antiplatelet therapy in general overview
DESCRIPTION
Antiplatelet Therapy in General Overview. Prof. Lale Tokgözoğlu MD, FACC, FESC Hacettepe University Faculty of Medicine Department of Cardiology. Cause of Death by Gender in Europe:. WHO 2008. Platelets are important in atherothrombosis. - PowerPoint PPT PresentationTRANSCRIPT
Antiplatelet Therapy in
General Overview
Antiplatelet Therapy in
General Overview
Prof. Lale Tokgözoğlu MD, FACC, FESCHacettepe University Faculty of Medicine
Department of Cardiology
Prof. Lale Tokgözoğlu MD, FACC, FESCHacettepe University Faculty of Medicine
Department of Cardiology
Cause of Death by Gender in Europe:
Cause of Death by Gender in Europe:
WHO 2008
Platelets are important in atherothrombosis
Platelets are important in atherothrombosis
After release from bone marrow, circulate for 7-10 days without interaction with vessel wall
If exposed to subendothelium, platelets activated
After release from bone marrow, circulate for 7-10 days without interaction with vessel wall
If exposed to subendothelium, platelets activated
Unstable plaques activate
platelets
Unstable plaques activate
plateletsPlaqueFissure or Rupture
PlateletAggregation
PlateletActivation
PlateletAdhesion
ThromboticOcclusion
Adhesion
Adhesion mediated by vWF, agonists like ADP, secreted granules and TXA2 cause aggregation, exposed GPIIbIIIa
receptors crosslink with fibrinogen to form platelet aggregates
Adhesion mediated by vWF, agonists like ADP, secreted granules and TXA2 cause aggregation, exposed GPIIbIIIa
receptors crosslink with fibrinogen to form platelet aggregates
Aggregation3
Reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.
1
Activation2
MONOCYTEMONOCYTE
MACROPHAGEMACROPHAGE
THROMBOCYTEAGGREGATIONTHROMBOCYTEAGGREGATION
FIBRINFIBRINTHROMBUSTHROMBUS
SMOOTH MUSCLE CELL SMOOTH MUSCLE CELL
ENDOTHELIUMENDOTHELIUM
THROMBOCYTEADHESIONTHROMBOCYTEADHESION
Platelet surface membrane receptors play important role
Platelet surface membrane receptors play important role
Platelets also important in stent thrombosis:Mechanism of AMI after stent implantation
Platelets also important in stent thrombosis:Mechanism of AMI after stent implantation
Relative frequency
48%
40%
12%
Atherothrombosis at newlocation (after 27 months)
Restenosis (after 19 months)
Stent thrombosis (after 9 months)
Alexopoulos D. Am Heart J 2010; 159: 439-445
Different mechanisms of antiplatelet drugs:Different mechanisms of antiplatelet drugs:1. COX-1 inhibitors
ASA, Omega 3
2. Phosphodiesterase inhibitorsDipyrdamole, Cilostazol
3. ADP-P2Y12 interaction blokersTiclopidine, Clopidogrel, Prasugrel, Cangrelor, Ticagelor
4. GP IIb/IIIa blokers
5. Thrombin receptor antagonists
1. COX-1 inhibitorsASA, Omega 3
2. Phosphodiesterase inhibitorsDipyrdamole, Cilostazol
3. ADP-P2Y12 interaction blokersTiclopidine, Clopidogrel, Prasugrel, Cangrelor, Ticagelor
4. GP IIb/IIIa blokers
5. Thrombin receptor antagonists
AAAA
TxA2TxA2
GPIIb/IIIa
Aggregation
Aspirin
PLATELETPLATELET
Clopidogrel
Prasugrel
Cangrelor Heparin, hirudin
Blocking different pathways for additional clinical benefit:
GP IIb/IIIa antagonists
Epinephrine Collagen
ADP
Epinephrine Collagen
ADP
ASAASA
Inactivates COX irreversibly blocking TXA2 formation (potent mediator of aggregation and vasoconstriction)
Effective 15-30 minutes after oral administration
Large dose over 10 gr eicosapentaenoic acid also blocks TXA2
Inactivates COX irreversibly blocking TXA2 formation (potent mediator of aggregation and vasoconstriction)
Effective 15-30 minutes after oral administration
Large dose over 10 gr eicosapentaenoic acid also blocks TXA2
Phosphodiesterase InhibitorsPhosphodiesterase Inhibitors
Dipyridamole stimulates PGI2 synthesis, blocks uptake of adenosine
Clinical trials failed to show efficacy alone, enhances warfarin and ASA
MR form useful for stroke prevention Cilostazol may be useful in claudicatio
and has vasodilatory and antiplatelet effects
Dipyridamole stimulates PGI2 synthesis, blocks uptake of adenosine
Clinical trials failed to show efficacy alone, enhances warfarin and ASA
MR form useful for stroke prevention Cilostazol may be useful in claudicatio
and has vasodilatory and antiplatelet effects
ThienopyridinesThienopyridines Bind to P2Y12
receptor inhibiting interaction with ADP that would result in activation and aggregation
Prodrugs requiring transformation to active metabolites
Bind to P2Y12 receptor inhibiting interaction with ADP that would result in activation and aggregation
Prodrugs requiring transformation to active metabolites
Ticlopidine dramatically changed interventional cardiology by making stent implantation safe
Ticlopidine dramatically changed interventional cardiology by making stent implantation safe
0
2
4
6
8
10
12
14
Prim. Cardiac EP Abrupt vesselclosure
Prim. NoncardiacEP
Bleeding
Ticlo + ASA UFH + Warfarin + ASA
0
2
4
6
8
10
12
14
Prim. Cardiac EP Abrupt vesselclosure
Prim. NoncardiacEP
Bleeding
Ticlo + ASA UFH + Warfarin + ASA
Schomig, NEJM 1996
Ticlopidine replaced by clopidogrel: more effective, safer
Ticlopidine replaced by clopidogrel: more effective, safer
0
1
2
3
4
5
MACE Mortality
Ticlopidine
Clopidogrel
0
1
2
3
4
5
MACE Mortality
Ticlopidine
Clopidogrel
Bhatt, JACC 2002
Antiplatelet Resistance:Antiplatelet Resistance: Genetic polymorphism in platelet proteins
(CYP2C19 reduced function alleles have 30 % decrease in active clopidogrel)
Drug interaction (NSAID , drugs metabolized with Cytochrome P450 )
Environmental factors(Smoking, DM, HTN, HLP, ACS)
VARIABILITY IN RESPONSE NOT ALWAYS RESISTANCE:
Insufficent dosing, differences in assays and cutoffs, no gold standart
Genetic polymorphism in platelet proteins (CYP2C19 reduced function alleles have 30 % decrease in active clopidogrel)
Drug interaction (NSAID , drugs metabolized with Cytochrome P450 )
Environmental factors(Smoking, DM, HTN, HLP, ACS)
VARIABILITY IN RESPONSE NOT ALWAYS RESISTANCE:
Insufficent dosing, differences in assays and cutoffs, no gold standart
Is Aspirin Resistance Clinically Significant?
Is Aspirin Resistance Clinically Significant?
JACC 2003:41; 961JACC 2003:41; 961Circulation 2002, 105: 1650
326 stable CAD 5.2 % Aspirin resistance In HOPE study, @ 5 year follow up
MI, stroke, death rate 1.8 % increased in the group with 11- deoxythromboxane B2 level !
326 stable CAD 5.2 % Aspirin resistance In HOPE study, @ 5 year follow up
MI, stroke, death rate 1.8 % increased in the group with 11- deoxythromboxane B2 level !
ASA resistance vs. clopidogrel resistance vs. dual resistanceASA resistance vs. clopidogrel resistance vs. dual resistance
The prevalence of drug resistance: ASA 16%, CLOPI 15%, dual 9%The risk is 7x higher with dual resistence and 4.5x higher with multivessel PCI
Eshtehardi P, Am Heart J 2010; 159: 891-898
26%
37%
5
10
15
20
25
30
35
40
Periprocedur.MI Ischaemic events within 30 days
No resistance
ASA resistance
CLOPI resistance
Dual resistance
0
Per
cen
tag
eP
erce
nta
ge
Definition of Resistance Varies with Method Used: ASA Resistance Measured
by PFA-100 and Aggregometry
Definition of Resistance Varies with Method Used: ASA Resistance Measured
by PFA-100 and Aggregometry
23.8 %
5.5 %
70.7 % Aspirin Sensitive
RESISTANTRESISTANT
Partial responsePartial response
9.5 %
90.5 %Aspirin Resistant
Stable AP n= 325 patients
AggregometryResponse to ADP and AA
AggregometryResponse to ADP and AA
PFA-100PFA-100
Gum P. Am J Cardiol 2001;88:230-235
Routine assessment of platelet aggregation not recommended (II-B)
Routine assessment of platelet aggregation not recommended (II-B)
Zidar F, et al. J Am Coll Cardiol. 2004;43(5, suppl A);Abstract 1100-1159.
Ag
gre
gat
ion
inh
ibit
ion
(%
)A
gg
reg
atio
n in
hib
itio
n (
%)
Clopidogrel, 600 mgClopidogrel, 600 mgClopidogrel, 300 mgClopidogrel, 300 mg
*P=0.01** P=0.02
‡ P=0.0008
* **‡
*
**
0
60
40
20
80
0 2 4 6
HoursHours
600 mg clopidogrel loading is faster and more effective !
600 mg clopidogrel loading is faster and more effective !
ARMYDA-IIARMYDA-II
Circulation 2005;111:2099Circulation 2005;111:2099
Doubling loading and maintenance dose of clopidogrel in ACS patients undergoing PCIDoubling loading and maintenance dose of clopidogrel in ACS patients undergoing PCI
CV death, MI or stroke
Days
0 3 6 9 12 15 18 21 24 27 30
Clopidogrel standard
Clopidogrel double
HR 0.8595% CI: 0.74-0.99p=0.036
15% RRR
Cu
mu
lati
ve h
azar
dC
um
ula
tive
haz
ard
0.000.00
0.010.01
0.020.02
0.030.03
0.040.04
-20
0
20
40
60
80
100
Clopidogrel to Prasugrel Crossover Study: Less variability with prasugrel since it produces
higher concentrations of active metabolite
Clopidogrel to Prasugrel Crossover Study: Less variability with prasugrel since it produces
higher concentrations of active metabolite
IPA (20 µM ADP) 24 hours
Healthy volunteers Crossover study
Clopidogrel reply Prasugrel reply
Pla
tele
t ag
gre
gat
ion
in
hb
itio
n (
%)
Clopidogrel effective
Clopidogrel resistant
N=66
Brandt et al. J Am Coll Cardiol 2005;45(3 Suppl 1):87A – abstract 868-5
TRITON-TIMI 38: 13608 patients with ACS
TRITON-TIMI 38: 13608 patients with ACS
Key safety end point: non-CABG related TIMI Major Bleeding
& Planned PCI
ASA
ASA
Primary efficacy end point: a composite of the rate of death from cardiovascular causes, nonfatal MI, or nonfatal stroke
=
UA/NSTEMI (TIMI Risk Score ≥ 3)
STEMI (Primary PCI ≤ 12 hours of symptoms or post-STEMI within 14 days)
RD
ay 3
Day
30
Day
90
Prasugrel60 mg LD/ 10 mg MD
Clopidogrel300 mg LD/ 75 mg MD
Day
450
Key secondary end points at 30 and 90 days included primary efficacy end point and a composite of the rate of death from cardiovascular causes, nonfatal MI, or UTVR
=
14.5 month actual median
12.0 month planned median
Double-blind treatment 6 - 15 months planned
follow-up
Wiviott SD et al. New Engl J Med 2007;357:2001-2015; Wiviott SD et al. Am Heart J 2006;152:627-635
TRITON TIMI-38:TRITON TIMI-38: Balance of efficacy and safety in patients Balance of efficacy and safety in patients
< 75 Yrs, ≥ 60 kg, and without prior TIA/Stroke (N=10,804) < 75 Yrs, ≥ 60 kg, and without prior TIA/Stroke (N=10,804)
0
2
4
6
8
10
12
14
16
0 30 90 180 270 360 450
En
dp
oin
t (%
)
HR 1.24(95% CI: 0.91-1.69)p=0.17, NNH 222
HR 0.74(95% CI: 0.66-0.84)p<0.001, NNT 37
Clopidogrel 11.0%
Prasugrel 8.3%
Clopidogrel 1.5%
Prasugrel 1.9%
Days
CV death, NF MI, or NF stroke
TIMI major bleeding
Wiviott SD et al. Circulation 2010;122:394-403
Prevention of bleeding just as important as prevention of ischemia:
Prevention of bleeding just as important as prevention of ischemia:
SafetySafety
EfficacyEfficacy
In Clopidogrel group ,30 % of subjects had reduced function allele for CYP, these had 3X more stent
thrombosis
In Clopidogrel group ,30 % of subjects had reduced function allele for CYP, these had 3X more stent
thrombosis
Genetic and Platelet Fx Tests are Complementary
Genetic and Platelet Fx Tests are Complementary
Genome
Transcriptome
Proteome
Phenotype
EnvironmentGenetics
Platelet function testing
Variable Response to ClopidogrelVariable Response to Clopidogrel
Test: Increase dose
Alternative treatment:Genetic,
platelet function
+ Personalise
- Complex
+ Easy
- Efficacy, safety ?
+ Efficacy- Cost ? Bleeding ?
Patients undergoing PCI with high platelet activity randomised to 75 mg C or 600 loading plus 150 mg C: GRAVITAS Study
End point High-dose clopidogrel (%)
Standard-dose clopidogrel (%)
HR (95% CI) p
Cardiovascular death/MI/stent thrombosis
2.3 2.3 1.01 (0.58-1.76) 0.98
Primary end point
Bleeding results Outcome High-dose
clopidogrel (%)Standard-dose clopidogrel (%)
p
GUSTO severe/moderate bleeding 1.4 2.3 0.10
Any GUSTO bleeding 12.0 10.2 0.18
Percentage of patients with persistently high platelet reactivity at 30 days Platelet reactivity units High-dose
clopidogrel (%)Standard-dose clopidogrel (%) p
>230 62 40 <0.001
AHA 2010
CangrelorCangrelor Potent inhibitor of ADP
induced aggregation ATP analogue that inhibits
P2Y12 by 100 % No renal/hepatic
metabolism to be activated İv,rapid action, platelets
back to normal in 60 minutes
Has additive effects to clopidogrel
Two short term trials discontinued for less than expected efficacy
Potent inhibitor of ADP induced aggregation
ATP analogue that inhibits P2Y12 by 100 %
No renal/hepatic metabolism to be activated
İv,rapid action, platelets back to normal in 60 minutes
Has additive effects to clopidogrel
Two short term trials discontinued for less than expected efficacy
TicagrelorTicagrelor
Stable, high affinity inhibitor of ADP induced aggregation
Oral agent acting directly on P2Y12 receptor without transformation
Rapid and greater action Reversibility 180 mg loading ,90 mg bid Higher doses cause dyspnea and
ventricular pause
Stable, high affinity inhibitor of ADP induced aggregation
Oral agent acting directly on P2Y12 receptor without transformation
Rapid and greater action Reversibility 180 mg loading ,90 mg bid Higher doses cause dyspnea and
ventricular pause
PLATO StudyPLATO Study . Lancet. 2002;359:189-198 . Lancet. 2002;359:189-198
NEJM 2009; 361:1045
Glycoprotein IIb/IIIa Inhibitors Block the Common Final Pathway to Platelet Aggregation
regardless of the stimulus for activation
Glycoprotein IIb/IIIa InhibitorsGlycoprotein IIb/IIIa Inhibitors
Monoclonal Ab against IIb/IIIa: Abciximab
Peptide antagonist: Eptifibatid Nonpeptide antagonist: Tirofiban
Monoclonal Ab against IIb/IIIa: Abciximab
Peptide antagonist: Eptifibatid Nonpeptide antagonist: Tirofiban
GP IIb/IIIa Inhibitors in ACS:30 day death / MI (N=31,402) GP IIb/IIIa Inhibitors in ACS:30 day death / MI (N=31,402)
PRISMPRISM 7.1%7.1% 5.8%*5.8%* 0.800.80 0.60-1.060.60-1.06
PRISM-PLUSPRISM-PLUS 12.0%12.0% (*)(*) 8.7%8.7% 0.700.70 0.50-0.980.50-0.98((† )) 13.6%*13.6%* 1.171.17 0.80-1.700.80-1.70
PARAGON-APARAGON-A 11.7%11.7% (l)(l) 10.3%10.3% 0.870.87 0.58-1.290.58-1.29(h)(h) 12.3%12.3% 1.061.06 0.72-1.550.72-1.55
PURSUITPURSUIT 15.7%15.7% (l)(l) 13.4%13.4% 0.830.83 0.70-0.990.70-0.99(h)(h) 14.2%14.2% 0.890.89 0.79-1.000.79-1.00
PARAGON-BPARAGON-B 11.4%11.4% 10.6%10.6% 0.920.92 0.77-1.090.77-1.09
GUSTO-IVGUSTO-IV 8.0%8.0% (24h)(24h) 8.2%8.2% 1.021.02 0.83-1.240.83-1.24(48h)(48h) 9.1%9.1% 1.151.15 0.94-1.390.94-1.39
OverallOverall 11.8%11.8% 10.8%10.8%tt 0.910.91 0.85-0.980.85-0.98
Odds RatioPlacebo Gp IIb/IIIa 95% CI
Placebo iyiGp IIb/IIIa iyi
0 1.0 2.0
Study
P=.015
Boersma E, et al. Lancet. 2002;359:189-198.
-High risk
- Diabetic
- ASA use on admission
PRISM-PLUS: Thrombus sizePRISM-PLUS: Thrombus size
0
10
20
30
40
50
Heparin(n=622)
Big
Tirofiban + Heparin(n=608)
Probable
Small
Medium
Probable
Small
Medium
Odds Ratio: 0.77
P=0.022
17.1%
24.1%
Big
Occlusion Occlusion
Circulation. 1999;100:1609-1615.
Cumulative (%)
ACUITY, timing GP IIb/IIIa at the time of PCI vs. upstream in everyone
ACUITY, timing GP IIb/IIIa at the time of PCI vs. upstream in everyone
Stone GW et al. JAMA 2007;297:591-602
Routine Upstream GP IIb/IIIa(N=4,605)
Deferred PCIGP IIb/IIIa(N=4,602)
98.3% 55.7%
6.2 6.2
0.6 4.6
11.7 11.7
7.1 7.9
6.1 4.9
Ischaemic EP
Net clinical benefit
Bleeding EP
Rand. to GP IIb/IIIa (h)
Rand. to angio/interv (h)
Overall exposure
DaysDays
6 months death/MI
15.5%15.5%
10.9%10.9%
8.4%8.4%7.2%7.2%
Chan A, et al. J Am Coll Cardiol. 2003;42:1188-1195.
TARGET: Benefit of triple antiplatelet therapy
TARGET: Benefit of triple antiplatelet therapy
Patients(%)
Patients(%)
No clopidogrel only tirofibanNo clopidogrel only abciximab
Clopidogrel and tirofibanClopidogrel and abciximab18
16
14
12
10
8
6
4
2
00 30 60 90 120 150 180
Relation between age, dosing and bleedingRelation between age, dosing and bleeding
Age
Ex
ces
s d
ose
%E
xce
ss
do
se %
Ex
ces
s d
ose
%E
xce
ss
do
se %
Ma
jor
ble
ed
ing
%M
ajo
r b
lee
din
g %
Ma
jor
ble
ed
ing
%M
ajo
r b
lee
din
g %
Eur Heart J Suppl 2007, 9 (Suppl A) A23-A31.Eur Heart J Suppl 2007, 9 (Suppl A) A23-A31.
Antithrombotic treatment options in myocardial revascularisation: STEMIAntithrombotic treatment options in myocardial revascularisation: STEMI
Antiplatelet therapy Classa Levelb
ASA I B
Clopidogrelc (with 600 mg loading dose as soon as possible) I C
Prasugreld I B
Ticagrelord I B
+ GPIIb–IIIa antagonists (in patients with evidence of high intracoronary thrombus burden)
Abciximab IIa A
Eptifibatide IIa B
Tirofiban IIb B
Upstream GPIIb–IIIa antagonists III B
Anticoagulation
Bivalirudin (monotherapy) I B
UFH I C
Fondaparinux III Ba: Class of recommendation; b: Level of evidence; c: Primarily if more efficient antiplatelet agents are contraindicated; d: Depending on approval and availability. Direct comparison between prasugrel and ticagrelor is not available. Long term follow-up is awaited for both drugs
a: Class of recommendation; b: Level of evidence; c: Primarily if more efficient antiplatelet agents are contraindicated; d: Depending on approval and availability. Direct comparison between prasugrel and ticagrelor is not available. Long term follow-up is awaited for both drugs
Eur Heart J 2010. On lineEur Heart J 2010. On line
Antithrombotic treatment options in myocardial revascularisation: NSTE-ACS
Antithrombotic treatment options in myocardial revascularisation: NSTE-ACS
Antiplatelet therapy Classa Levelb
ASA I C
Clopidogrelc (with 600 mg loading dose as soon as possible) I C
Clopidogrelc (for 9–12 months after PCI) I B
Prasugreld IIa B
Ticagrelord I B
+ GPIIb–IIIa antagonists (in patients with evidence of high intracoronary thrombus burden)
Abciximab (with DAPT) II B
Tirofiban, Eptifibatide IIa B
Upstream GPIIb–IIIa antagonists III B
a: Class of recommendation; b: Level of evidence; c: Primarily if more efficient antiplatelet agents are contraindicated; d: Depending on approval and availability. Direct comparison between prasugrel and ticagrelor is not available. Long term follow-up is awaited for both drugs
a: Class of recommendation; b: Level of evidence; c: Primarily if more efficient antiplatelet agents are contraindicated; d: Depending on approval and availability. Direct comparison between prasugrel and ticagrelor is not available. Long term follow-up is awaited for both drugs
Eur Heart J 2010. On lineEur Heart J 2010. On line
Antiplatelets for ischemic stroke or preventing systemic embolismAntiplatelets for ischemic stroke or preventing systemic embolism
Camm, ESC 2009
Warfarin vs placebo
Warfarin vs low dose Warfarin
Warfarin vs ASA
Warfarin vs ASA + clopidogrel
Warfarin better Other better
0 0.3 0.6 0.9 1.2 1.5 1.8 2.0
What is the ideal antiplatelet drug?
What is the ideal antiplatelet drug?
Effective platelet inhibition without bleeding Uniformly effective in all patients (no resistance) Simple dosage No side effects No drug interactions Reasonable price
FOR NOW: Beware of drug interactions and bleeding Keep ASA dose low in combination Calculate GPI dose meticulously
Effective platelet inhibition without bleeding Uniformly effective in all patients (no resistance) Simple dosage No side effects No drug interactions Reasonable price
FOR NOW: Beware of drug interactions and bleeding Keep ASA dose low in combination Calculate GPI dose meticulously
New Horizons in Antiplatelet Therapy:
New Horizons in Antiplatelet Therapy:
- TRA thrombin receptor antagonists
- Antagonists to A1 domain on vWF: ARC1779
- Collagen induced platelet aggregation blockers : CTRP-1
- TRA thrombin receptor antagonists
- Antagonists to A1 domain on vWF: ARC1779
- Collagen induced platelet aggregation blockers : CTRP-1
TRITON-TIMI 38: Therapeutic considerations for
subgroups
TRITON-TIMI 38: Therapeutic considerations for
subgroups
Majority of patients:Significant benefit with prasugrel 10 mg (MD)
Age ≥75 years or weight <60 kg:Prasugrel 10 mg equivalent to clopidogrel(Prasugrel 5 mg under investigation)
Prior stroke/TIA:Prasugrel is
contraindicated
80%
4%
16%
PRAGUE-8 (with 600 mg load): Patients undergoing elective PCIPRAGUE-8 (with 600 mg load):
Patients undergoing elective PCI
Widimsky P et al. Eur Heart J 2008;29:1495-1503
Pre-treatment Clop 600 mg(n=155)
No Pre-treatmentClop 600 mg(n=143)
0
20
D/MI/CVA/UTVR Troponin >3XULN Major + MinorBleeding
p=NS
p=NS
p=0.0068.4
2.8
11.9
1.3
10
15
5
7.1
0.7
Per
cen
tag
e p
atie
nts
Activated platelets express CD 40L triggering inflammation and thrombosis
Activated platelets express CD 40L triggering inflammation and thrombosis
ISAR-CHOICEISAR-CHOICE
Circulation 2005;112:2946Circulation 2005;112:2946
30th DAY DEATH / MI WITH GPI%
Par
ient
s
10.9
1.8
9
4.8
10.1
3.6
14.1
3.9
10.2
5.9
16.7
11.6
0
2
6
10
14
18
EPIC CAPTURE EPILOG EPISTENT PRISM-PLUS PURSUIT
Placebo GP IIb-IIIa Inhibitor
Klopidogrel Prasugrel
300/75 40/7.5 60/10 60/15
JUMBO - TIMI 26 (Phase II)PCI + Stent (n= 904)
ASA 325 + % 70 GP2b/3a
JUMBO - TIMI 26 (Phase II)PCI + Stent (n= 904)
ASA 325 + % 70 GP2b/3a
Clopidogrel Prasugrel
300/75 40/7.5 60/10 60/15
Circulation 2005;111:3366Circulation 2005;111:3366
1,2
1,7
0
1
2
Major, minor bleeding
1,2
1,7
0
1
2
Major, minor bleeding
9,4
7,2
0
5
10
MACE
9,4
7,2
0
5
10
MACE
%%%%
Variable Clopidogrel Response Variable Clopidogrel Response At 5 Days
UA Patients* (n = 32)
At 5 DaysUA Patients* (n = 32)
Responders47%
Low responders32%
Nonresponders22%
*Received an oral loading dose of 300 mg of clopidogrel followed by 75 mg daily.Gurbel PA, et al. Circulation. 2003;107(23):2908-2913; Lau WC, et al. Circulation. 2004;109(2):166-171.