Neurology (AAN) guideline
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
process
Analysis of evidence, conclusions,
recommendations
Recommendations for future research
©2013 American Academy of Neurology
Background
 Neurologists are frequently asked to recommend
whether practitioners should temporarily stop
anticoagulation (AC) and antiplatelet (AP) agents
in patients with prior strokes or transient
ischemic attacks (TIAs) undergoing invasive
procedures. The balance of risks of recurrent
vascular events with discontinuation of these
agents versus increased periprocedural bleeding
with continuation is often unclear, leading to
variability in care and possibly adverse outcomes.
©2013 American Academy of Neurology
Background, cont.
 This guideline reviews evidence regarding
periprocedural management of patients with a
history of ischemic cerebrovascular disease
receiving AC or AP agents. Four questions will be
addressed.
©2013 American Academy of Neurology
Clinical Questions
 What is the thromboembolic (TE) risk of
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temporarily discontinuing an antithrombotic
medication?
What are the perioperative bleeding risks of
continuing antithrombotic agents?
If oral AC is stopped, should bridging therapy be
used?
If an antithrombotic agent is stopped, what
should be the timing of discontinuation?
©2013 American Academy of Neurology
AAN Guideline Process
 Clinical Question
 Evidence
 Conclusions
 Recommendations
©2013 American Academy of Neurology
Literature Search/Review
 Rigorous, Comprehensive, Transparent
Search
Search
Review abstracts
Review full text
Relevant
©2013 American Academy of Neurology
Select articles
AAN Classification of Evidence
 All studies meeting inclusion/exclusion
criteria defined a priori rated Class I, II, III,
or IV
 Five different classification systems
• Therapeutic
Randomization, control, blinding
• Diagnostic
Comparison with reference standard
• Prognostic
• Screening
• Causation
©2013 American Academy of Neurology
AAN Level of Recommendations
 A = Established as effective, ineffective, or harmful (or
established as useful/predictive or not
useful/predictive) for the given condition in the
specified population
 B = Probably effective, ineffective, or harmful (or
probably useful/predictive or not useful/predictive)
for the given condition in the specified population
 C = Possibly effective, ineffective, or harmful (or
possibly useful/predictive or not useful/predictive) for
the given condition in the specified population
 U = Data inadequate or conflicting; given current
knowledge, treatment (test, predictor) is unproven
 Note that recommendations can be positive or negative
©2013 American Academy of Neurology
Translating Class to
Recommendations
 A = Requires at least two consistent Class I
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studies*
B = Requires at least one Class I study or two
consistent Class II studies
C = Requires at least one Class II study or two
consistent Class III studies
U = Assigned in cases of only one Class III study,
only Class IV studies, or evidence that is
conflicting and cannot be reconciled
* In exceptional cases, one convincing Class I study may suffice for an “A” recommendation if 1)
all criteria are met, 2) the magnitude of effect is large (relative rate improved outcome >5 and
the lower limit of the confidence interval [CI] is >2)
©2013 American Academy of Neurology
Applying the Process to the Issue
 We will now turn our attention to the
guideline.
©2013 American Academy of Neurology
Methods
 Literature searches of MEDLINE and EMBASE
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
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through August 2011 were performed in all
languages using relevant MeSH terms, text word
synonyms, and key words.
Authors reviewed each article for inclusion.
Risk of bias was determined using the
classification of evidence scheme for prognostic
articles.
Strength of recommendations was linked directly
to evidence levels.
Conflicts of interest were disclosed.
©2013 American Academy of Neurology
Literature Search/Review
 Rigorous, Comprehensive, Transparent
5,904
abstracts
Inclusion criteria:
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-
Studies of patients taking
oral antithrombotic agents
for primary or secondary
cardiovascular disease or
stroke prevention
Studies assessing risks of
continuation or
discontinuation and clearly
describing interventions
and outcome measures
Exclusion criteria:
-
133
articles
©2013 American Academy of Neurology
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Studies sampling < 20
subjects or lacking a
comparison group
Case reports, review
papers, articles on certain
procedures (see published
guideline for specifics)
AAN Classification of Evidence
for Prognostic Studies
 Class I: A cohort study of a broad spectrum of persons at risk for

developing the outcome (e.g., target disease, work status). The
outcome is defined by an acceptable reference standard for case
definition. The outcome is objective or measured by an
observer who is masked to the presence of the risk factor. Study
results allow calculation of measures of prognostic accuracy.
Class II: A case control study of a broad spectrum of persons
with the condition compared to a broad spectrum of controls or
a cohort study of a broad spectrum of persons at risk for the
outcome (e.g., target disease, work status) where the data was
collected retrospectively. The outcome is defined by an
acceptable reference standard for case definition. The outcome
is objective or measured by an observer who is masked to the
presence of the risk factor. Study results allow calculation of
measures of prognostic accuracy.
©2013 American Academy of Neurology
AAN Classification of Evidence
for Prognostic Studies, cont.
 Class III: A case control study or a cohort study where either the
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persons with the condition or the controls are of a narrow
spectrum where the data was collected retrospectively. The
outcome is defined by an acceptable reference standard for case
definition. The outcome is objective or measured by an
observer who did not determine the presence of the risk factor.
Study results allow calculation of measures of a prognostic
accuracy.
Class IV: Studies not meeting Class I, II, or III criteria, including
consensus, expert opinion, or a case report.
©2013 American Academy of Neurology
Conclusions and Recommendations
 Conclusions are available in the full guideline
document, published as an online data
supplement to the summary guideline
publication. Recommendations are available in
both the full guideline document and the
summary publication.
©2013 American Academy of Neurology
Clinical Question 1
 What is the TE risk of temporarily
discontinuing an antithrombotic
medication (APs and ACs)?
©2013 American Academy of Neurology
Conclusion:
TE Risk of Discontinuing AP Agents
 Aspirin discontinuation is probably associated with
increased stroke or TIA risk (one Class I study, two
Class II studies). Estimated stroke risk varies with the
duration of aspirin discontinuation: relative risk (RR)
was 1.97 for 2 weeks, odds ratio (OR) was 3.4 for 4
weeks, and RR was 1.40 for 5 months (one Class II
study each).
©2013 American Academy of Neurology
Conclusion:
TE Risk of Discontinuing
Anticoagulation
 No studies meeting inclusion criteria compared
TE risks in subjects continuing warfarin with those
discontinuing warfarin (with or without
periprocedural heparin bridging). Studies lacked
the statistical precision needed for conclusions to
be drawn (one Class I study, three Class II studies
with various methodologies). The TE event risk of
warfarin discontinuation is probably higher if AC
is stopped for ≥ 7 days (one Class I study).
©2013 American Academy of Neurology
Clinical Question 2a
 What are the perioperative bleeding
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risks of continuing AP agents?
Dental procedures
Ophthalmologic procedures
Dermatologic procedures
Electromyography (EMG)
Endoscopic procedures
Urologic procedures
Spinal or epidural anesthesia/pain procedures
Orthopedic procedures
Other procedures
©2013 American Academy of Neurology
Conclusions
Dental Procedures:
 It is highly probable that aspirin does not increase
minor bleeding in patients undergoing dental
surgery (two Class I studies, one Class II study).
However, the studies’ degree of statistical
precision fails to exclude an increased bleeding
risk of up to 8.3%.
 It is possible that dual AP therapy has no
increased bleeding risk over clopidogrel therapy
alone (one Class II study); no bleeding events
occurred in either group, but a bleeding risk of up
to 11.7% cannot be excluded.
©2013 American Academy of Neurology
Conclusions, cont.
Ophthalmologic Procedures:
 In three cataract studies (one Class I, one Class II, and
one Class III), aspirin did not increase clinically
important bleeding. However, the degree of statistical
precision in the less-biased Class I and Class II cataract
studies failed to exclude an increased bleeding risk of
up to 7.5%. One Class III cataract study found no
increase in clinically important bleeding with
clopidogrel use. In two Class II and two Class III
studies of ocular anesthesia, aspirin did not increase
clinically important bleeding.
 In two studies (one Class II, one Class III) of
procedures for glaucoma, aspirin use did not increase
clinically important bleeding.
 A single Class II study of vitreoretinal surgery found
no increase in clinically important bleeding in patients
continuing aspirin or clopidogrel.
©2013 American Academy of Neurology
Conclusions, cont.
Dermatologic Procedures:
 Aspirin probably does not increase clinically
important bleeding with dermatologic
procedures (six Class II studies).
©2013 American Academy of Neurology
Conclusions, cont.
EMG:
 AP therapy (aspirin or clopidogrel, or both) might
not increase clinically important bleeding with
EMG (one Class II study).
©2013 American Academy of Neurology
Conclusions, cont.
Endoscopic Procedures:
 Continued aspirin use might not increase clinically
important bleeding during transbronchial lung biopsy
(one Class II study). Although clopidogrel might
increase use of procedural strategies to control
bleeding during transbronchial lung biopsy, one study
(Class II) lacked the statistical precision to support or
exclude increased clinically important bleeding with
clopidogrel continuation.
 Continued aspirin use might not increase clinically
important bleeding with colonoscopic polypectomy
(one Class II study, three Class III studies), upper
endoscopy and polypectomy (one Class II study), or
sphincterotomy (one Class II study, one Class III
study).
©2013 American Academy of Neurology
Conclusions, cont.
Urologic Procedures:
 Aspirin probably does not increase clinically
important bleeding with transrectal ultrasound
(TRUS)-guided prostate biopsy (two Class II
studies, pooled risk difference 0, 95% CI -0.47% to
0.47%). In one Class I study and one Class III
study, aspirin did not increase transfusion,
readmission, or reoperation requirements peritransurethral resection of the prostate (TURP).
However, the studies lacked the statistical
precision to exclude clinically important increased
bleeding risks with aspirin continuation.
©2013 American Academy of Neurology
Conclusions, cont.
Spinal or Epidural Anesthesia/Pain Procedures:
 Aspirin probably does not increase clinically
important bleeding with spinal/epidural
anesthesia/pain procedures (two Class II studies).
©2013 American Academy of Neurology
Conclusions, cont.
Orthopedic Procedures:
 Whereas the results of four Class II studies and one
Class III study of aspirin use and hip surgeries vary, the
direction of the 95% CIs suggests that aspirin
probably increases blood loss or transfusion, or both.
 Statistical precision was insufficient to draw
conclusions regarding clopidogrel use in patients
undergoing hip fracture surgery (one Class II study,
one Class III study) and other nonelective orthopedic
procedures (one Class III study).
 Aspirin probably does not result in clinically important
bleeding with carpal tunnel syndrome surgery (two
Class II studies).
©2013 American Academy of Neurology
Conclusions, cont.
Other Procedures:
 When studies lumping various procedures are
considered, aspirin users probably have no increased
risk of clinically important bleeding (one Class I study,
one Class II study). How this should guide clinical
practice for specific procedures is unclear. When
abdominal ultrasound–guided biopsies are
considered as a group, aspirin might not increase the
risk of clinically important bleeding (one Class II study,
two Class III studies). Variations in surgeries and
methodologic approach and limited statistical
precision prevent conclusions from being made
regarding clopidogrel use in various invasive surgeries
(four Class II studies with limited statistical precision).
©2013 American Academy of Neurology
Clinical Question 2b
 What are the perioperative bleeding





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


risks of continuing anticoagulation?
Dental procedures
Ophthalmologic procedures
Dermatologic procedures
EMG
Endoscopic procedures
Urologic procedures
Spinal or epidural anesthesia/pain procedures
Orthopedic procedures
Other procedures
©2013 American Academy of Neurology
Perioperative Bleeding Risks
 Except where noted, these studies investigated
patients taking AC for a variety of indications,
including valvular heart disease, mechanical heart
valves, atrial fibrillation (primary and secondary
prevention), secondary stroke prevention, and
other prior TE disease. Known coagulopathies
and thrombocytopenia were generally
exclusionary criteria.
©2013 American Academy of Neurology
Conclusions
Dental Procedures:
 It is highly probable that warfarin does not
increase clinically important bleeding risks with
dental extractions (four Class I studies).
©2013 American Academy of Neurology
Conclusions, cont.
Ophthalmologic Procedures:
 One Class I study and one Class III study lacked the
statistical precision or details necessary to draw
conclusions regarding the bleeding risk associated
with warfarin continuation during cataract surgery.
 For patients undergoing ocular anesthesia, warfarin
probably does not increase clinically important
bleeding risks (two Class II and two Class III studies).
 Statistical precision was insufficient to make
recommendations regarding AC use during glaucoma
surgeries (one Class II study, one Class III study) and
vitreoretinal surgeries (one Class II study, one Class III
study).
©2013 American Academy of Neurology
Conclusions, cont.
Dermatologic Procedures:
 Five Class II studies provide conflicting data
regarding the effect of warfarin on bleeding
complications during dermatologic procedures.
Pooled risk of these heterogeneous studies
suggests that warfarin is associated with a small
risk difference for clinically important bleeding.
EMG:
 Warfarin might not increase clinically important
bleeding with EMG (one Class II study).
©2013 American Academy of Neurology
Conclusions, cont.
Endoscopic Procedures:
 AC might increase bleeding with colonoscopic
polypectomy, some of which is clinically
important (one Class III study of AC continuation,
one Class III study of resumption within one week
postprocedure).
©2013 American Academy of Neurology
Conclusions, cont.
Urologic Procedures:
 Warfarin might not increase clinically important
bleeding when different urologic procedures are
considered together (two Class III studies), but
data are insufficient to determine bleeding risks
for individual procedures.
©2013 American Academy of Neurology
Conclusions, cont.
Other Procedures:
 Based on one Class II study, continuing warfarin
during inguinal herniorrhaphy might result in
more self-limited hematomas but not clinically
important bleeding complications.
 Based on one Class II study, continuing warfarin
during endothermal ablation of the great
saphenous vein might result in no increased
clinically important bleeding.
©2013 American Academy of Neurology
Clinical Question 3
 If oral anticoagulation is stopped,
should bridging therapy be used?
©2013 American Academy of Neurology
Conclusions
 Whereas there is insufficient evidence to support

or refute a difference in TE events when heparin
bridging is used (versus discontinuation of oral AC
without bridging), most studies suggest that
heparin bridging is probably associated with an
increased risk of periprocedural bleeding in
general (two Class I studies, one Class II study,
one Class III study showing increased risk, with
one additional Class I study showing no
substantial increased risk).
There is insufficient evidence to support or refute
differences in TE risk between management
strategies of continuing oral AC versus heparin
bridging.
©2013 American Academy of Neurology
Conclusions, cont.
 The risk of bleeding is probably similar between
low-molecular-weight heparin bridging and AC
continuation in dental procedures (one Class I
study), although the clinical significance of this is
unclear given the evidence for AC continuation
with dental procedures described above.
©2013 American Academy of Neurology
Clinical Question 4
 If an antithrombotic agent is stopped,
what should be the timing of
discontinuation?
 Data are insufficient to support
recommendations.
©2013 American Academy of Neurology
Clinical Context
 Aspirin and clopidogrel both have irreversible AP activity.
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Effect duration is estimated to be the time required for
platelet turnover, approximately 7 days.e1 The duration of
action of a single dose of warfarin is estimated at 2–5
days.e1
Given these numbers, it is generally recommended that
when these agents must be discontinued preoperatively,
AP agents be stopped 7–10 days, and warfarin 5 days,
preprocedure if the goal is to eliminate their effects
completely.e2
Shorter discontinuation was considered as an option in
many of the reviewed studies (i.e., allowing for partial
platelet and factor recovery), but no data exist regarding
when this may be considered.
©2013 American Academy of Neurology
Clinical Context, cont.
 In patients requiring chronic antithrombotic agents to
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prevent TE events, stopping the agents will necessarily
increase the risk of TE events, so time off the
antithrombotic agents should be minimized. Current data
addressing exact TE risks of temporarily discontinuing
antithrombotic therapy in patients with a history of
ischemic cerebrovascular disease are limited, as are data
addressing theorized rebound effects.
Clearly, it is important to consider the relative morbidity of
potential outcomes and not just their frequency. In the
perioperative setting, TE events occur infrequently, but the
associated morbidity and mortality rates are high.
In contrast, most reported bleeding outcomes are mild.
©2013 American Academy of Neurology
Clinical Context, cont.
 Decisions regarding periprocedural antithrombotic
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therapy depend on weighing these competing risks in the
context of individual patient characteristics.
For example, recurrent stroke risk may be higher in
patients with recent stroke or TIA,e3 prior large-artery
atherosclerotic stroke,e4,e5 atrial fibrillation (AF),e6 or
hypertension, or both AF and hypertension.e6
Considering patient preference is also critical. In a study
comparing preferences of patients with AF with those of
physicians, patients were willing to experience a mean of
17.4 excess-bleeding events with warfarin and 14.7
excess-bleeding events with aspirin to prevent a stroke.e7
Sample clinical scenarios for guideline application are
presented in appendix 1 of the summary guideline
document.
©2013 American Academy of Neurology
Recommendations
 It is axiomatic that clinicians managing antithrombotic
medications periprocedurally weigh bleeding risks from
drug continuation against TE risks from discontinuation at
the individual patient level, although high-quality evidence
on which to base this decision is often unavailable.
 In addition, even when evidence is insufficient to exclude a
difference in bleeding or shows a small increase in
clinically important bleeding with antithrombotic agents,
physicians may reasonably judge that the risks and
morbidity of TE events exceed those associated with
bleeding.
©2013 American Academy of Neurology
Recommendations, cont.
 Neurologists should counsel both patients taking aspirin
for secondary stroke prevention and their physicians that
aspirin discontinuation is probably associated with
increased stroke and TIA risk (Level B). Estimated stroke
risks vary across studies and according to duration of
aspirin discontinuation.
 Neurologists should counsel patients taking AC for stroke
prevention that the TE risks associated with different AC
periprocedural management strategies (continuing oral AC
or stopping it with or without bridging heparin) are
unknown (Level U) but that the risk of TE complications
with warfarin discontinuation is probably higher if AC is
stopped for ≥7 days (Level B).
©2013 American Academy of Neurology
Recommendations, cont.
 Patients taking aspirin should be counseled that aspirin


continuation is highly unlikely to increase clinically
important bleeding complications with dental procedures
(Level A). Given minimal clinically important bleeding risks,
it is reasonable that stroke patients undergoing dental
procedures should routinely continue aspirin (Level A).
Patients taking aspirin should be counseled that aspirin
continuation probably does not increase clinically
important bleeding complications with invasive ocular
anesthesia, cataract surgery, dermatologic procedures,
TRUS-guided prostate biopsy, spinal/epidural procedures,
and carpal tunnel surgery (Level B).
Given minimal clinically important bleeding risks, it is
reasonable that stroke patients undergoing these
procedures should probably continue aspirin (Level B).
©2013 American Academy of Neurology
Recommendations, cont.
 Aspirin continuation might not increase clinically


important bleeding in vitreoretinal surgery, EMG,
transbronchial lung biopsy, colonoscopic polypectomy,
upper endoscopy with biopsy, sphincterotomy, and
abdominal ultrasound–guided biopsies. Given the weaker
data supporting minimal clinically important bleeding
risks, it is reasonable that some stroke patients undergoing
these procedures should possibly continue aspirin (Level
C).
Although bleeding events were rare, TURP studies lack the
statistical precision to exclude clinically important bleeding
risks with aspirin continuation (Level U).
Patients taking aspirin should be counseled that aspirin
probably increases bleeding risks during orthopedic hip
procedures (Level B).
©2013 American Academy of Neurology
Recommendations, cont.
 Neurologists should counsel patients that there is
insufficient evidence to make recommendations regarding
appropriate periprocedural clopidogrel, ticlopidine, or
aspirin/dipyridamole management in most situations
(Level U). Aspirin recommendations cannot be
extrapolated with certainty to other AP agents.
©2013 American Academy of Neurology
Recommendations, cont.
 Patients taking warfarin should be counseled that warfarin
continuation is highly unlikely to be associated with
increased clinically important bleeding complications with
dental procedures (Level A). Given minimal bleeding risks,
stroke patients undergoing dental procedures should
routinely continue warfarin (Level A).
©2013 American Academy of Neurology
Recommendations , cont.
 Patients taking warfarin should be counseled that warfarin

continuation is probably associated with only a small
(1.2%) increased risk difference for bleeding during
dermatologic procedures on the basis of a meta-analysis
of heterogeneous and conflicting studies (Level B). Thus,
patients undergoing dermatologic procedures should
probably continue warfarin (Level B).
Patients taking warfarin should be counseled that warfarin
continuation is probably not associated with an increased
risk of clinically important bleeding with ocular anesthesia
(Level B). However, AC practices during ophthalmologic
procedures may be driven by the postanesthesia
procedure.
©2013 American Academy of Neurology
Recommendations, cont.
 Warfarin might be associated with no increased clinically
important bleeding with EMG, prostate procedures,
inguinal herniorrhaphy, and endothermal ablation of the
great saphenous vein. Thus patients undergoing these
procedures should possibly continue warfarin (Level C).
 Although bleeding events were rare, ophthalmologic
studies (other than those regarding ocular anesthesia) lack
the statistical precision to exclude clinically important
bleeding risks with warfarin continuation. Thus, there is
insufficient evidence to make practice recommendations
regarding warfarin discontinuation in ophthalmologic
procedures (Level U).
©2013 American Academy of Neurology
Recommendations, cont.
 Patients taking warfarin should be counseled that warfarin
continuation might increase bleeding with colonoscopic
polypectomy (Level C). Thus, patients undergoing this
procedure should possibly temporarily discontinue
warfarin (Level C).
 Neurologists should counsel patients that there is
insufficient evidence to make recommendations regarding
appropriate periprocedural management of non-warfarin
oral AC (Level U). Warfarin recommendations cannot be
extrapolated with certainty to other AC agents.
©2013 American Academy of Neurology
Recommendations, cont.
 There is insufficient evidence to determine differences in
TE in chronically anticoagulated patients managed with
heparin bridging therapy relative to oral AC
discontinuation or continuation.
 Patients taking warfarin should be counseled that bridging
therapy is probably associated with increased bleeding
risks in procedures in general relative to AC cessation
(Level B).
©2013 American Academy of Neurology
Recommendations, cont.
 Bridging probably does not reduce clinically important
bleeding relative to continued AC with warfarin in
dentistry, but bleeding risk differences between patients
managed with continued warfarin versus bridging therapy
in other procedures are unknown.
 Given that the benefits of bridging therapy are not
established and that bridging is probably associated with
increased bleeding risks, there is insufficient evidence to
support or refute bridging therapy use in general (Level U).
©2013 American Academy of Neurology
Future Research
Recommendations
This review highlights limitations in the data related to
TE risks in the context of antithrombotic agent
discontinuation, theorized rebound effects of
antithrombotic medication discontinuation, bleeding
risks in invasive procedures, and bleeding risks of some
minimally invasive but common procedures.
 Large-scale prospective observational registries of patients

receiving antithrombotic agents (whether used
individually or in combination) and undergoing minor and
major surgical procedures are needed to better define
discontinuation risks. Registries should include patients
receiving different strategies to highlight various potential
risks.
Studies with long-term disability and quality of life
endpoints are needed to help understand the relative
impacts of bleeding and TE complications.
©2013 American Academy of Neurology
Future Research
Recommendations, cont.
 In minor procedures lacking sufficient evidence, such as
endoscopy with regard to AC use, randomized, controlled
trials (RCTs) of antithrombotic agent continuation versus
cessation are needed to better define bleeding risks.
 When medications must be stopped, RCTs identifying
specifically defined relative bleeding and TE risks associated
with different durations of discontinuation are needed to
inform the risk–benefit analysis.
 RCTs assessing the need for bridging therapy, associated risks,
and the ideal method of heparin administration are needed.
 Similar studies involving newer ACs such as oral direct
thrombin inhibitors and factor Xa inhibitors should be
performed.
©2013 American Academy of Neurology
References
 e1. Repchinsky C, ed. Compendium of Pharmaceuticals and Specialties, 2009
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antithrombotic therapy: American College of Chest Physicians evidence-based
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e3. Dennis M, Bamford J, Sandercock P, Warlow C. Prognosis of transient
ischemic attacks in the Oxfordshire Community Stroke Project. Stroke
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e4. Lovett JK, Coull AJ, Rothwell PM. Early risk of recurrence by subtype of
ischemic stroke in population-based incidence studies. Neurology
2004;62:569–573.
e5. Purroy F, Montaner J, Molina CA, Delgado P, Ribo M, Alvarez-Sabin J.
Patterns and predictors of early risk of recurrence after transient ischemic
attack with respect to etiologic subtypes. Stroke 2007;38:3225–3229.
e6. Lai SM, Alter M, Friday G, Sobel E. A multifactorial analysis of risk factors for
recurrence of ischemic stroke. Stroke 1994;25:958–962.
e7. Devereaux PJ, Anderson DR, Gardner MJ, et al. Differences between
perspectives of physicians and patients on anticoagulation in patients with
atrial fibrillation: observational study. BMJ 2001;323:1218–1222.
©2013 American Academy of Neurology
References, cont.
For a complete list of references, please
access the full guideline at
www.aan.com/guidelines.
©2013 American Academy of Neurology
Question-and-Answer Period
 Questions/comments?
©2013 American Academy of Neurology
Closing
 To access the complete guideline and
related guideline summary tools, visit
www.aan.com/guidelines.
 Thank you for your participation!
©2013 American Academy of Neurology