1

How to Manage Antiplatelet Therapy in theHow to Manage Antiplatelet Therapy in the Peri-Endoscopic Period

Neena S. Abraham MD, MSCE, FACG

Michael E DeBakey Veterans Affairs Medical CenterMichael E. DeBakey Veterans Affairs Medical CenterSections of Gastroenterology & Health Services Research

Associate Professor of MedicineBaylor College of Medicine, Houston, TX, USA

Learning Objectives

1. To accurately assess the risk of endoscopic yprocedures in non-bleeding patients on antiplatelet therapy

2. To clarify the CV risk of modifying antiplatelet therapy in the peri-endoscopic setting

3 To understand best-practice recommendations3. To understand best practice recommendations for management in the non-urgent and urgent setting

2

Clinical Indications for Antiplatelet Therapy Use

Acute coronary syndrome (ACS) ST-segment elevation MI (STEMI)

Acute peripheral occlusion

Secondary prevention ST segment elevation MI (STEMI)

Non-ST-segment elevation MI (NSTEMI)

Coronary revascularization Percutaneous coronary

intervention (PCI)

Coronary artery bypass graft (C G)

Secondary prevention Coronary artery

disease (CAD)/ACS

CVA/TIA

Peripheral arterial disease (PAD)

Heart failure(CABG)

Acute cerebrovascularaccident (CVA)/Transient ischemic attack (TIA)

Atrial fibrillation

Mechanical valve

Antiplatelet Therapy Use in the United States: REACH Registry

Antiplatelet agents and anticoagulant (1%)

Anticoagulant only (8%)

Antiplatelet agents only (8%)

ASA plus antiplatelets and anticoag lants (1%)

ASA only (69%)

ASA and antiplatelet

agents (13%)

ASA and anticoagulants (4%)

anticoagulants (1%)

Cannon et al. Am Heart J 2010.

3

Case 1

65-year-old man with a family history of colorectal cancer

STEMI with PCI and drug-eluting stent (DES)

1. Stop ASA + clopidogrel 7-10 days prior to colonoscopy

g g ( )13 months ago

Dual antiplatelet therapy: ASA + clopidogrel (Plavix)

Asthma—Rx: Inhalers

No other comorbidities/medications

2. Stop ASA only 7-10 days prior to colonoscopy

3. Stop clopidogrel only 7-10 days prior to colonoscopy No other comorbidities/medications

Normal labs

PLAN: Elective screening colonoscopy

How should you manage his antiplatelet therapy?

colonoscopy

4. Proceed with screening exam on dual antiplatelet therapy

Endoscopic Endoscopic Bleeding RiskBleeding Risk

Thromboembolic Thromboembolic RiskRisk

4

Indication for antiplatelet therapy

Thromboembolic RiskProbability of event depends on 3 factors

Douketis JD. Thromb Res 2002.

Presence of additional thromboembolic risk

factors

Consequence of thromboembolic

event

Low- vs. High-Risk Thromboembolic Conditions

Low-Risk High-RiskUncomplicated or

paroxysmal nonvalvular

Atrial fibrillation associated with:

Valvular heart disease

atrial fibrillation

Bioprosthetic valve

Mechanical valve in the

aortic position

Deep-vein thrombosis

Prosthetic valves

Active CHF

LVEF <35%

History of thromboembolic event

Hypertension

Diabetes mellitus

Age >75 yrs

Mechanical valve in any position and

previous thromboembolic event

Recently (<1 yr) placed coronary stent

Acute coronary syndrome

Non-stented PCI after MI

Anderson et al. Gastrointest Endosc 2009.

Recently (<1 yr) placed coronary stent

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The Cardiac Patient: Indications for ASA+Clopidogrel

Up to 12 months following unstable angina or NSTEMI managed without interventionmanaged without intervention

At least 14 days (12 months in some) following STEMI

Up to 12 months after bare metal t t (BMS) l t (i PCI)

Greatest risk for thrombotic event with

cessation of antiplatelet therapy

stent (BMS) placement (i.e., PCI)

At least 12 months after DES placement (i.e., PCI)

Becker et al. Am J Gastroenterol 2009.

Stent Thrombosis: Risk of Cardiac DeathN=431 STEMI Patients, Post-PCI on Antithrombotic Therapy

30

25 3%

27.9%

e

1 in 5 patients who experience a first definite stent thrombosis experience

a second stent thrombosis.

Prevalence of early stent thrombosis (0-30 days post-PCI) ≈ 1% Varies depending on clinical procedural treatment

2018.0%

23.6%25.3%

lati

ve D

eath

Rat

e Varies depending on clinical, procedural, treatment and genetic risk factors

Late stent thrombosis (31-360 days post-PCI) more common among patients with DES (vs. BMS)

van Werkum JW et al. Circulation 2009.

10

Cu

mu

30 days 1 year 2 years 3 years

) 3-year rate = 2.9%*

Steady incidence over 3 years rate of 0.6% per year*

*Daemen J et al. Lancet 2007.

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Risk Factors for Stent ThrombosisClinical

Prior stent thrombosis

Presentation with ACS or STEMI

Procedural

Diffuse CAD

Smaller post-PCI diameterSTEMI

Multivessel PCI

Diabetes

Renal failure

BMS implantation within last 30 days or DES

diameter

Multiple stents

Residual dissection

Bifurcation stenting

Large thrombus burden

First-generation DESimplantation within last 12 months

Noncardiac surgery early after PCI

g

Becker et al. Am J Gastroenterol 2009; Sherwood et al. Curr Treatment Options Cardio Med 2010.

Risk of Clinical Events After Clopidogrel Cessation Among Patients with ACS

75.0%

PCI-Treated PatientsMedically Treated Patients

Significantly higher risk of

30.0%

45.0%

60.0%

nce

of

Dea

th o

r M

I adverse events (~2-fold increase) during first 0-90 days after

stopping clopidogrel

Ho et al. JAMA 2008.

0.0%

15.0%

Inci

den

0-90d 91-180d 181-270d

Days Post-Clopidogrel Cessation

7

Stent Thrombosis Post-DES: Risk with Antithrombotic Cessation

nti

nu

atio

n

ven

t 122 days

Short-term discontinuation of a thienopyridine is safe in patients with DES if ASA therapy is maintained.

P<0 0001

60

120

me

fro

m D

rug

Dis

con

to T

hro

mb

oti

c E

v

7 days 7 days

P<0.0001P<0.0001

Eisenberg M et al. Circulation 2009.

0Tim

ASA and thienopyridine discontinued simultaneously (n=33)

ASA discontinued after thienopyridine previously discontinued (n=15)

Only thienopyridine discontinued; ASA continued (n=94)

Patients with a Thrombotic Event

Endoscopic Bleeding Risk

Thromboembolic Thromboembolic RiskRisk

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Endoscopy-Related GI Bleeding Risks

Low Risk (<1%) High Risk (>1%)

Diagnostic + biopsy

EGD (1 0% 0 1%)

Polypectomy

G t i (7 2%)

Bleeding risk varies with procedure type and presence/absence of therapeutic interventions.

EGD (1.0%-0.1%)

Double balloon enteroscopy(0.1%)

Colonoscopy (0-0.02%)

Biliary/pancreatic stent without sphincterotomy (0.3%)

ERCP without sphincterotomy*

EUS without FNA

Gastric (7.2%)

Duodenal/ampullary

1-3 cm (4.5%)

>3 cm (10.3%)

Colonic (0.7-3.3%)

Endoscopic mucosal resection (22%)

Biliary sphincterotomy (2.0-3.2%)

Colonic (0.7-3.3%)

EUS without FNA

Flexible sphincterotomy + biopsy*

Endosonography without FNA

Wireless capsule endoscopy*

Pneumatic or bougie dilation (1.7%)

PEG placement (0.2-2.5%)

Endosonography-guided FNA (0.5-2.9%)

Laser ablation and coagulation (1.1%)

Treatment of varices (2.4-25.4%)

Becker et al. Am J Gastroenterol 2009; Kwok et al. Am J Gastroenterol 2009; Anderson et al. GIE 2009.

*Limited data, presumed negligible

Colonoscopy: Risk of GI BleedN=21,375 (CORI Database)

Variables

Complications directly related to

colonoscopy*OR (95% CI)

GI bleeding was the most common complication requiring hospitalization:

Incidence 1 6/1000 exams( )

60-69 years 1.2 (0.5-2.7)

70-79 years 2.1 (0.9-4.6)

>80 years 2.4 (0.8-7.2)

Polypectomywith cautery

6.7 (2.8-16.1)

>1 polypectomywith cautery

12.1 (5.1-28.7)

Incidence 1.6/1000 exams (1.1-2.2)

Transfusion required in 0.8/1000 exams (0.5-1.3)

Risk of polypectomy bleed 2-12x: Age

Any polypectomy with

Ko et al. Clin Gastroenterol Hepatol 2010.

with cautery

Pre-procedurewarfarin use

2.9 (1.2-7.0)

Pre-procedureclopidogrel use

Not statistically significant

*Includes perforation, GI bleeding, post-polypectomy syndrome, diverticulitis

Any polypectomy with cautery

Removal of >1 polyp

Pre-procedural warfarin

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Post-Polypectomy Bleeding With and Without Clopidogrel Therapy

Clopidogrel (n=142) No Clopidogrel (n=1243)

Single-site (VAMC), retrospective case-control

2

4

6

Per

cen

t (%

)

5.6%

3.0%2.1% 2.1%

3.5%

1.0%P=0 1 P=1 0

P=0.02

100% on ASA

Singh M et al. Gastrointest Endosc 2010.

0

P

Immediate(at endoscopy)

Delayed(< 4 weeks)

Post-Polypectomy Bleeding Type

P=0.1 P=1.0

Overall

Continuation of ASA After Endoscopic Control of Peptic Ulcer Bleeding

20.0%

Placebo (n=78)Low-dose ASA (n=78)

10.3% (3.4-17.2%) 9 0%

5 0%

10.0%

15.0%

ven

t R

ate

(%)

( )

5.4% (0.3-10.5%)

1.3% (0-3.8%)

9.0% (2.7-15.3%)

ARR 4.9%(NNT= 20)

ARI 7.7%(NNH= 13)

Sung et al. Ann Intern Med 2010.

0.0%

5.0%Ev

30-day Recurrent Bleeding

30-day All-Cause Mortality

( )(NNT 20)

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1.Avoid cessation of all antiplatelet therapies after PCI with stent placement when possible.

2. Avoid cessation of clopidogrel (even when ASA is continued) within the first 30 days of PCI and either DES or BMS placement

h ibl

Summary: Management of Antiplatelets

when possible.

3.Defer elective endoscopic procedures, possibly up to 12 months,if clinically acceptable from the time of PCI and DES placement.

4.

Perform endoscopic procedures, particularly those associated with high bleeding risk, 5-7 days after thienopyridine drug cessation. ASA should be continued when possible.

5.Resume thienopyridine and ASA drug therapy after the procedure once hemostasis is achieved.

6.Continue platelet-directed therapy in patients undergoing elective endoscopic procedures associated with low risk for bleeding.

Becker et al. Am J Gastroenterol 2009.

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Management of Antiplatelet Therapy

Becker et al. Am J Gastroenterol 2009; Anderson et al. Gastrointest Endosc 2009; Veitch et al. Gut 2008

Case 2

78-year-old female with history of: Stroke

Hyperlipidemia

Congestive heart failure (EF<40%)

Atrial fibrillation

PLAN: Pneumatic dilation of known h l iachalasia

How should you manage her anticoagulation?

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Low- vs. High-Risk Thromboembolic Conditions

Low-Risk High-RiskUncomplicated or

paroxysmal nonvalvular

f

Atrial fibrillation associated with:

Valvular heart disease

atrial fibrillation

Bioprosthetic valve

Mechanical valve in the

aortic position

Deep-vein thrombosis

Prosthetic valves

Active CHF

LVEF <35%

History of thromboembolic event

Hypertension

Diabetes mellitus

Age >75 yrs

Mechanical valve in any position and

previous thromboembolic event

Recently (<1 yr) placed coronary stent

Acute coronary syndrome

Non-stented PCI after MI

Anderson et al. Gastrointest Endosc 2009.

Endoscopy-Related GI Bleeding Risks

Low Risk (<1%) High Risk (>1%)

Diagnostic + biopsy

EGD (1 0% 0 1%)

Polypectomy

G t i (7 2%)

Bleeding risk varies with procedure type and presence/absence of therapeutic interventions.

EGD (1.0%-0.1%)

Double balloon enteroscopy(0.1%)

Colonoscopy (0-0.02%)

Biliary/pancreatic stent without sphincterotomy (0.3%)

ERCP without sphincterotomy*

EUS without FNA

Gastric (7.2%)

Duodenal/ampullary

1-3 cm (4.5%)

>3 cm (10.3%)

Colonic (0.7-3.3%)

Endoscopic mucosal resection (22%)

Biliary sphincterotomy (2.0-3.2%)P i b i dil i (1 %)EUS without FNA

Flexible sphincterotomy + biopsy*

Endosonography without FNA

Wireless capsule endoscopy*

Pneumatic or bougie dilation (1.7%)

PEG placement (0.2-2.5%)

Endosonography-guided FNA (0.5-2.9%)

Laser ablation and coagulation (1.1%)

Treatment of varices (2.4-25.4%)

Becker et al. Am J Gastroenterol 2009; Kwok et al. Am J Gastroenterol 2009; Anderson et al. GIE 2009.

*Limited data, presumed negligible

Pneumatic or bougie dilation (1.7%)

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Thromboembolic Risk: Atrial Fibrillation

3.0%

te (

%)

2.2% (0.8-6.3%)Absolute Risk

1 2 per 1000 patients Thromboembolic risk still 3.0% among high-

i k ti t

1.0%

2.0%

mb

oem

bo

lic R

at

0.4% (0.2-1.0%)

1-2 per 1000 patients

4-7 days

risk patients: Age >80 years

History of stroke

Hyperlipidemia

Hypertension

Family history of vascular disease

0.0%Th

ro

Anticoagulation (INR <1.3) Interruption Interval (days)

<5 days >7 days

Garcia et al. Arch Intern Med 2008; Eisen et al. Gastrointest Endosc 2002.

Family history of vascular diseaseBlacker et al. Neurology 2003.

Management of AnticoagulantsEfficacy and Safety of Bridge Therapy:

In patients requiring temporary interruption of warfarin therapy, bridge therapy is associated with low risk of thromboembolic and majorwith low risk of thromboembolic and major bleeding complications.

Evidence for bridge therapy with LMWH or UFH for endoscopic procedures is limited.

Douketis et al. Arch Intern Med 2004.

Anderson et al. Gastrointest Endosc 2009; Veitch et al. Gut 2008.

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Endoscopic Procedures in Acutely Bleeding Patients

Patient presenting with GI bleeding (GIB) in the setting of a supratherapeutic INR

Patient who presents with ACS and GIB

Patient who bleeds following anticoagulation for stent placement, ACS or neurological event

Acute GIB in Anticoagulated Patients: Case-Control Study

N=23 cases (severe GIB while taking warfarin); N=50 matched controls*

INR range 1.5-6.0; Corrected to 1.5-2.5 with FFP

Endoscopic therapy is effective even with elevated INRs

Warfarin(n=23)

No Warfarin(n=50)

Technical success 22 (95.6%) 47 (94.0%)

Injection:heater probe 18:4 36:11

Continued bleeding/rebleeding 4 (17.4%) 9 (18.0%)

Emergency surgery 2 (8.7%) 4 (8.0%)

Choudari & Palmer. Gut 1994.

g y g y ( ) ( )

Mean PRBCs transfused 6.0 (0.79) 4.48 (0.50)

Median duration of admission (d) 10 (4-57) 7 (3-84)

30-day mortality 0 2 (4.0%)

*Controls matched for age, gender, presence of shock on admission, and endoscopic findings

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Impact of Anticoagulation on RebleedingFollowing Endoscopic Therapy

N=233 patients with nonvariceal bleeding

INR at time of Adjusted OR*: 0.50 (0.21-1.16) endoscopy is not predictive of rebleeding

*Controlling for age, comorbidity, antiplatelet use, post-procedure heparin and PPI use,

hypotension, ulcer as bleeding source, and active bleeding at endoscopy

Normalizing INR d t

• N=103 INR >1.3 • Mean INR 1.8 (1.3-2.7)

• Rebleeding rate similar with and

Wolf A. Am J Gastroenterol 2007.

INR does not reduce

rebleeding but does delay endoscopy

• Rebleeding rate similar with and without reversal agent: 24.7% vs. 30.0% (p=0.54)• Significant delay in endoscopy with normalization of INR

• 20.9 h vs. 73.6 h (p<0.0001)

Endoscopic Procedures in Acutely Bleeding Patients

Patient presenting with GI bleeding (GIB) in the setting of a supratherapeutic INR

Patient who presents with ACS and GIB

Patient who bleeds following anticoagulation for stent placement, ACS or neurological event

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Utility of Endoscopy in Patient with Concomitant GIB and ACS

Retrospective, Durham VAMC medical record review (1/1996-12/2002)

N=183 patients EGD within days of initial ACS (n=105) or GIB (n=78)

• Urgent EGD should be performed in patients with GIB as the inciting event or those with ACS who experience hematemesis or hemodynamic instability

Hi h b bilit f fi di

• Performing EGD in ACS patients may still alter whether cardiac catheterization is performed during th h it li ti

4

6

8

10

OR

(95

% C

I)

3.9 (1.8-8.5)3.1 (1.3-7.6) 3.1 (1.4-6.9)

High probability of finding treatable lesion

the hospitalization Influenced timing of cardiac catheterization in 43%

Lin S. Dig Dis Sci 2006.

0

2

4

EG

D O

Inciting event: GIB (vs. ACS)

Hematemesis(vs. none)

Hemodynamic instability (vs. none)

Endoscopic Procedures in Acutely Bleeding Patients

Patient presenting with GI bleeding (GIB) in the setting of a supratherapeutic INR

Patient who presents with ACS and GIB

Patient who bleeds following anticoagulation for stent placement, ACS or neurological event

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Urgent Endoscopy in the Patient with ACS or Recently Placed Stent

1-3% develop GIB with ACS Mortality risk: 4-7 times more than non-bleeders*

High procedure-related mortality on the day of the ACS event 12%**

Mortality risk drops 1-2% within 30 days of ACS Mortality risk drops 1 2% within 30 days of ACS and diagnostic yield is high (85%)†

*Al-mallah AM et al. J Thromb Thrombolysis 2007; Abbas AE et al. Am J Cardiol 2005.**Spier BJ et al. J Clin Gastroenterol 2007.†Cappell MS. Am J Med 1999.

Anticoagulant Summary: Urgent Setting

Endoscopy therapy is very effective– even in patients with elevated INR

Rebleeding rates is unaffected by pre- Rebleeding rates is unaffected by pre-procedural INR Correcting INR delays time to procedure

Patients who present with GIB leading to ACS should be scoped High likelihood of finding an important lesion High likelihood of finding an important lesion

Peri-procedural risks are high in the first 24 hours of an ACS event, but decline to 1-2% by 30 days

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Antiplatelet Summary

To minimize risk: One size does not fit all.

B l i di ti d l i k f th b i Balance indication and real risk of thrombosis with short-term cessation, vs. indication and endoscopic bleeding risk

Consult with cardiologist/hematologist

Discuss recommendations with your patient