1. Management of anticoagulation and antiplatelet agents prior to endoscopy
Sushovan Guha, MD, MPhil, PhD, AGAF
Division of Gastroenterology, Hepatology, and Nutrition
UTHealth, McGovern Medical School Houston, Texas
2017 Gastroenterology and Hepatology Symposium
February 11, 2017

2. Learning objectives Recognize GI bleeding risk of antithrombotic drugs
anticoagulants (warfarin and direct oral anticoagulants or DOACs)
antiplatelets (aspirin and thienopyridines)
combination therapy
Learn strategies for high and low risk endoscopic procedures
Review MH-TMC experience in one high risk procedure

3. Why is this topic important for Gastroenterologists?
Increasing number of patients now on anti-thrombotic agents
Due to
an aging population
increased prevalence of cardiovascular disease (CVD)
improved survival
Newer anticoagulant drugs with greater efficacy prescribed now

4. Aging population

5. CVD is more prevalent in the elderly
Expected increase in antiplatelet and anticoagulant use for primary and secondary prevention
Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association
Benjamin EJ, Blaha MJ, Muntner P et al; Circulation, Jan 25, 2017, epub ahead of print

6. Reduced mortality but increased hospital discharges from CVD
Deaths due to cardiovascular diseases
Hospital discharges
Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association
Benjamin EJ, Blaha MJ, Muntner P et al; Circulation, Jan 25, 2017, epub ahead of print

7. Increased use of novel antithrombotics
National Trends in Ambulatory Oral Anticoagulant Use
Barnes GD, Goldberger ZD et al; American Journal of Medicine, 128(12): , 2015

8. Factors influencing decision
Class/type of medication
anticoagulant drugs
antiplatelet agents
Patient comorbidities
Indication for GI procedure
elective
urgent/emergency
GI bleeding
Type of GI procedure
high risk vs low risk
Patient wishes
decision must include patient in high-risk cases

9. Antiplatelet drugs (APAs)
Class/Type
Drug
Duration of Action
Reversal
Cyclooxygenase inhibitor
Aspirin
days
Hold, platelets
Phospodiesterase Inhibitor
Dipyridamole (Persantine)
2 -3 days
Hold
Thienopyridines
Clopidogrel (Plavix)
5-7 days
Ticlodipine (Ticlid)
10-14 days
Ticagrelor (Brilinta)
3-5 days
Prasugrel (Effient) 
GPIIb/IIIa inhibitors
Abciximab (ReoPro)
24 hours
Tirofiban (Aggrastat)
4-8 hours
Hold, Hemodialysis
Eptifibatide (Integrilin)
4 hours
PAR-1 inhibitor
Vorapaxar (Zontivity)
5-13 days
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

10. Anticoagulant drugs (ACs)
Class/Type
Drug
Duration of Action
Reversal
Vitamin K antagonist
Warfarin (Coumadin)
5 days
Vitamin K, PCC (prothrombin complex concentrate)
Heparin & derivatives
Unfractionated Heparin
IV 2-6 h
Protamine Sulfate
SQ h
LMWHs (low molecular weight heparins):
Enoxheparin (Lovenox)
Dalteparin (Fragmin)
24 h
Protamine sulfate, recombinant factor VIIa
Fondaparinux (Arixtra)
36 – 48 h
Direct Factor Xa inhibitor (oral)
Rivaroxoban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Savaysa)
1-4 days*
(*depends on eGFR)
Charcoal (if last intake within 2-3 hours),
nonactivated PCC or activated PCC
Direct Thrombin inhibitor
Oral: Dabigatran (Pradaxa)
1-6 days*
Idarucizumab§
IV: Desirudin (Iprivask)
PCC, Hemodialysis
Idarucizumab | Dagibatran antidote, FDA approved. For life threating bleeding and prior to emergency procedures
Fondaparinux is factor Xa inh.
* - Depends on Kidney function/GFR => Stoppage must be calculated accordingly § New FDA approved antidote LMWH : Low molecular Weight Heparins, PCC:prothrombin complex concentrate
Table Modified from The management of antithrombotic agents for patients undergoing GI endoscopy. ASGE Standards of Practice Committee Gastrointest Endosc Jan;83(1):3-16. doi: /j.gie Epub 2015 Nov 24.
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

11. Risk of thromboembolism vs Risk inherent in the procedure
To hold or not to hold
Delays procedure
Longer in-hospital stay and costs
Increased risk of cardiovascular complications
Thromboembolic events
Increased risk of Post procedural Bleeding
Hold
Continue
Considerations:
Risk of thromboembolism vs Risk inherent in the procedure

12. Risk of Thromboembolism
Determined by CHA2DS2-VASc scoring system
Consists of
congestive heart failure
hypertension
age ≥75 years [doubled]
diabetes
stroke/transient ischemic attack/thromboembolism [doubled]
vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque]
age years
sex category [female]
Useful tool for identifying “low-risk” patients, especially in the setting of AF
Assessment of the CHA2DS2-VASc score in predicting ischemic stroke, thromboembolism, and death in patients with heart failure with and without atrial fibrillation
Melgaard L, Lip GYH et al; JAMA; 314(10): , 2015

13. CHA2DS2-VASc score and CVA risk
Patients with score ≥ 2 are frequently prescribed an anticoagulant
Assessment of the CHA2DS2-VASc score in predicting ischemic stroke, thromboembolism, and death in patients with heart failure with and without atrial fibrillation
Melgaard L, Lip GYH et al; JAMA; 314(10): , 2015

14. High Risk Patients Drug eluting stents ≤ 12 months old
Bare metal coronary stents
without ACS ≤ 1 month old
with history of ACS, ≤ 12 months old
Older stents cannot be forgotten
if prior history of stent thrombosis present
second stent has an occlusion rate of 0.6 %/year x 3 years, even with continued ACs and APAs
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

15. High Risk Patients Patients with ACS or STEMI h/o multi-vessel PCI
diffuse coronary artery disease
renal failure
h/o venous thromboembolism (VTE)
mechanical heart valves (but not bio-prosthetic valves, which are low risk)
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

16. GI Procedures
High risk
Low risk

17. High Risk Procedures Polypectomy Biliary or pancreatic sphincterotomy
Treatment of varices
Percutaneous endoscopic gastrostomy (PEG) placement
Therapeutic balloon-assisted enteroscopy
EUS with FNA
Endoscopic hemostasis
Tumor ablation
Cystgastrostomy
Ampullary resection
Endoscopic mucosal resection (EMR)
Endoscopic submucosal dissection (ESD)
Pneumatic or bougie dilation
Percutaneous endoscopic jejunostomy (PEJ) placement
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

18. Low Risk Procedures
Diagnostic (EGD, colonoscopy, flexible sigmoidoscopy)
including mucosal biopsy
ERCP
with stent (biliary or pancreatic) placement
or papillary balloon dilation without sphincterotomy
Push enteroscopy
Diagnostic balloon-assisted enteroscopy
Capsule endoscopy
Enteral stent deployment (controversial)
EUS without FNA
Argon plasma coagulation
Barrett’s ablation
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

19. Exceptions PEG on aspirin or clopidogrel therapy is low risk
[not applicable to dual antiplatelet therapy (DAPT)]
EUS-FNA of solid masses on ASA/NSAIDs (low risk)
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

20. Tips to avoid post-polypectomy bleeding
Usage of cold snare for polyps <5 mm
Lift lesion using saline in large lesions
Prophylactic clip placement for polyps >10 mm
Avoid cautery to prevent late bleeding from sloughed eschar

21. ASGE Guidelines APAs Elective Procedure Anti-Coagulants
Emergency Procedure
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

22. Elective Procedures on APAs
Aspirin & NSAIDs (low Dose)
Thienopyridines (Clopidogrel, Ticlopidine)
Low risk
procedures
Continue
High risk procedures
Discontinue x 5-7 days prior
or switch to bridge therapy
If patient has recently placed coronary stent and/or ACS
Defer procedure until minimum anticoagulation completed
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

23. Elective procedures on Anticoagulants
Any short-term anticoagulation therapy
Defer procedure
Warfarin and DOAC
High thrombosis risk
High risk procedure
Bridge therapy
Low thrombosis risk
Stop for prescribed period
Low risk procedure
Continue
*Low quality of evidence
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

24. Elective procedures on Anticoagulants: How to restart treatment
Active bleeding present
Delay reinitiation till hemostasis achieved
If delay >12 – 24 h
Consider Thromboprophylaxis, Bridge therapy
No active bleeding present
Restart warfarin on same day
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

25. Emergency Procedures on APAs
Significant GI bleeding
High thrombosis risk patients
Stop only after consultation with prescribing physician
Life threatening GI
bleeding
Withhold after discussion with cardiologist
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

26. Emergency procedures on anticoagulants
Active bleeding present
Delay reinitiation till hemostasis achieved
Life threatening bleeding
INR <2.5
Do not delay procedure
Warfarin
4-Factor PCC + Vit K *ACCP recommended
Fresh Frozen Plasma
After hemostasis achieved endoscopically
Start UFH for rapid onset
Reinitiate previous medication
The management of antithrombotic agents for patients undergoing GI endoscopy, ASGE Standards of Practice Committee
Acosta RD, DeWitt JM et al; Gastrointestinal Endoscopy;83(1):3-16, 2016

27. Bridge Therapy Condition Associated diagnosis Management AF None
CHA2DS2-VASc score < 2
No bridge recommended
Mechanical valves
History of CVACHA2DS2-VASc score ≥ 2
Bridge therapy recommended
Valvular heart disease
Bileaflet mechanical AVR
Older-generation mechanical AVR (aortic valve replacement)
Mechanical AVR and any thromboembolic risk factor
Mechanical mitral valve replacement (MVR)
2014 AHA/ACC guideline for the management of patients with valvular heart disease:
a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
Nishimura RA, Thomas JD et al; Circulation; 129:e521–643, 2014

28. Nishimura RA, Thomas JD et al; Circulation; 129:e521–643, 2014
Bridge Therapy
Used in patients on Warfarin to reduce the risk of thromboembolic events
UFH and LMWH (enoxaparin) are most commonly used due to sorter onset and duration of action
However, evidence in support of this is not strong
2014 AHA/ACC guideline for the management of patients with valvular heart disease:
a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
Nishimura RA, Thomas JD et al; Circulation; 129:e521–643, 2014

29. Veitch AM, Dumonceau J-M et al; Gut;65:374–389, 2016
British Guidelines
Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines
Veitch AM, Dumonceau J-M et al; Gut;65:374–389, 2016

30. Veitch AM, Dumonceau J-M et al; Gut;65:374–389, 2016
British Guidelines
Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines
Veitch AM, Dumonceau J-M et al; Gut;65:374–389, 2016

31. Memorial Hermann – Texas Medical Center Experience
High volume tertiary care center: >300 PEGs per year
Data analyzed on
962 PEGs from 2012 to 2015
595 males and 367 females (M:F::1.6:1)
795 patients (85%) were on uninterrupted anticoagulant therapy during the procedure
Guha S, Thosani N et al, submitted to DDW 2017, unpublished

32. Age profile Age at Procedure Youngest: 18 Oldest: 97
Average age: 64.24
Median age: 66
Guha S, Thosani N et al, submitted to DDW 2017, unpublished

33. Comorbidities
Guha S, Thosani N et al, submitted to DDW 2017, unpublished

34. Complication Rates Number of Cases Percentage (out of 962)
Number of Cases
Percentage (out of 962)
In-hospital all-cause mortality 59
6.1%
30 day all-cause mortality 37
3.8%
Major Complications
Pull out 20
2.08%
PEG site infections 18
1.87%
Significant bleeding 3
0.31%
Perforation 1
0.10%
PEG related mortality
Minor Complications
Periostomal pain 21
2.18%
Leakage 16
1.66%
Any complication(s) 60
6.24%
Guha S, Thosani N et al, submitted to DDW 2017, unpublished

35. Clinically significant bleeding
Results
Drug/Therapy
Number of patients
Clinically significant bleeding
Aspirin
393
Clopidogrel
119
Aspirin and Clopidogrel 92
Heparin (IV + SC)
723 3
Warfarin 39
DOAC 10
No Anti Coagulation
167 0*
* No statistically significant difference as compared to anticoagulant or antiplatelet agents
Guha S, Thosani N et al, submitted to DDW 2017, unpublished

36. Conclusion
High risk endoscopic procedures including PEG can be performed without interrupting anticoagulants and antiplatelet agents
if performed in a high volume center by experienced gastroenterologists
especially important in the elderly

37. Thank You