Gastrointest Interv 2012; 1:58–62

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Gastrointestinal Intervention
journal homepage: www.gi-intervention.org

Review Article

Current guidelines for endoscopy in patients receiving antithrombotic medication

Christopher J.L. Khor*, Juanda L. Hartono

a b s t r a c t

Antiplatelet agents and anticoagulants make up the larger group of antithrombotic medications, which have seen increasing use worldwide as
populations in developed countries age, and ischemic heart disease prevalence rises. Antithrombotic medications reduce the risk of thrombo-
embolic events in susceptible individuals, but increase the risk of gastrointestinal bleeding. Cessation of antithrombotic drugs prior to endoscopic
therapy has been proposed, aimed at reducing the risk of immediate and early bleeding. However, interruption of antithrombotic therapy is
associated with cardiovascular risk. The peri-endoscopic management of patients at high thromboembolic risk therefore requires knowledge of
both the bleeding risk associated with endoscopic procedures, and the potential risks of stopping antithrombotic therapy. Three major endoscopy
organizations (British Society of Gastroenterology, American Society of Gastrointestinal Endoscopy & European Society of Gastrointestinal
Endoscopy) have published guidelines aimed at providing a rational strategy for the endoscopist in managing the individual patient on antith-
rombotic medication. This article compares and contrasts the approach of each guideline, in an attempt at consensus. The British Society of
Gastroenterology and American Society of Gastrointestinal Endoscopy guidelines address the use of both antiplatelet agents and anticoagulants
during the peri-endoscopic period, while the European Society of Gastrointestinal Endoscopy guideline is focused solely on antiplatelet medica-
tion. The guidelines were formulated with reference mainly to observational studies and expert opinion, and therefore have a limited basis in
evidence. A rational strategy is proposed for common scenarios encountered in gastrointestinal endoscopy, based on the published guidelines.
Despite the existence of these guidelines, they serve at best as a framework for individualized management tailored to the patient’s particular
clinical scenario.
Copyright Ó 2012, Society of Gastrointestinal Intervention. Published by Elsevier. All rights reserved.

Keywords: Antiplatelet, Aspirin, Gastrointestinal endoscopy, Thienopyridine, Warfarin bleeding

Introduction associated with cardiovascular risk; it has been estimated that

Antiplatelet agents and anticoagulants make up the larger group
of antithrombotic medications. These drugs have seen increasing
use worldwide as populations in developed countries age, and
ischemic heart disease prevalence rises. The antiplatelet agents are
comprised of aspirin, the non-steroidal anti-inflammatory drugs
(NSAIDs), the thienopyridines (e.g., clopidogrel, prasugrel & ticlo-
dipine) and the glycoprotein IIb/IIIa receptor inhibitors. Anticoag-
ulants include, warfarin, heparin and the low-molecular-weight
heparins.
Antithrombotic medications reduce the risk of thromboem-
bolic events in susceptible individuals, but increase the risk of
gastrointestinal bleeding.1 Cessation of antithrombotic drugs
prior to endoscopic therapy has been proposed in a number of
studies, aimed at reducing the risk of immediate and early
bleeding. Interruption of antithrombotic therapy is however
about 5% of hospitalizations for acute coronary syndrome are
due to discontinuation of antiplatelet therapy in patients
undergoing a non-cardiovascular procedure.2 The peri-
endoscopic management of patients at high thromboembolic
risk therefore requires knowledge of both the bleeding risk
associated with endoscopic procedures, and the potential risks
of stopping antithrombotic therapy.3
The guidelines
Three major endoscopy organizations have published guidelines
aimed at providing a rational strategy for the endoscopist in
managing the individual patient on antithrombotic medication.
This paper will compare and contrast the approach of each guide-
line, in an attempt at consensus.

Department of Gastroenterology & Hepatology, National University Hospital, 1E Kent Ridge Rd, NUHS Tower Block, Level 10, Singapore 119228, Singapore
Received 10 September 2012; Revised 23 September 2012; Accepted 24 September 2012
* Corresponding author. Department of Gastroenterology & Hepatology, National University Hospital, 1E Kent Ridge Rd, NUHS Tower Block, Level 10, Singapore 119228,
Singapore.
E-mail address: christopher_khor@nuhs.edu.sg (C.J.L. Khor).

2213-1795/$ – see front matter Copyright Ó 2012, Society of Gastrointestinal Intervention. Published by Elsevier. All rights reserved.
http://dx.doi.org/10.1016/j.gii.2012.09.003
 Christopher J.L. Khor and Juanda L. Hartono / Endoscopy and antithrombotic medication 59

The published guidelines, in chronological order of publication, Table 2 Thrombosis Risk Stratification for Discontinuation of Clopidogrel
are: (1) “Guidelines for the management of anticoagulant and
Low risk for Coronary DES >12 mos previously
antiplatelet therapy in patients undergoing endoscopic proce-
thrombosis Bare metal coronary stents inserted >6
dures” published by the British Society of Gastroenterology (BSG) in wks previously without associated risk factors
20084; (2) “Management of antithrombotic agents for endoscopic Stroke without cardiac failure >6 wks previously
procedures”, which is an update of two guidelines and was pub- Ischemic heart disease without coronary stents
Cerebrovascular disease
lished by the American Society of Gastrointestinal Endoscopy:
Peripheral vascular disease
(ASGE) in 20095; and (3), “Endoscopy and antiplatelet agents” by High risk for Coronary DES inserted 12 mos previously
the European Society of Gastrointestinal Endoscopy (ESGE) pub- thrombosis Bare metal coronary stents inserted 6 wks
lished in 2011.2 previously or >6 wks previously with
The BSG and ASGE guidelines address the use of both anti- associated risk factors
Stroke 6 wks previously
platelet agents and anticoagulants during the peri-endoscopic
Acute coronary syndrome
period, while the ESGE guideline is focused solely on antiplatelet Non-stented percutaneous coronary
medication. All three guidelines stratify the risk of bleeding by intervention after myocardial infarction
procedure type (low vs. high bleeding risk) and the risk of throm- DES, drug-eluting stents. Adapted from ESGE, BSG and ASGE guidelines.
boembolic events (low vs. high risk) arising from discontinuation of
therapy. It is noteworthy that these guidelines were formulated
with reference mainly to observational studies and expert opinion, (APC) hemostasis. Table 1 summarizes bleeding risk stratified by
and many of the recommendations made therefore have a limited type of endoscopic procedure. Tables 2 and 3 stratify cardiovascular
basis in evidence. conditions by thromboembolic risk when antiplatelet agents and
The guidelines also vary by the depth into which specific anticoagulant therapy are discontinued, respectively.
endoscopic procedures are discussed with respect to associated
bleeding risk. The BSG does not discuss individual procedures. The Procedures at low risk of peri-endoscopic bleeding
ASGE discusses diagnostic endoscopy, colonic polypectomy, endo-
scopic sphincterotomy and percutaneous endoscopic gastrostomy All three guidelines are in agreement that aspirin is to be
(PEG). The ESGE guideline carries the most detailed discussion of continued. The BSG and ASGE recommend continuing thienopyr-
the bleeding risks associated with all the procedures highlighted by idines. The ESGE however recommends stopping the thienopyr-
the ASGE, but in addition reviews endoscopic mucosal resection idines for these particular scenarios although they are deemed
(EMR) and endoscopic submucosal dissection (ESD), EUS-FNA, “low-risk” for bleeding: removal of subcentimeter colonic polyps,
endoscopic stent placement and dilation, device-assisted entero- stricture dilation, enteral stent placement, APC and EUS-FNA of
scopy, endoscopic variceal ligation, and argon plasma coagulation solid lesions. Except for enteral stent placement (ASGE), these are
considered high-risk procedures by the other two societies. For
Table 1 Bleeding Risk Stratified by Type of Endoscopic Procedure anticoagulants, BSG and ASGE guidelines advocate continuation at
therapeutic international normalized ratio (INR).
Bleeding risk Type of procedure Guideline where risk
is specified
Low risk for Diagnostic EGD, colonoscopy ASGE, BSG and ESGE Procedures at high risk of peri-endoscopic bleeding
bleeding (including biopsy)
Colonic polypectomy <1 cm ESGE In the main, these are procedures involving endoscopic
ERCP without sphincterotomy ASGE, BSG and ESGE
resection and cautery, plus procedures with the potential to
EUS without FNA ASGE, BSG and ESGE
EUS-FNA of solid masses ESGE
induce bleeding that is inaccessible to endoscopic therapy. The
Stricture dilation ESGE three guidelines each dichotomize the approach between
Digestive stenting ASGE, BSG and ESGE conditions at low thromboembolic risk, and those at high
Argon plasma coagulation ESGE thromboembolic risk, with respect to use of aspirin, thienopyr-
Diagnostic enteroscopy and ASGE
idines and anticoagulants (the ESGE guideline deals only with
balloon-assisted enteroscopy
Capsule endoscopy ASGE antiplatelet agents). The general recommendation with regards
High risk for ERCP with sphincterotomy, ASGE, BSG and ESGE to low thromboembolic risk conditions is to stop the therapy
bleeding with or without balloon concerned before endoscopy (thienopyridine 5–7 days before,
papillary dilation
Polypectomy All in ASGE and
BSG; >1 cm in ESGE Table 3 Thromboembolic Risk Stratification for Discontinuation of Anticoagu-
Stricture dilation ASGE, BSG lant Therapy
Variceal therapy ASGE, BSG and ESGE
PEG placement ASGE, BSG and ESGE Low risk for Prosthetic metal heart valve in aortic position
Endoscopic hemostasis ASGE thromboembolism Bioprosthetic valve
EUS with FNA All in ASGE, BSG; Atrial fibrillation without valvular disease
cystic lesions only, Venous thromboembolism >3 mos previously
in ESGE High risk for Prosthetic metal heart valve in mitral position
Cyst-enterostomy ASGE, BSG and ESGE thromboembolism Prosthetic heart valve and atrial fibrillation
Tumor ablation – any technique ASGE Prosthetic heart valve in any position and
EMR, ESD and ampullary ESGE, BSG previous thromboembolic event
resection Atrial fibrillation with valvular heart disease,
EMR ASGE prosthetic valves, active congestive heart
failure, left ventricular ejection fraction of
ASGE, American Society of Gastrointestinal Endoscopy; BSG, British Society of
< 35%, a history of a thromboembolic event,
Gastroenterology; EGD, Esophago-Gastro-Duodenoscopy; EMR, endoscopic
hypertension, diabetes mellitus, or age >75 ys
mucosal resection; ERCP, endoscopic retrograde cholangiopancreatography; ESD,
Venous thromboembolism <3 mos previously
endoscopic submucosal dissection; ESGE, European Society of Gastrointestinal
Thrombophilia syndromes
Endoscopy; EUS, Endoscopic Ultrasound; FNA, Fine Needle Aspiration; PEG,
percutaneous endoscopic gastrostomy. Adapted from BSG and ASGE guidelines.
60 Gastrointestinal Intervention 2012 1(1), 58–62
warfarin 5 days before). For conditions associated with high
thromboembolic risk the societies advise delaying endoscopy
until the thienopyridine/dual antiplatelet therapy course has
ended, or stopping the medication temporarily in consultation
with the managing cardiologist. Consideration should also be
given to performing an alternative or temporizing procedure
associated with lower bleeding risk, if possible. Aspirin should be
maintained in all cases, or used in place of the thienopyridine.2 In
patients taking warfarin, both BSG and ASGE recommend stop-
ping warfarin 5 days before the procedure, and bridging with
low-molecular-weight heparin.
Risk of interrupting antithrombotic therapy for a procedure
at higher risk of bleeding, versus the risk of peri-endoscopic
bleeding when antithrombotic medication is continued
Prior to performing an endoscopic procedure for a patient on
antithrombotic therapy, one should first consider the risks of
a thromboembolic event related to interruption of antith-
rombotic medication, and second, bleeding related to endo-
scopic therapy while on antithrombotic medication. One should
be mindful that a thromboembolic event that may occur
following withdrawal of medication can be devastating, whereas
bleeding after high-risk procedures, although increased in
frequency, is rarely associated with significant morbidity or
mortality.5
Conditions carrying a higher risk of thromboembolic events
if antithrombotic therapy is interrupted include atrial fibrilla-
tion associated with valvular heart disease, mechanical valves
in the mitral position, and mechanical valves in patients who
have had a previous thromboembolic event. Study data indi-
cate that the absolute risk of an embolic event for patients in
whom anticoagulation is interrupted for 4 to 7 days is about
1%.6,7
Patients with coronary stents are at high risk of stent throm-
bosis when dual antiplatelet therapy is discontinued before the
minimum duration specified by the American College of Cardi-
ology (ACC); 1 year for drug-eluting stents, and 1 month for bare
metal stents.8 One large prospective study reported a hazard ratio
of 89 for stent thrombosis when antiplatelet therapy was dis-
continued prematurely.9 Case fatality is extremely high, at 20% to
45%.3,9 Patients who require dual antiplatelet therapy should
always be kept on aspirin, and the decision to discontinue the
thienopyridine should be taken in consultation with the attending
cardiologist.
The peri-endoscopic bleeding risk for patients on antith-
rombotic therapy may be considered by procedure; this review
will focus on the procedures at higher risk of bleeding for which
more evidence exists. For colonoscopic polypectomy while on
aspirin or NSAIDs, the bleeding risk appears to be small.10
Warfarin use is associated with increased bleeding risk, as is
resumption of anticoagulation within 1 week of poly-
pectomy.10,11 Several studies of prophylactic endoclip application
suggest that it keeps bleeding rates low in anticoagulated
patients, but current evidence is insufficient for its routine use to
be recommended.12,13 The risk of bleeding after endoscopic
sphincterotomy (ES) is 0.3% to 2%.14–16 Withdrawal of aspirin
does not appear to reduce this risk17; anticoagulation
with warfarin or heparin however increases the risk of post-
sphincterotomy bleeding.18 Large balloon papillary dilation in
combination with ES (to avoid mechanical lithotripsy for the
removal of large biliary calculi) is associated with higher
bleeding risk than ES alone. In PEG placement, the overall risk of
bleeding is about 2.5%,19 but the additional risk conferred by
antithrombotic therapy is not known. EMR is done less
frequently in the West than in the East; Western series report
higher bleeding rates of 4.6% to 12%. Duodenal polypectomy is
associated with higher risk of bleeding than polypectomy at
other sites, and is reported as 3.1% to 11.6% in the five most
recent prospective studies using EMR techniques. The technique
of endoscopic ampullectomy is similar to EMR, and is associated
with bleeding risk of 5.6% from five large retrospective series.2 A
recent meta-analysis showed that ESD has a two-fold risk of
bleeding when compared with EMR (OR 2.20; 95% CI, 1.58–3.07).
Antiplatelet agents and anticoagulants were routinely stopped
ahead of all studies involving these high-risk procedures.
Appendix summarizes the approach of each of the three
guidelines towards the management of antithrombotic agents
for endoscopic procedures at high risk for periprocedural
bleeding.
Urgent endoscopy in the patient with acute coronary
syndrome or a recently placed coronary stent
The ASGE guideline is the only one that discusses this
frequently-encountered scenario in depth. An estimated 1% to 3% of
patients with acute coronary syndrome (ACS) will have an associ-
ated gastrointestinal (GI) bleed, and these individuals are expected
to have a four- to seven-fold increase in the risk of in-hospital
mortality over those without GI bleeding.5 The overall risk of
peri-procedural complications associated with upper GI endoscopy
is about 1% to 2% (1% with colonoscopy),20,21 but may be as high as
12% for endoscopy done on the same day as the acute cardiac
event.22 The data in this setting however remains scanty. A decision
analysis showed that upper endoscopy before cardiac catheteriza-
tion was beneficial in patients who presented with overt GI bleed in
the setting of ACS, significantly reducing overall mortality.23 The
ASGE suggests withholding antiplatelet agents until hemostasis is
achieved, but qualifies that no strong recommendation can be
made.
Conclusion
All three guidelines stratify patients by thromboembolic risk if
antithrombotic therapy needs to be interrupted, but differ in the
detail with which they discuss the individual endoscopic proce-
dures. The ESGE guideline deals only with antiplatelet agents.
There is general agreement among them with respect to anti-
platelet therapy continuation for individuals at low risk of
thromboembolism and for continuation of anticoagulant use, but
broad differences are seen in the ESGE review of specific endo-
scopic therapies. The decision to interrupt antithrombotic
therapy has to be individualized in consideration of the patient’s
condition and procedure risks. In patients with coronary stent
placement of duration shorter than the appropriate minimum
stipulated by the ACC, the high risk of a thrombotic event with
devastating consequences mandates that the decision to inter-
rupt antiplatelet therapy is taken in consultation with the
attending cardiologist.
Conflict of Interest
The author & co-author have no conflict of interest to report.
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Appendix

62
Management of antiplatelet/anticoagulant therapy in endoscopic procedures associated with high risk of bleeding.

Procedure BSG 2008 ASGE 2009 ESGE 2011

Continue aspirin Continue TPD Continue Continue aspirin Continue TPD Continue Continue aspirin Continue TPD
warfarin warfarin
Thromboembolic risk Thromboembolic risk Thromboembolic risk

Low High Low High Low High Low High Low High Low High
Colon Yes Yes Stop TPD 7 ds Consult Stop warfarin Yesb Yes No Postpone scope No, consider Yes Yes No Yes / aspirin
polypectomya before scope cardiologist, 5 ds before bridging Use instead +
Continue consider endoscopy LMWH/UFH aspirin cardio
aspirin if stopping if High risk: consult
Pneumatic Yes Yes already beyond in addition Yesb Yes Yes Yes No
or bougie on, otherwise minimum start LMWH
dilationa consider duration for 2 ds after
EUS + FNA Yes Yes aspirin TPD therapy, stopping Yesb Yes Consider If emergent, Yes Yes No No
alone when continue warfarin continuing/starting consider Stop
TPD stopped aspirin aspirin in dual stopping and for cystic
therapy/TPD delaying for lesions
alone 7–10 ds;
for patients in consider
periendoscopic continuing/starting

Gastrointestinal Intervention 2012 1(1), 58–62

period aspirin in dual
therapy/TPD
monotherapy
patients in
the periendoscopic
period
Endoscopic Yes Yes Yesb Yes Yesc Yes 1) Stop TPD
sphincterotomy 2) use blended
current for the
extraction of
large biliary
stones in
patients
on aspirin,
mechanical
lithotripsy
recommended
over
ES+ LBD
Percutaneous Yes Yes Yesb Yes Yes Yes
endoscopic
gastrostomy
Endoscopic Yes Yes Yesb Yes Yes Yes No
variceal
ligation
Endoscopic Yes Yes Yesb Yes Yes Yes Yes (no
hemostasisa recommendation
for DAT)
EMR/ESD & Yes Yes No No No
ampullectomy (EMR only) (EMR only)
Device-assisted Yes Yes Consider
enteroscopy stopping

Note: From “Endoscopy in the patient on antithrombotic therapy,” by H Abu Daya, L Younan and AI Sharara, 2012 Curr Opin Gastroenterol 28, p.432–441. Copyright 2012, Lippincott Williams & Wilkins. Adapted with permission.
DAT, dual antiplatelet therapy; EMR, endoscopic mucosal resection; ES, endoscopic sphincterotomy; ESD, endoscopic submucosal dissection; EUS, endoscopic ultrasound; FNA, fine needle aspiration; LBD, large balloon dilation;
LMWH, low-molecular-weight heparin; TPD, thienopyridine; UFH, unfractionated heparin.
a
Colon polypectomy <1 cm, dilation of digestive stenosis, EUS with FNA of solid masses, and argon plasma coagulation (APC) are considered low-risk procedures by the ESGE. Aspirin should be continued in all these
procedures, whereas thienopyridines are to be continued only in APC of angiodysplasias according to the ESGE.
b
Consider stopping it if possible, or else can be continued.
c
If large balloon papillary dilation is to be performed then aspirin should be stopped.