Management of Agents in Endoscopy

Daniel Raines, MD FACG Chief of Gastroenterology LSU Health Sciences Center Presentation Overview

• Antithrombotic agents encountered by endoscopists • Risks of cardiovascular events associated with specific conditions • Risks of endoscopy in the setting of antithrombotic therapy • Recommendations for management of antithrombotic agents in the setting of acute gastrointestinal bleeding as well as elective endoscopy Antithrombotic Agents

Antiplatelets

Aspirin (Coumadin)

Thienopyridines Direct Acting Oral - (Plavix) Anticoagulants (DOAC’s) - (Effient) - (Pradaxa) - (Brilinta) - (Eliquis) - (Ticlid) - (Xarelto) - (Savaysa)

*all of these agents, except apixiban, are associated with an increased risk of GI bleeding* Antiplatelet Agents

Aspirin • Inhibits aggregation by inhibition of cyclooxygenase • Effective for prevention of cardiovascular events in a variety of settings

Withdrawal of aspirin precipitates up to 10% of acute vascular events • 14 days prior to • 8 days prior to acute coronary syndrome • 26 days prior to peripheral ischemia

Burger W. J Intern Med 2005;257:399-414. Discontinuation of Aspirin in Patients with Coronary Disease and Peptic Ulcers

14

12

10

8

6

4

2

0 30 day Rebleeding 30 day Mortality

Asprin Placebo 30 day risk of rebleeding is twice as high (10% vs 5%) but 30 day morality increases 10 fold (1.3% vs 13%) Sung, et al. Ann Int Med 2010. Antiplatelet Agents

Thienopyridines • Bind the platelet receptor to inhibit activation • Commonly indicated in the management of coronary, cerebrovascular and peripheral vascular disease • Duration of action varies: Clopidogrel (Plavix) 5-7 days Prasugrel (Effient) 5-7 days Ticagrelor (Brilinta) 3-5 days Ticlopidine (Ticlid) 10-14 days Anticoagulants

Warfarin (Coumadin) • Inhibits vitamin K-dependent clotting factors (II, VII, IX, X) and proteins C,S • Commonly indicated for prevention of stroke in patients with atrial fibrillation, valvular heart disease or venous thrombosis • Therapeutic effect in 3-5 days • INR corrects after ~5 days of interruption Anticoagulants

Direct Oral Acting Anticoagulants (DOAC’s) • Inhibitors Dabigatran (Pradaxa) • Factor Xa Inhibitors Apixaban (Eliquis) Rivaroxaban (Xarelto) Edoxaban (Savaysa) Anticoagulants

Direct Oral Acting Anticoagulants (DOAC’s) • Indications similar to warfarin with comparable efficacy • Rapid onset of action (1-3 hours) • Coagulation normalizes in ~48 hours after drug withdrawal*

*with renal failure, effect may persist for 3 days (CrCl 30-59) or 4 days (CrCl 15-29)* Risks of Cardiovascular Event

• Acute MI following acute coronary syndrome or coronary stent placement

• Stroke in Atrial Fibrillation

• Thromboembolism with Valvular Heart Disease Antiplatelet Therapy for Coronary Events

• Dual Antiplatelet Therapy (DAPT) = Aspirin plus a Thienopyridine • DAPT is commonly indicated for coronary disease 30 days post LHC with bare metal stent 90 days post acute coronary syndrome 180 days post LHC with drug-eluting stent

*risk of AMI is high if DAPT is interrupted during these time periods* Stroke Risk in Atrial Fibrillation

CHA2DS2-VASc Score Risk Element Score Congestive Heart Failure 1 Point Hypertension 1 Point Age 65-74 1 Point Age >75 2 Points Diabetes Mellitus 1 Point Female Sex 1 Point Prior Stroke 2 Points Vascular Disease 1 Points CHA2DS2-VASc Score

Score Risk of stroke (CVA) % Risk of annual CVA 0 Low 0 1 Intermediate 1.3 2 Intermediate 2.2 3 High 3.2 4 High 4.0 5 High 6.7 6 High 9.8 7 High 9.6 8 High 6.7 9 High 15.2 Thromboembolic Risk

Risk Group Mechanical Heart Atrial Fibrillation Venous Valve Thromboembolism (VTE)

High Mitral Valve CHA2DS2-VASC >5 VTE <3 months prior

Moderate Bi-leaflet Aortic Valve CHA2DS2-VASC 3-4 VTE 3-12 months prior with HTN, DM, CHF, or Afib Recurrent VTE

Low Bi-leaflet Aortic Valve CHA2DS2-VASC <2 VTE >12 months prior with no other risk factors

2012 American College of Chest Physicians (ACCP) Guideline Acute Gastrointestinal Bleeding

General Recommendations • Hold antithrombotic agents for active bleeding until hemostasis is achieved *drug effect will persist to provide protection while planning endoscopy* • Laboratory evaluation for anticoagulants Prothrombin time (PT) for warfarin, rivaroxaban and apixaban Partial thromboplastin time (PTT) for dabigatran Acute Gastrointestinal Bleeding

Reversal of Warfarin • Do not delay endoscopy if INR <2.5 • Use Prothrombin Complex (factors II,VII, IX,X) to correct INR • May also use Vitamin K (5-10mg IV) but use caution in valvular hear disease

*FFP is not recommended due to slow correction and risk of pulmonary edema*

Acosta RD et al. Management of Antithrombotic Agents. GIE 2016 (83):1 Acute Gastrointestinal Bleeding

Reversal of DOACs • Idarucizumab (Praxbind) – monoclonal antibody for dabigatran • Andexanet alfa – recombinant protein designed to reverse all Factor Xa inhibitors (rivaroxaban, apixaban, edoxaban)

Pollack CV. N Eng J Med 2015;373 (6):511-520 Siegal DM. N Eng J Med 2015;373:2413-2424 Acute Gastrointestinal Bleeding

Resumption of • Resume aspirin immediately after hemostasis is achieved • Resume thienopyridine therapy immediately if high risk (ex: recent stent) or within 7 days if low risk • Resume anticoagulants 24-48 hours depending on indication *discuss with cardiology* Risks of Endoscopy

Low-risk procedures Higher-risk procedures

• Diagnostic EGD and colonoscopy including mucosal • Polypectomy biopsy • Endoscopic hemostasis • Stricture dilation • Argon plasma coagulation • PEG placement • Capsule endoscopy • Biliary or pancreatic • ERCP with stent placement sphincterotomy without sphincterotomy • EMR • EUS without FNA • EUS with FNA

Acosta RD et al. Management of Antithrombotic Agents. GIE 2016 (83):1 High Risk Procedures

Antiplatelet Therapy • Aspirin prescribed for a specific indication should not be held prior to or after endoscopy • Thienopyridine agents should be held for 5 days prior to high risk procedures except in patients on DAPT for recent MI or stent *bridge with aspirin if on monotherapy Polypectomy with Thienopyridines

Singh et al (2010) • 1681 patients (142 taking clopidogrel) • Post-polypectomy bleeding 3.5% with clopidogrel vs 1.0% in controls

Feagins et al (2013) • 516 patients (219 taking thienopyridines) • Immediate bleeding: 7.3% with thienopyridine group vs 4.7% in controls • Delayed bleeding: 2.4% in the thienopyridine group vs 0% in controls

Singh M. Gastrointest Endo 2010;71:998-1005. Feagins LA. Clin Gastroenterol Hepatol 2013;11:1325-32. High Risk Procedures

Anticoagulants • Warfarin: hold for 5 days In patients at high risk for a cardiovascular event, consider an enoxaparin (Lovenox) bridge

• DOACs: hold for 2 days In patients with a CrCl <60, it may take 3-4 days for coagulation to normalize Bridging is not recommended for DOACs if dosed properly Bridge Therapy for Warfarin

Condition Associated diagnosis Management

Atrial Fibrillation CHA2DS2-VASc score < 2 No bridge recommended

CHA DS -VASc score ≥ 2 2 2 Bridge therapy Mechanical valves recommended History of CVA

Valvular heart disease Bileaflet mechanical AVR No bridge recommended

Mechanical AVR and any thromboembolic risk factor Bridge therapy recommended Mechanical mitral valve replacement Bleeding after Polypectomy <1cm in Anticoagulated Patients

23 25

20

14 15

10 5

5 0

0 Immediate Bleeding Delayed Bleeding Cold Hot Hot snare is associated with increased risk compared to cold snare in both immediate (23%) and delayed (14%) bleeding Cold snare polypectomy for polyps <1cm may be safe in the setting of anticoagulation Horiuchi A. Gastrointest Endosc 2014;79(3):417-23. Summary Recommendations

• Do not hold aspirin before or after endoscopy except in cases of active bleeding or lack of indication • Do not interrupt DAPT during the minimum treatment time period following ACS or coronary stent • Do suspend thienopyridine or therapy when appropriate for high risk endoscopic procedures Additional Recommendations

• Print tables from the ASGE Guidelines and ACC Recommendations for your office and endoscopy unit • Prior to modifying a patient’s antithrombotic therapy, discuss the risks and benefits of these modifications and document your discussion in the medical record References

2016 ASGE Guideline for Management of Antithrombotic Agents

2016 American College of Cardiology Consortium (3rd) Recommendations

Acosta RD et al. Management of Antithrombotic Agents. GIE 2016 (83):1