Early And Long Term Treatment With Clopidogrel In Coronary ...

Early And Long Term Treatment With Clopidogrel In Coronary

Artery Disease

פרופ’ יוסף רוזנמןמכון הלב, בי"ח

וולפסון2005דצמבר

Acute Coronary Syndromes

Acute Coronary Syndrome

No ST Elevation ST Elevation

Unstable Angina Myocardial InfarctionNon Q MI Q wave MI

Non ST Elevation MI

Braunwald E et al. J Am Coll Cardiol 2000;36:970–1062.

Initial Treatment Strategy

ACS

ST Elevation Non ST Elevation

1. Anti-thrombotic Rx (+ Fibrinolysis)

2. Early / Primary PCI

1. Anti-thrombotic Rx

2. Early PCI

Reperfusion and culprit plaque stabilization

The best way to stabilize a culprit plaque is with a stent

Culprit plaque stabilization

Minimize peri-procedural complications (related to the treated plaque)

Thrombosis etc

Stabilize the rest of the non-occlusive narrowings

Prevent progressionPrevent atherothrombosis

1

2

Goals of Peri – PCI Medical Treatment (short and long term)

The Clinical QuestionsCombination Rx. (ASA + Clopidogrel)

When angiography / PCI is planned in a patient already treated with ASA:Is additional pre-treatment with clopidogrel improving outcome (until angiography / PCI, at 1 month – or longer)Is continuation of clopidogrel beyond 1 month improving long-term outcome

1

2

Goals of therapy1. Prevent ischemic events until coronary

angiography / PCI Before plaque stabilization was achieved

2. Prevent PCI / stent related ischemic complications

Clopidogrel before coronary angiography - Patients with ACS 1

Clopidogrel before coronary angiography - Patients with ACS

• ST Elevation–CLARITY

• Non ST Elevation–CURE

1



1Clopidogrel before coronary

angiography - Patients with ACS

Study Design

Fibrinolytic, ASA, Heparin

Clopidogrel300 mg + 75 mg qd

Coronary Angiogram(2-8 days)

Primary endpoint:Occludedartery (TIMI Flow Grade 0/1)or D/MI by timeof angio

randomize

Placebo

Double-blind, randomized, placebo-controlled trial in3491 patients, age 18-75 yrs with STEMI < 12 hours

StudyDrug

30-day clinical follow-up

Open-labelclopidogrelper MD in

both groups

Primary Endpoint:Primary Endpoint:Occluded Artery Occluded Artery (or D/MI by time of angio)(or D/MI by time of angio)

15.0

21.7

0

5

10

15

20

25

Oc

clu

de

d A

rte

ry o

r D

ea

th/M

I (%

)

PlaceboPlaceboClopidogrelClopidogrel

P=0.00000036P=0.00000036P=0.00000036P=0.00000036

Odds Ratio 0.64Odds Ratio 0.64(95% CI 0.53-0.76)(95% CI 0.53-0.76)


1.00.4 0.6 0.8 1.2 1.6

ClopidogrelClopidogrelbetterbetter

PlaceboPlacebobetterbetter

n=1752 n=1739

36%Odds Reduction

36%Odds Reduction

15.4

18.6 19.5

23.3

29.3

33.0

0

5

10

15

20

25

30

35

(%)

Clopidogrel

Placebo

Need for Urgent orAdditional Treatment

21% P=0.01

21% P=0.005

16% P=0.07

Early Angio(w/in 48 hrs)

Urgent Revasc(index hosp)

GP IIb/IIIaif PCI

CV Death, MI, RI CV Death, MI, RI Urg Revasc Urg Revasc

days

Per

cen

tag

e w

ith

en

dp

oin

t (%

)P

erce

nta

ge

wit

h e

nd

po

int

(%)

05

1015

0 5 10 15 20 25 30

PlaceboPlacebo

ClopidogrelClopidogrel


P=0.026P=0.026

20%20%20%20%

1

CLARITY: Patient Management

Clopidogrel Placebo

Parameter (n=1,752) (n=1,739)

Symptom onset to fibrinolytic (hours) 2.7 2.6

Fibrinolytic to study drug (minutes) 10 10

Median doses of study medication 4 4

Angiography performed (%) 94 94

Study drug to angiography (hours) 84 84

Coronary revascularization (%): 63 63

PCI 57.2 56.6

CABG 5.9 6.0

Sabatine M et al. New Engl J Med 2005; 352: 1179–1189.

PCI-CLARITY: MI, Stroke, or CV DeathEvents pre and post PCI

***MI or Stroke

Pat

ien

ts w

ith

en

dp

oin

t (%

)

0

5

10

15

7.5

12.0 Clopidogrel Pretreatment (n=933)

No Pretreatment (n=930)

41%p=0.001

OverallEvents*

Pre-PCIEvents**

4.0

6.2

38%p=0.03

3.6

6.2

46%p=0.008

Post-PCIEvents*

M Sabatine, et al. JAMA 2005,

Prehospital Fibrinolysis with Double Antiplatelet Therapy in Acute ST-Elevation Myocardial Infarction:

The Clarity Ambulance SubstudyThe Clarity Ambulance Substudy

Prehospital Fibrinolysis with Double Antiplatelet Therapy in Acute ST-Elevation Myocardial Infarction:

The Clarity Ambulance SubstudyThe Clarity Ambulance Substudy

Montalescot G. ESC, September 2005

Substudy Sites and Patient Numbers

France: 172 patientsL Soulat: 57Y Lambert: 48F Lapostolle: 28F Thieuleux: 21C Gully: 10D Pollet: 5D Galley: 2L Olliver: 1

UK: 40 patientsJ Adgey: 27J Purvis: 13

Sweden: 5 patientsJ-E Karlsson: 5

217 patients in total


Angiographic & ECG Parameters: Ambulance vs. Non-Ambulance

TFG 3 64.4 64.4 NS

Complete* ST resolution at ECG

90 min

180 min

47.2

63.2

37.0

52.7

0.02

0.05

*Complete considered to be >70%; ECG=electrocardiogram

p value

Event rate (%)

Ambulance Non-ambulance

Non-ambulance betterAmbulance better

Odds ratio (95% CI)

0.50 1.0 1.5 2.0 2.5 3.0


0 0.5 1.0 1.5 2.0

Ambulance

Non-ambulance

Overall

Clopidogrel better Placebo better

Odds ratio (95% CI)

Primary Endpoint of TIMI Flow Grade 0/1, MI or Death

0.60 (0.301.17)

0.64 (0.530.76)

0.65 (0.540.77)



1Clopidogrel before coronary

angiography - Patients with ACS

Clopidogrel 75mg q.d. + ASA 75-325 mg q.d.*

(6259 patients)

Placebo + ASA 75-325 mg q.d.*(6303 patients)

Day

1

6 m

. Vis

it

9 m

. Vis

it

12 m

.

or F

inal

Vis

it

3 m

. Vis

it

Dis

char

ge V

isit

1 m

. Vis

it

Patients withAcute Coronary

Syndrome

(unstable angina or non-ST-segment

elevation MI)

RR

Plac

ebo

load

ing

dose

R = Randomization* In combination with other standard therapy The CURE Trial InvestigatorsThe CURE Trial Investigators. N Engl J Med. 2001;345:494-502.

Study DesignStudy DesignStudy DesignStudy Design

3 months double-blind treatment 12 months3 months double-blind treatment 12 months

Clopidogrel 300 mg loading dose

CURE

0.00

0.02

0.04

0.06

0.08

0.10

0.12

0.14

Cu

mu

lati

ve

Ha

zard

Ra

te

Clopidogrel Clopidogrel + ASA*+ ASA*

33 66 99

Placebo Placebo + ASA*+ ASA*

Months of Follow-UpMonths of Follow-Up

11.4%11.4%

9.3%9.3%

20% RRR20% RRRPP < 0.001 < 0.001

N = 12,562N = 12,562

00 1212

* In combination with standard therapy

The CURE Trial InvestigatorsThe CURE Trial Investigators. N Engl J Med. 2001;345:494-502.

Primary End Point - MI/Stroke/CV DeathPrimary End Point - MI/Stroke/CV DeathPrimary End Point - MI/Stroke/CV DeathPrimary End Point - MI/Stroke/CV DeathCURE

0.00

0.01

0.02

0.03

0.04

0.05

0.06

Cu

mu

lati

ve

Ha

zard

Ra

te

Clopidogrel Clopidogrel + ASA*+ ASA*

1010 2020 3030

Placebo Placebo + ASA*+ ASA*

Days of Follow-UpDays of Follow-Up

00

21% RRR21% RRRPP = 0.003 = 0.003

N = 12,562N = 12,562

* In combination with standard therapy


MI/Stroke/CV Death within 30 DaysMI/Stroke/CV Death within 30 DaysMI/Stroke/CV Death within 30 DaysMI/Stroke/CV Death within 30 Days

CURE

1

2.1%

1.5%

0

0.5

1

1.5

2

2.5

Placebo + aspirin Clopidogrel + aspirin

CV

dea

th,

no

nfa

tal

MI,

stro

ke o

r re

frac

tory

or

seve

re i

sch

emia

34%

NEJM 2001; 345:495-502

MI/Stroke/CV Death or severe Ischemia at 24 hours

CURE

1

2%

1.1%

0

0.5

1

1.5

2

2.5

Placebo +aspirin

Clopidogrel +aspirin

% p

atie

nts

req

uir

ing

thro

mb

oly

tic

ther

apy

43%7.2%

5.9%

012345678

Placebo +aspirin

Clopidogrel +aspirin

% p

atie

nts

req

uir

ing

GP

IIb

/III

a in

hib

ito

rs

18%

NEJM 2001; 345:495-502

Need for Additional Anti-Thrombotic After Randomization

P< 0.0010.001 P= 0.0030.003

Thrombolysis GP IIb/IIIa Inhibitor

CURE

1

Should clopidogrel be added GP IIb/IIIa Should clopidogrel be added GP IIb/IIIa antagonists as pretreatment before antagonists as pretreatment before coronary angiography (“upstream”) ?coronary angiography (“upstream”) ?

Should clopidogrel be added GP IIb/IIIa Should clopidogrel be added GP IIb/IIIa antagonists as pretreatment before antagonists as pretreatment before coronary angiography (“upstream”) ?coronary angiography (“upstream”) ?

Is there additional benefit to clopidogrel that would justify:

Increased CABG bleeding

or alternatively

Need to postpone CABG for 3-5 days

No data in the literature however

Adhesion

The Role of Platelets in Atherothrombosis

Aggregation3

Reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

1

Activation2

Conclusions: Early Clopidogrel TherapyConclusions: Early Clopidogrel TherapyConclusions: Early Clopidogrel TherapyConclusions: Early Clopidogrel Therapy

Treatment with clopidogrel is indicated as soon as possible in patients with acute coronary syndrome

ST elevation and non ST elevation

Treatment is effective to reduce ischemic complications

Before coronay angiography

During and after PCI

1

Conclusions: Early Clopidogrel TherapyConclusions: Early Clopidogrel TherapyConclusions: Early Clopidogrel TherapyConclusions: Early Clopidogrel Therapy

Loading dose should be 600mg to achieve early optimal antiplatelet effect

?? 300mg in patients after fibrinolytic therapy

It is unclear whether therapy should be added to “upstream” GP IIb/IIIa antagonists

Especially in high risk patients in whom the likelihood for CABG is high

1

Minimize peri-procedural complications (related to the treated plaque)

Thrombosis etc

Stabilize the rest of the non-occlusive narrowings

Prevent progressionPrevent atherothrombosis

1

2

Goals of Peri – PCI Medical Treatment (short and long term)

The Clinical QuestionsCombination Rx. (ASA + Clopidogrel)

When PCI is planned in a patient already treated with ASA:Is additional pre-treatment with clopidogrel improving outcome (until PCI, at 1 month – or longer)

Is continuation of clopidogrel beyond 1 month after PCI / stent improving long-term outcome

1

2

Discharge/Post-Discharge Discharge/Post-Discharge Medications - GuidelinesMedications - Guidelines

ASA, if not contraindicatedASA, if not contraindicated

Clopidogrel, when ASA contraindicatedClopidogrel, when ASA contraindicated

Aspirin + Clopidogrel for up to 9 monthsAspirin + Clopidogrel for up to 9 months

-blocker, if not contraindicated-blocker, if not contraindicated

Lipid Lipid agents + diet, if LDL >130 mg/dL agents + diet, if LDL >130 mg/dL

ACE Inhibitor: CHF, EF < 40%, DM, or HTNACE Inhibitor: CHF, EF < 40%, DM, or HTN

ASA, if not contraindicatedASA, if not contraindicated

Clopidogrel, when ASA contraindicatedClopidogrel, when ASA contraindicated

Aspirin + Clopidogrel for up to 9 monthsAspirin + Clopidogrel for up to 9 months

-blocker, if not contraindicated-blocker, if not contraindicated

Lipid Lipid agents + diet, if LDL >130 mg/dL agents + diet, if LDL >130 mg/dL

ACE Inhibitor: CHF, EF < 40%, DM, or HTNACE Inhibitor: CHF, EF < 40%, DM, or HTN

II IIaIIa IIbIIb IIIIII

2

PCI

PLACEBO + ASA *

CLOPIDOGREL+ ASA *

30 days post PCIEnd of follow-upUp to 12 months

after randomization

Open-label thienopyridineOpen-label thienopyridine

PretreatmentOpen-label thienopyridineOpen-label thienopyridine

PretreatmentN = 2,658 patients undergoing PCI

N = 1345

N = 1313

PCI-CURE

Overall Study Design: PCI-CURE

R

Mehta, SR. et al for the CURE Trial Investigators CURE Trial Investigators. N Engl J Med. 2001;345:494-502.

PCI-CURE

Question 1Question 1


Clo

pid

og

rel

Clo

pid

og

rel

Arm

Arm

Pla

ceb

o

Pla

ceb

o

Arm

Arm

PCI*PCI* 28 Days28 Days

Placebo + Placebo + ASAASA†† (325 mg) (325 mg)

Randomization -Randomization -Pre-treatmentPre-treatment

Clopidogrel 300 mgClopidogrel 300 mg+ ASA+ ASA†† (325 mg) (325 mg)

Clopidogrel 75 mg QDClopidogrel 75 mg QD+ ASA+ ASA†† 325 mg QD 325 mg QD

Clopidogrel 75 mg QDClopidogrel 75 mg QD+ ASA+ ASA†† 325 mg QD 325 mg QD

RR

12 Months12 Months

Steinhubl S, Berger P, Tift Mann III J et al. Steinhubl S, Berger P, Tift Mann III J et al. JAMAJAMA. 2002;Vol 288,No 19:2411-2420.. 2002;Vol 288,No 19:2411-2420.

Placebo QDPlacebo QD+ ASA+ ASA†† (81-325 mg) QD (81-325 mg) QD

Clopidogrel 75 mg QDClopidogrel 75 mg QD+ ASA+ ASA†† (81-325 mg) QD (81-325 mg) QD

Overall Study Design: CREDO

Question 1Question 1 Question 2Question 2

1 2

Open labelclopidogrel

continuationcontinuation

Methodological Pitfall

Can a study with a single randomization provide an answer to two questions?

Alternatively

Should a second randomization be done in order to answer the second question?

PCI

PLACEBO + ASA *

CLOPIDOGREL+ ASA *

30 days post PCIEnd of follow-upUp to 12 months

after randomization



Pretreatment

N = 1345

N = 1313

PCI-CURE

Study Designsingle randomization

R

Mehta, SR. et al for the CURE Trial Investigators CURE Trial Investigators. N Engl J Med. 2001;345:494-502.

PCI-CURE

Continuation

Continuation

PCI

PLACEBO + ASA *

CLOPIDOGREL+ ASA *



Pretreatment

N = 1345

N = 1313

PCI-CURE

Alternative Study Designtwo randomizations

R1

Mehta, SR. et al for the CURECURE Trial Investigators Trial Investigators. N Engl J Med. 2001;345:494-502.

PCI-CURE

R2

R2

Clop.

Placebo

Continuation

Continuation


Is it just methodology?

Can we really expect long term benefit from early antiplatelet therapy?

Adjunct antiplatelet therapy for PCI

EPISTENT– Randomized study designed to determine the effect of

treatment with abciximab TARGET

– Randomized study designed to show that tirofiban is not inferior to abciximab

– Post-hoc nonrandomized comparison among those who were or were not pre-treated with clopidogrel

PCI-CURE– Subgroup of CURE patients who underwent PCI– Randomized comparison of pre-treatment and continued

clopidogrel therapy vs. placebo

4.8

3.9

3

0.91.3

0.8

0

5

1 month 1 month to 1 year

EPISTENT

TARGET

PCI-CURE

Absolute reduction of Death or MI at 1 month and 1 year

-Abciximab-Early clopidogrel-Early and continued clopidogrel

% r

edu

ctio

n

*

* 6 month data in TARGET

Early and long term reduction of death or MI from antiplatelet therapy in patients with ACS

Long Term Clopidogrel Post PCI

Clinical guidelines: 9 months to 1 year in patients with ACS

However, current data does not fully support this recommendation

What should we do?

2

Comulative event rate in primary prevention stable CAD and ACS

ACS

Stable

Primary

Risk of vascular event after ACSR

isk

of e

vent

Time after ACS

Stable CAD

Commulative risk

Risk per time

Risk of vascular event after ACShigh and low risk

Ris

k of

eve

nt

Time after ACS

High risk

Low risk

Risk of bleeding after initiation of clopidogrel (high and low risk)

Ris

k of

eve

nt

Time after clopidogrel

High risk

Low risk

Fixed, except for the initial few days heparin, catheterization

Risk of event (vascular/bleeding) after ACS and clopidogrel

Ris

k of

eve

nt

Time after ACS3 months ??

vascular

bleeding


Ris

k of

eve

nt


vascular

bleeding

> 1 year

High vascular risk


Ris

k of

eve

nt


vascular

bleeding

< 1 months

High bleeding riske.g. coumadin


Ris

k of

eve

nt


Long term clopidogrel for patients withHigh risk for vascular eventLow bleeding risk

Short term clopidogrel for patients withLow risk for vascular eventHigh bleeding risk

vascular

bleeding

Who is ”High Risk”Patients in whom long term clopidogrel should be considered

The vulnerable patientTIMI risk scoreAspirin FailureOthers



ACS PathophysiologyInflammation, Plaque Rupture, Thrombosis, and MicroembolizationInflammation, Plaque Rupture, Thrombosis, and Microembolization

Quiescent plaqueQuiescent plaque

Plaque formationLipids, other risk factors

InflammationLDL, others, Infection?

Plaque rupture (erosion)? Macrophages, metalloproteinases

ThrombosisPlatelet Activation, Thrombin

Plaque formationLipids, other risk factors

InflammationLDL, others, Infection?

Plaque rupture (erosion)? Macrophages, metalloproteinases

ThrombosisPlatelet Activation, Thrombin

Vulnerable plaqueVulnerable plaque

MacrophagesFoam Cells

Collagen platelet activation

TF TF ClottingClotting Cascade Cascade

Lipid coreLipid core

Metalloproteinases

InflammationInflammation

Courtesy of David Kandzari.

PlaquePlaque rupturerupture

Culprit plaqueCulprit plaque

Platelet-thrombin micro-emboliPlatelet-thrombin micro-emboli

Atherosclerotic Plaques -Terminology

• Culprit– Responsible for the clinical event

• Vulnerable– High risk to become culprit (cause

clinical event)

• QuiescentQuiescent (Stable)– Primary or healed (vulnerable or culprit)

Fuster, V. et al. J Am Coll Cardiol 2005;46:937-954

Coronary Artery Disease: Diffuse disease with a variable mix of stable, vulnerable and culprit plaques

Culprit and healed plaques in a coronary bifurcation

N Engl J Med 2000;343:915-22

Angiograms of 253 patients with acute MIComplex Plaques:

Single: 153 - 60.5%Multiple: 100 – 39.5%

Clinical Outcome at 1 Year –Single vs. Multiple Complex Plaques

Similar results when analysis was restricted to patients with multivessel coronary disease:74.5% of single91.0% of multiple

Characteristics of Carotid Plaques: Patients with Unstable versus Stable Angina

Multivariate analysis: UA and CRP >3 mg/l were independently and strongly associated with complex carotid plaques

Vulnerable Patient – at high risk for vascular event

coronary elsewhere

Who is the vulnerable patient?

Patient with current multiple complex plaques– Coronary, carotid etc

Patient with multiple uncontrolled risk factors– At risk to develop new complex plaques

Vulnerability cutoff value ?



TIMI Risk Score and Outcome

Budaj et al. circulation 2002

Excess major bleeding risk with clopidogrel is independent of the TIMI risk – it is 1%

TIMI Risk Score and Absolute Reduction of death/MI/Stroke with Clopidogrel

0.1

2.1 1.91.3

4.2

7.1

0

2

4

6

8

0-1 2 3 4 5 > 5

TIMI Risk Score

N= 752 2524 3730 3567 1593 396

Per

cen

t re

du

ctio

n

Major bleeding – 1%

Majority of patients



Aspirin Failure – Patient with acute vascular event (coronary, cerebral)

while being treated with aspirin

Aspirin was not enough to prevent the eventAspirin is ineffective as an antiplatelet

agent – resistance?Aspirin is effective as an antiplatelet agent

but the disease risk is high and there is a need for more aggressive antiplatelet therapy

Aspirin Resistance

Cellular FactorsInsufficient suppression

of COX-1

Overexpression of COX-2 mRNA

Erythrocyte-induced platelet activation

Increased norepinephrine

Generation of 8-iso-PGF2

Adapted with permission from Bhatt DL. J Am Coll Cardiol. 2004;43:1127-1129.

Aspirin Resistance

Genetic Polymorphisms

COX-1

GP IIIa receptor

Collagen receptor

vWF receptor

Clinical Factors Failure to prescribe

Noncompliance

Nonabsorption

Interaction with ibuprofen

Can be intermittent

Unfortunately (surprisingly) there is no subgroup analysis

of CAPRIE or CURE for patients who were on prior aspirin

However

There are other subgroup analyses

10

1234

9

5678

00 6 12 18 24 30 36

9.7%

8.1%

Aspirin

Clopidogrelp = 0.03

Months of Follow-up

43%

50

15

5

10

20

25

45

30

35

40

00 6 12 18 24 30 36

Aspirin

Clopidogrel

46.1%

p = 0.001

36.7%

Months of Follow-up

31%

Clopidogrel in patients with prior CABG CAPRIE substudy (N=1480)

Vascular deathCombined endpoint: Vascular death, MI, stroke or hospitalization for ischemia or bleeding

Circulation 2001; 103: 363-368

Ringleb, P. A. et al. Stroke 2004;35:528-532

Clopidogrel in patients with history of prior ischemic event - CAPRIE substudy (N=4496)

Overall 12562 9.3 11.4

Associated MI 3283 11.3 13.7No associated MI 9279 8.6 10.6

Male sex 7726 9.1 11.9Female sex 4836 9.5 10.7

65 yr old 6354 5.4 7.665 yr old 6208 13.3 15.3

ST-segment deviation 6275 11.5 14.3No ST-segment deviation 6287 7.0 8.6

Enzymes elevated at entry 3176 10.7 13.0Enzymes not elevated at entry 9386 8.8 10.9

Diabetes 2840 14.2 16.7No diabetes 9722 7.9 9.9

Low risk 4187 5.1 6.7Intermediate risk 4185 6.5 9.4High risk 4184 16.3 18.0

History of revascularization 2246 8.4 14.4No history of revascularization 10316 9.5 10.7

Revascularization after randomization 4577 11.5 13.9No revascularization after randomization 7985 8.1 10.0

Placebo + ASA*Characteristic

No. ofPatients

Clopidogrel + ASA*

Percentage of Patients with Event

Placebo BetterClopidogrel Better

Relative Risk (95% CI)

1.21.00.80.60.4* In combination with standard therapy


Beneficial Outcomes with Clopidogrel in Various SubgroupsBeneficial Outcomes with Clopidogrel in Various SubgroupsBeneficial Outcomes with Clopidogrel in Various SubgroupsBeneficial Outcomes with Clopidogrel in Various Subgroups

CURE

8.4

14.4

9.5

10.7

5

10

15

Yes No

Clopidogrel

Placebo

6.0% 1.2%

CURE: Impact of History of Revascularization

Percent of Patients with an Event

History of Revascularization

(N=2246) (N=10316)

Conclusions – early treatment

Clopidogrel loading should be given to patients with ACS (both STE and Non-STE) as soon as possible regardless* of the timing of the planned coronary angiography– * It is still unclear whether treatment can be

postponed when “upstream” GP IIb/IIIa is being used (especially when the likelihood of CABG is high).

• will be clarified by ongoing trial – “early ACS”

Clinical guidelines recommend 9-12 months clopidogrel to all patients with non-STE ACS

Treatment should be definitely continued as long as there is a risk for stent thrombosis– Longer duration

• high risk subset (multiple complex plaques, TIMI risk score >5, continuously elevated CRP?)

• Aspirin failure ?

– Shorter duration• High bleeding risk (e.g. coumadin etc)

Conclusions – long term treatment

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