Up-to-date : Antiplatelet Therapy for Acute Coronary Syndrome

1
Up-to-date Antiplatelet Therapy for Acute
Coronary Syndrome
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Acute Coronary Syndrome and ER Management
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Increasing CV Mortality
Bureau of Health Policy and Plan and Division of
Epidemiology, MOPH
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Top Ten Causes of Death in Thailand
Per 100,000 population
Bureau of Health Policy and Plan and Division of
Epidemiology, MOPH
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CAD 2 Major Presentations

• Stable angina
• Unstable angina / ACS

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Case 1 ?????????? (stable angina)

• Age 55
• Sex Male
• Past History HTN
• Occupation High stress
• Complaint
• Chest pain when he runs about 500 meters.
• Relieved with rest in 3 minutes.
• Occasional chest pain with stress

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Stable Angina Predictable Disease
????? ?????? ???
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• Age 50
• Sex Male
• Habit non-smoker
• Past History -
• Complaint
• Sudden onset of chest pain while resting
• No improvement after 15minutes

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What causes unstable symptom?
?
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Acute Coronary Syndrome
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Plaque Rupture
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Active Platelet
Scanning electron micrograph of dormant platelets
Activated, aggregating platelets with fibrin
strands
Lip GYH et al. Circulation 1996 94 425-431.
Lip GYH et al. Am Heart J 1996 131 724-730.
15
?????????
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Truths about Plaque Rupture

• No warning.
• Can occur after normal EST.
• No precipitating cause ??BP, ?activitiy

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Spectrum of ACS
Accelerating/ New onset Angina
Unstable Angina, EKG-, Trop-
UA with Trop / NSTEMI / NQWMI
STEMI / QWMI
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Non ST Elevation MI
ST Elevation MI
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Difference in Mortality
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??????????????????? ACS

• Prevent plaque rupture
• Statins
• Decrease O2 need
• Decrease platelet activation and aggregation
• Open blocked vessel

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????????????? ACS (NSTEMI and STEMI)

• ????????????????
• B-blockers (? mode of administration)
• Ca blockers as alternatives
• Nitrates
• O2
• Morphine
• Anti-coagulation
• ACEI

Class I Recommendation
If no contra-indications!
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Aspirin

• Mechanism of action
• Irreversible COX inhibitor
• Prevents thromboxane A2 formation
• Diminishing platelet aggregation
• Indication Class IA
• Dosage 160-300mg

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Efficacy of ASA Reduction of Death or MI in
Unstable Angina
0.25
Placebo
0.20
Risk ratio after 1 year 0.5295 Cl 0.370.72
(p0.0001)
0.15
Probability of death or MI
0.10
ASA 75 mg
0.05
0.00
0
3
6
9
12
Months
Wallentin LC et al JACC 19911815871593
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Lytics ASA in STEMI ISIS-2
42 p lt0.00001
23 p lt0.00001
25 p lt0.00001
13.2
14
12.0
11.8
12
9.4
9.2
10
8.0
8
5-week mortality ()
6
4
2
0
Placebo versus streptokinase
Placebo versus ASA 162 mg
Neither versus both
Odds reduction
1. ISIS-2 Collaborative Group. Lancet 1988 2
349?360.
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Antiplatelet and Cardiovascular Events
Category of trial Prior MI Acute MI Prior
stroke/TIA Other high risk All high risk (all the
above) All low risk (primary prevention) All
trials
MI/Stroke or Vascular Death Anti-platelet
adjusted controls 13.5
17.1 10.6 14.4
18.4 22.2 6.9
9.2 4,183/36 536 5,400/36
711 (11.4) (14.7)
652/14,608 708/14,604 (4.46)
(4.85) 4 835/51,144
6,108/51,315 (9.5)
(11.19)
OR (SD)
No.of trials
ORCI
11 9 18 104 142 3 145
25(4) 29(4) 22(4) 32(4) 27(2) 10(6) 25(2)
0 0.5 1.0 1.5
2.0
better worse
2p lt0.00001
Antiplatelet Trialist Collaboration BMJ. 1994
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ADP Antagonist

• Thienopyridine derivative
• Mechanism of action
• ADP receptor antagonist

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Mode of Action
COX, cyclooxygenase ADP, adenosine diphosphate
TxA2, thromboxane A2
Schafer AI Am J Med 1996101199209
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• PLAVIX is a selective and potent inhibitor of
  platelet aggregation
• PLAVIX binds to a receptor and blocks ADP-induced
  aggregation
• Blocking ADP binding results in a coupled
  biochemical reaction that inhibits binding of
  fibrinogen to the GPIIb/IIIa receptor on the
  platelet surface
• The end result is an irreversible modification of
  the platelet, rendering it unable to aggregate

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Clopidogrel in Atherosclerotic Disease (CAPRIE)

• Patient population
• Recent ischemic stroke
• Recent MI
• Symptomatic peripheral arterial disease
• ASA 325mg vs Clopidogrel 75mg
• Follow-up 1 to 3 years

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Clopidogrel in Unstable Angina to Prevent
Recurrent Events CURE Design
N ?12 500 28 countries
Clopidogrel 300 mg loading dose
Clopidogrel75 mg o.d.(6250 patients)
ASA 75325 mg
ACS without ST elevation
R
R
Double-blind treatment 3 to 12 months
Double-blind treatment 3 to 12 months

• Presented within 24hrs
• Clinical symptoms
• Ischemic EKG change

ASA 75325 mg
Placebo 1 tab o.d.(6250 patients)
12 monthor final visit
6 month visit
3 month visit
1 month visit
9 month visit
Day 1
Discharge visit
Placebo loading dose
CURE Study Investigators Eur Heart J
20002120332041
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CURE Primary Endpoint
of patients with recurrent ischemic event
(cardiovascular death, MI, or stroke)
14
11.4
Benefits were seen within hours and continued to
increase over the 12 months
12
9.3
10
20 RRR p0.00009 n12,562
8
6
4
Standard therapy Clopidogrel standard therapy
2
0
0
1
2
3
4
5
6
7
8
9
10
11
12
Months of follow-up
including ASA
The CURE Investigators. N Eng J Med August 2001
34
Primary Outcome Subgroups
events
2N
Standard therapy
Clopidogrel Standard therapy
RR (95 CI)
Patient characteristics
Overall 12 562 11.4 9.3 ST deviation
6275 14.3 11.5 ST deviation - 6287 8.6 7.0 Entr
y enzymes elevated 3176 13.0 10.9 Entry enzymes
elevated - 9386 10.9 8.8 Diabetes
2840 16.7 14.2 Diabetes - 9722 9.9 7.9 Risk Low
4187 6.7 5.1 Intermediate 4185 9.4 6.5 High 418
4 18.0 16.3 Rev after randomization
4577 13.9 11.5 Rev after randomization
- 7985 10.0 8.1 History of rev
2246 14.4 8.4 History of rev - 10 316 10.7 9.5
with condition - without condition
Rev, revascularization
0.4
0.6
0.8
1.0
1.2
including ASA
The CURE Investigators. N Eng J Med August 2001
35
PCI-CURE
CV death, MI or urgent TVR at 30d post PCI

• 30 risk reduction
• Absolute reduction 1.9
• P0.03

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PCI-CURE Long-term Efficacy
Composite of CV-death or MI from randomization to
end of follow-up
12.6
Placebo Clopidogrel
0.15
31 RRR p0.002 n2658
8.8
Cumulative hazard rates
0.10
0.05
0.0
0
100
200
300
400
10
40
Days of follow-up
a
b
a median time from randomization to PCI (10
days) b 30 days after median time of PCI up to
12 months on top of standard therapy
including ASA
The CURE Investigators. Lancet August 2001
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CURE Major Bleeding by ASA Dose
Peters RJ et al. Circulation 20031081682
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2002 ACC/AHA UA/NSTEMI Guidelines Update

• Class I
• ASA should be administered as soon as possible
  after presentation and continued indefinitely
  (IA)
• Clopidogrel 75 mg daily (in the absence of
  contraindications) when ASA is not tolerated (IA)
• If early non-interventional approach is planned,
  clopidogrel should be added to ASA as soon as
  possible on admission and administered for at
  least 1 month (IA) and for up to 9 months (IB)
• If PCI planned, clopidogrel should be started and
  continued for at least 1 month (IA) and up to 9
  months in patients who are not at high risk for
  bleeding (IB)

1. Braunwald E et al.
FOR INTERNAL USE ONLY
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2002 ACC/AHA UA/NSTEMI Guidelines Update

• Class I
• In patients taking clopidogrel in whom elective
  CABG is planned, the drug should be withheld for
  5?7 days (IB)
• Anticoagulation with subcutaneous low molecular
  weight heparin (LMWH) or intravenous (iv)
  unfractionated heparin (UFH) should be added to
  antiplatelet therapy with ASA and/or clopidogrel
  (IA)
• A platelet GPIIb/IIIa antagonist should be
  administered, in addition to ASA and heparin, to
  patients in whom catheterization and PCI are
  planned. The GPIIb/IIIa antagonist may also be
  administered just prior to PCI (IA)

Also known as non-Q-wave MI
1. Braunwald E et al.
FOR INTERNAL USE ONLY
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2002 ACC/AHA UA/NSTEMI Guidelines Update

• Class I
• For long-term medical therapy, the combination of
  ASA and clopidogrel is recommended for 9 months
  after UA/NSTEMI (B)

Also known as non-Q-wave MI
1. Braunwald E et al.
FOR INTERNAL USE ONLY
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ALBION Assessment of best Loading dose of
clopidogrel to Blunt platelet activation,
Inflammation and Ongoing Necrosis

• 103 patients aged 18 to 85 years
• UA NSTEMI within the 48 hours prior to
  randomisation.
• 300mg, 600mg and 900mg
• Blood monitored every hour during the first 6
  hours then at 24 hours to determine the kinetics
  of inhibition of platelet aggregation.
• Within the first 24 hours, higher loading doses
  of clopidogrel induced faster onset of action and
  higher levels of inhibition of platelet
  aggregation than the indicated loading dose of
  300mg, in patients with ACS
• Similar safety profile among different dosage
  groups.

EuroPCR Congress in Paris on May 24
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Faster Onset of Action and Higher Level of
Platelet Inhibition
? plt 0.05 vs. 300 mg LD
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Faster Onset of Action and Higher Level of
Platelet Inhibition
? plt 0.05 vs. 300 mg LD
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Major Adverse Cardiac Events
300 mg n 35 600 mg n 34 900 mg n 34
Death (n) Non-fatal MI(n) Unplanned PCI (n) Hospitalization for recurrent angina (n) 0 1 1 2 0 2 0 0 0 0 0 0
TOTAL n () 4 (11.4) 2 (5.9) 0
New Q wave or CK gt 3 times the ULN
46
Safety
300 mg n 35 600 mg n 34 900 mg n 34
Bleeding Day 1- Discharge (n) Severe Moderate Mild TOTAL 0 1 10 11 0 0 10 10 0 1 13 14


GUSTO Classification
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Summary

• In patients with NSTEMI, 600 and 900 mg LDs
  compared to 300-mg LD provided
• More rapid and higher levels of IPA during the
  first 24 h
• Potential favorable trends on ischemic events and
  troponin release
• Greater reductions in some markers of platelet
  activation (PAC-1 and VASP) during the first 24
  hours
• Comparable safety profiles

IPA Inhibition of Platelet Aggregation
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Study Design
Double-blind, randomized, placebo-controlled
trial inpatients aged 18?75 years with STEMI 12
hours
Clopidogrel 300 mg loading dose / 75 mg QD
n1752
Thrombolysis, heparin and ASA
Study treatment until angiography (2?8 days) or
hospital discharge (maximum 8 days)
Clinical Follow-up at 30 days
R
n1739
Placebo
Primary endpoint occluded artery (TIMI flow
grade TFG 0/1), death/MI by time of angiography
ASA150325 mg (if no ASA within prior 24 hours)
as loading dose. Patients received heparin if
they received a fibrin specific thrombolytic All
patients received ASA 75162 mg/day plus other
standard care
1. Sabatine MS et al. New Engl J Med 2005 352
(available at www.nejm.org)
49
Inclusion/Exclusion Criteria

• Inclusion criteria
• Age 18?75 years
• STEMI within 12 hours
• Planned treatment with fibrinolytic
• Major exclusion criteria
• Clopidogrel within 7 days
• Planned clopidogrel or GPIIb/IIIa before
  angiography
• Contraindications to thrombolysis (stroke, ICH,
  brain tumor)
• Cardiogenic shock
• Intention of angiography within 48 hours
• CABG, creatinine gt2.5 mg/dL, hepatic
  insufficiency, ? platelets
• ?67 kg and gt4000 U bolus UFH gt67 kg and gt5000 U
  bolus gt1.1 mg/kg subcutaneous of enoxaparin

FOR INTERNAL USE ONLY
50
Angiographic Outcomes and Long-term Mortality
HR 0.41 (p0.001)
HR 0.51 (p0.038)
14.5
9.1
2-year mortality ()
6.4
4.8
TFG 0/1
TFG 2/3
TMPG 0/1
TMPG 2/3
TIMI flow grade
TIMI myocardial perfusion grade
90 minute angiogram in TIMI 10b trial HRhazard
ratio
1. Gibson CM et al. Circulation 2002 105
1909?1913.
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Study Endpoints

• Primary endpoint
• Composite
• of occluded infarct related artery (TFG 0/1) on
  pre-discharge angiogram
• Death or MI before CAG
• Death or MI by hospital discharge (maximum 8
  days) if no angiography performed

CV death, MI, stroke or recurrent ischemia
leading to urgent target vessel revascularization
1. Sabatine MS et al. New Engl J Med 2005 352
FOR INTERNAL USE ONLY
52
Clopidogrel Improved Perfusion
25
36 reduction p lt0.001
21.7
20
15.0
15
Primary endpoint ()
10
5
Placebo (n1739)
Clopidogrel (n1752)
Based on odds of an occluded infarct-related
artery (TFG 0/1), death or MI by angiography for
clopidogrel versus placebo (OR 0.64 0.53 to
0.76 p lt0.001)
1. Sabatine MS et al. New Engl J Med 2005 352
(available at www.nejm.org)
53
CLARITY Reduction of Primary Endpoint by 36

• Clopidogrel Placebo Odds ratio
• (n1752) (n1739) (95 CI) p value
• Primary endpoint ()
• TFG 0/1, MI/death 15.0 21.7 0.64
  (0.53?0.76) lt0.001
• Components ()
• TFG 0/1 11.7 18.4 0.59 (0.48?0.72) lt0.001
• Recurrent MI 2.5 3.6 0.70 (0.47?1.04) 0.08
• Death 2.6 2.2 1.17 (0.75?1.82) 0.49

1. Sabatine MS et al. New Engl J Med 2005 352
FOR INTERNAL USE ONLY
54
Primary Endpoint Subgroups
Number of Odds Event rates
() Characteristic patients reduction Clopidogrel
Placebo OVERALL 3491 36 15.0 21.7 Age lt65
years 2466 42 13.2 21.0 ?65 years 1015 22 19.0
23.1 Gender Male 2796 35 14.5 20.8 Female 685 3
8 16.9 24.7 Infarct location Anterior 1416 33 15
.0 20.7 Non-anterior 2065 38 15.0 22.2 Fibrinol
ytic Fibrin-specific 2397 31 14.7 20.1 Non-fibr
in specific 1084 44 15.7 24.9 Predominant
heparin LMWH 1429 31 11.4 15.7 UFH 1431 42 17.8
27.1 None 621 26 17.1 21.9
1.0
0.4
0.6
0.8
1.2
1.6
Clopidogrel better
Placebo better
1. Sabatine MS et al. New Engl J Med 2005 352
55
Clopidogrel Improved Angiographic Outcomes1

• Clopidogrel Placebo Odds ratio
• (n1752) (n1739) (95 CI) p value
• Angiographic outcomes ()
• TFG 3 67.8 60.8 1.36 (1.18?1.57) lt0.001
• TMPG 3 55.8 51.2 1.21 (1.05?1.40) 0.008
• Thrombus 43.0 50.8 0.73 (0.64?0.84) lt0.001

TFG TIMI Flow Grade TPMG TIMI Myocardial
Perfusion Grade
FOR INTERNAL USE ONLY
1. Sabatine MS et al. New Engl J Med 2005 352
(available at www.nejm.org)
56
CLARITY Clinical Events at 30 Days

15
Placebo
20 p0.03
Clopidogrel
10
CV death, MI or recurrent ischemia leading to
urgent revascularization
Incidence of clinical endpoints ()
5
0
0
5
10
15
20
25
30
Time (days)
1. Sabatine MS et al. New Engl J Med 2005
57
Endpoints at 30-Day
Endpoint
Clopidogrel
Placebo
CV death
3
4.4
4.5
Recurrent MI
31
4.1
5.9
Recurrent ischemia
24
3.5
4.5
leading to urgent
revascularization
46
0.9
1.7
Stroke
17
8.4
9.9
CV death or MI
CV death, MI or stroke
18
9.1
10.9
CV death, MI or recurrent
11.6
14.1
ischemia leading to urgent
20
revascularization
CV death, MI, stroke or
21
12.3
15.0
recurrent ischemia leading
to urgent revascularization
1.0
0.4
0.6
0.8
1.2
1.6
Clopidogrel better
Placebo better
1. Sabatine MS et al. New Engl J Med 2005 352
(available at www.nejm.org)
58
Safety

• Clopidogrel Placebo
• (n1733) (n1719) p value
• Primary bleeding endpoint ()
• TIMI major 23 (1.3) 19 (1.1) 0.64
• Secondary bleeding endpoints ()
• TIMI minor 17 (1.0) 9 (0.5) 0.17
• TIMI major or minor 40 (2.3) 28 (1.6) 0.18
• Intracranial hemorrhage 8 (0.5) 12 (0.7) 0.38
• Bleeding through 30 days ()
• TIMI major 33 (1.9) 30 (1.7) 0.80
• TIMI minor 27 (1.6) 16 (0.9) 0.12
• TIMI major or minor 59 (3.4) 46 (2.7) 0.24

1. Sabatine MS et al. New Engl J Med 2005 352
FOR INTERNAL USE ONLY
59
CLARITY Summary

• For STEMI, ASA Lytics loading dose (300mg)
  clopidogrel followed by 75mg OD
• 36 reduction in the odds of an occluded
  infarct-related artery, or death or MI by time of
  pre-discharge angiography or hospital discharge
  (maximum 8 days)
• Consistent across all major subgroups
• At 30 days, a 20 reduction (p0.03) in CV death,
  MI or recurrent ischemia leading to urgent
  revascularization
• No significant excess in TIMI major bleeding or
  ICH

FOR INTERNAL USE ONLY
60
APRICOT
Clarity
TIMI 1
47RR Plt0.001
22RR P0.25
36RR Plt0.001
61
COMMIT/CCS-2 ClOpidogrel and Metoprolol in
Myocardial Infarction Trial
1. Chen ZM et al. ACC 2005.
62
Study Design
Clopidogrel 75 mg QD
(n 23,000)
Patients with acute STEMI ? 24 hours
Double-blind treatment until hospital discharge
or for a maximum of 4 weeks
R
n46,000
(n 23,000)
Placebo
(2 ? 2 Factorial with metoprolol)
All patients received a background of ASA
162mg/day during the study
1. Chen ZM et al. ACC 2005.
63
Inclusion/Exclusion Criteria

• Inclusion Criteria
• Suspected acute MI (with definite ECG changes ST
  Elevation or LBBB)
• 24 h since the onset of symptoms
• No clear indication/contraindication to trial
  treatments
• Exclusion Criteria
• High risk of adverse drug reactions
• Allergy to aspirin or any trial drug
• Active bleeding or haematologic disorder
• Persistent hypotension or bradycardia
• High-degree AV block, pacemaker, cardiogenic
  shock
• Small likelihood of potential benefits
• Low risk of MI death (non-typical MI, primary
  PCI)

FOR INTERNAL USE ONLY
1. Chen ZM et al. ACC 2005.
64
Patient characteristics

• Clopidogrel Placebo
• Characteristic (n22,960) (n22,891)
• Female () 27.7 27.9
• Mean age (yrs) 61.3 61.4
• Age gt70 () 26.0 26.0
• Time from symptom onset
• to randomization (hrs) 10.3 10.3
• Time from symptom onset lt6 h ()
• 33.8 33.7
• Killip class II/III () 24.1 24.0
• STEMI/LBBB 93.1 93.1
• Prior MI history () 8.6 8.1
• Fibrinolytic () 49.7 49.8

FOR INTERNAL USE ONLY
1. Chen ZM et al. ACC 2005.
65
COMMIT Composite Endpoint(Death, MI, or Stroke)
Placebo (10.1)
RRR9 P0.002
10
9
Clopidogrel (9.3)
8
7
6
Events ()
5
4
3
2
1
0
0
7
14
21
28
Days since randomization(up to 28 days)
FOR INTERNAL USE ONLY
1. Chen ZM et al. ACC 2005.
66
COMMIT Mortality
Placebo (8.1)
9
RRR7 p0.03
8
7
Clopidogrel (7.5)
6
5
Mortality ()
4
3
2
1
0
0
7
14
21
28
Days since randomization (up to 28 days)
1. Chen ZM et al. ACC 2005.
67
Clopidogrel Decreased Re-Infarction
13 SE 6 Reduction p0.02
0.4
0.6
0.8
1.0
1.2
1.4
1.6
FOR INTERNAL USE ONLY
1. Chen ZM et al. ACC 2005.
68
Effects of Clopidogrel on Stroke
FOR INTERNAL USE ONLY
1. Chen ZM et al. ACC 2005.
69
Effects of Clopidogrel on Non-Cerebral Bleeding
16 SE 5 Increase P0.004
0.4
0.6
0.8
1.0
1.2
1.4
1.6
Fatal or transfused
FOR INTERNAL USE ONLY
1. Chen ZM et al. ACC 2005.
70
Consistent Effects of Clopidogrel on Death,Re-MI
or Stroke by Age and Gender
FOR INTERNAL USE ONLY
1. Chen ZM et al. ACC 2005.
71
Outcomes by Time Delay and Fibrinolytic Use
1. Chen ZM et al. ACC 2005.
72
COMMIT Summary

• For STEMI, ASA clopidogrel 75mg OD Lytic
• 7 reduction mortality
• No significant excess in TIMI major bleeding or
  ICH

FOR INTERNAL USE ONLY
73
GP IIb/IIIa Receptor Antagonists

• Eptifibatide
• Tirofiban
• Abciximab

74
(No Transcript)
75
(No Transcript)
76
A murine monoclonalantibody that completely
blocks the binding of fibrinogen to platelets
producesa thrombasthenic-like state in normal
platelets and binds to glycoproteinsIIb and/or
IIIa. J Clin Invest 1983 Coller BS, Peerschke
EI, Scudder LE, Sullivan CA.

• Fc fragment of murine monoclonal antibody against
  Gp2b3a, 7E3, was removed to prevent
  immunogenicity and Fab fragments joined with the
  constant regions of human immunoglobulin, forming
  a chimeric compound (abciximab, or c7E3).

77
RGD sequence
78
Gp IIb/IIIa in ACS
79
Gp IIb/IIIa blockers are recommended (Class I)
for UA/NSTEMI treated with interventional
approach. For non-interventional patients with
ongoing ischemia (Class II)
80
ISAR-REACT30-d adverse reactions in
low-to-moderate risk undergoing PCI after 600mg
Clopidogrel loading dose
81
?????????????????
Medical solution
Mechanical solution
82
Percutaneous Coronary Intervention (PCI)
83
Angioplasty Volume in Thailand (Approximate
figures)
Projected for 2004
27 Cath Labs
84
Problems with Angioplasty
Balloon-induced Dissection/ Plaque rupture
Blood-Exposed Non-Intimal Surface (BENIS)
85
Efficacy of Drug Regimens in Coronary Stenting
Ticlopidine ASA
Coumadin ASA
Clopidogrel ASA
12
11
ASA
Clopidogrel LD ASA
8.3
8
6.2
Event rates ( death, MI, revasc.)
5.7
5.6
4
3.6
2.7
1.6
1.5
1.2
0.9
0.5
0
ISAR N517
FANTASTIC N485
STARS N1653
MATTIS N350
CLASSICS N1020
86
Early Discontinuation of Study Drug
28 (8.2)
17 (5.1)
No. of patients discontinuing
7 (2)
87
CREDO

• Symptomatic CAD with objective evidence of
  ischemia
• symptoms of angina pectoris
• positive stress test
• dynamic ECG changes
• referred for elective or urgent PCI
• Randomized to clopidogrel loading (300mg) and
  long term maintenance.

JAMA, November 20, 2002 Vol 288, No 19 2411
2420
88
CREDO
Double-blind, comparison between two
regimens2000 patients, 100 centres in the US
1 MONTH
1 YEAR
PTCA stent
Placebo aspirin
Clopidogrel75 mg aspirin
Placebo aspirin
Group 1
Clopidogrel300 mg LD aspirin
Clopidogrel 75 mg aspirin
Group 2
6-24 h before PTCA stent
89
CREDO

• 300mg clopidogrel vs placebo 3-24hr prior to PCI
• From day 29 to 12months randomized to long term
  clopidogrel vs placebo
• 1 year result 29 reduction in death, MI,
  stroke with loading and long-term clopidogrel.
• Gp IIb/IIIa antagonist had relative benefits in
  the group with gt6-24hr of clopidogrel
  pretreatment.

90
Long-term Benefits of Clopidogrel in PCI Patients
1 year results
(MI, Stroke, or Death)
11.5
27 RRR p 0.02
Standard therapy including ASA JAMA, November
20, 2002 Vol 288, No 19 2411 2420
91
CREDO Results by Subgroups
(MI, Stroke, or Death at 1 year)
Placebo Better
Clopidogrel Better
RRR
GPIIb/IIIa Inhibitor Yes (N826)
No (N1289) ACS Yes (N1407)
No (N694) Diabetes Yes (N560)
No (N1556) Stent Yes (N1616)
No (N500) Male (N1510) Female (N606) Overall (
N2116)
28.8 26.5 27.6 22.7 11.2 32.8 28.8 19.0 24.5 3
2.1 26.9
Hazard ratio (95 CI)
0.6
0.8
1.0
1.2
0.4
JAMA, November 20, 2002 Vol 288, No 19 2411
2420
92
Conclusions

• Antiplatelet therapy is essential in the
  management of patients with ACS
• Medically treated
• Percutaneous intervention
• New studies support expanding role of ADP
  antagonists in the management of STEMI

FOR INTERNAL USE ONLY
1. Chen ZM et al. ACC 2005.
93
Thank you for your attention.