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New Treatment AdvancesNew Treatment Advancesin Acute Coronaryin Acute CoronarySyndromeSyndrome
ObjectivesObjectives
• Establish that ACS (unstable angina/non–ST-Establish that ACS (unstable angina/non–ST-elevation MI) is a high-risk conditionelevation MI) is a high-risk condition
• Present the identified barriers to GP IIb/IIIa usePresent the identified barriers to GP IIb/IIIa use
• Identify patients that benefit from GP IIb/IIIa therapyIdentify patients that benefit from GP IIb/IIIa therapy
• Conclusion:Conclusion:
– Establish the need and rationale for early treatment Establish the need and rationale for early treatment with GP IIb/IIIa therapywith GP IIb/IIIa therapy
Risk of ACSRisk of ACSClinical Outcomes at 30 Days in Standard Care ArmClinical Outcomes at 30 Days in Standard Care Arm
15.7%
11.9%
11.7%
8.98%
7.7%
0 5 10 15 20
PURSUIT
PRISM-PLUS
PARAGON
CAPTURE
ESSENCE
Risk of Death or MIRisk of Death or MI
Cohen M, et al. Cohen M, et al. N Engl J MedN Engl J Med. 1997;337:447–452.. 1997;337:447–452.
Kong DF, et al. Kong DF, et al. CirculationCirculation. 1998;98:2829–2835.. 1998;98:2829–2835.
GP IIb/IIIa Inhibitor Utilization in GP IIb/IIIa Inhibitor Utilization in 19991999
7%
93%IIb/IIIaNo IIb/IIIa
PCI ACS
Internal Merck Market Research, 1999.
54%
46%
The Role of Platelets in ACSThe Role of Platelets in ACS
Recruitment Recruitment and Activationand Activation
Adapted from Schafer AI. Adapted from Schafer AI. Am J MedAm J Med. 1996;101:199–209.. 1996;101:199–209.
AdhesionAdhesion AggregationAggregation
Fibrin Fibrin strandstrand
PlateletsPlatelets
SubendotheliumSubendotheliumexposedexposed
ADPADPTXATXA22
GP IIb/IIIa Receptor Activation GP IIb/IIIa Receptor Activation PathwaysPathways
Current Limitations to the Use of Current Limitations to the Use of GP IIb/IIIa Inhibitors GP IIb/IIIa Inhibitors
• Physician perceptionsPhysician perceptions
– No incremental benefit beyond ASA-heparinNo incremental benefit beyond ASA-heparin
– Bleeding risk is unacceptableBleeding risk is unacceptable
• Not sure how patients will be treated: PTCA, Not sure how patients will be treated: PTCA, CABG, medical therapyCABG, medical therapy
• Use of LMWHUse of LMWH
• Not sure Not sure whomwhom to treat or to treat or whenwhen to treat to treat
Current Limitations to the Use of Current Limitations to the Use of GP IIb/IIIa Inhibitors GP IIb/IIIa Inhibitors
• Physician perceptionsPhysician perceptions
– No incremental benefit beyond ASA-heparinNo incremental benefit beyond ASA-heparin
– Bleeding risk is unacceptableBleeding risk is unacceptable
• Not sure how patients will be treated: PTCA, Not sure how patients will be treated: PTCA, CABG, medical therapyCABG, medical therapy
• Use of LMWHUse of LMWH
• Not sure Not sure whomwhom to treat or to treat or whenwhen to treat to treat
Risk of ACSRisk of ACSClinical Outcomes at 30 Days in Standard Care ArmClinical Outcomes at 30 Days in Standard Care Arm
15.7%
11.9%
11.7%
8.98%
7.7%
0 5 10 15 20
PURSUIT
PRISM-PLUS
PARAGON
CAPTURE
ESSENCE
Risk of Death or MIRisk of Death or MI
Cohen M et al. Cohen M et al. N Engl J MedN Engl J Med. 1997:337:447–452.. 1997:337:447–452.
Kong DF et al. Kong DF et al. CirculationCirculation. 1998;98:2829–2835.. 1998;98:2829–2835.
Inclusion CriteriaInclusion Criteria
– Prolonged anginal pain at rest during previous 12 hours andProlonged anginal pain at rest during previous 12 hours and
– New transient or persistent ST-T changes orNew transient or persistent ST-T changes or
– Elevation of CK and CK-MBElevation of CK and CK-MB
Selected Exclusion CriteriaSelected Exclusion Criteria
– Patients with current or recent history of bleeding eventsPatients with current or recent history of bleeding events
– High blood pressureHigh blood pressure
– Persistent ST-elevationPersistent ST-elevation
Entry Criteria, Exclusion Criteria and Study Entry Criteria, Exclusion Criteria and Study Design: PRISM-PLUSDesign: PRISM-PLUS
PTCA
48 hour StudyDrug Theapy
ContinuedMedical Therapy
Presentation
Angiography(90% of Patients) CABG
The PRISM-PLUS Study Investigators. The PRISM-PLUS Study Investigators. N Engl J MedN Engl J Med. 1998;338:1488–1497.. 1998;338:1488–1497.
Inclusion CriteriaInclusion Criteria
– Prolonged anginal pain at rest during previous 24 hours andProlonged anginal pain at rest during previous 24 hours and
– New transient or persistent ST-T changes orNew transient or persistent ST-T changes or
– Elevation of CK-MBElevation of CK-MB
Selected Exclusion CriteriaSelected Exclusion Criteria
– Patients with current or recent history of bleeding eventsPatients with current or recent history of bleeding events
– High blood pressureHigh blood pressure
– Persistent ST-elevationPersistent ST-elevation
Entry Criteria, Exclusion Criteria and Study Entry Criteria, Exclusion Criteria and Study Design: PURSUITDesign: PURSUIT
ContinuedMedical Therapy
Presentation
± Angiography
PTCA
CABG
Infusion of Study Drug
PURSUIT Trial Investigators. PURSUIT Trial Investigators. N Engl J Med.N Engl J Med. 1998;339:436–443. 1998;339:436–443.
0
5
10
15
20
25
2 Days 7 Days (primary endpoint)
30 Days
RR=32%RR=32%PP=0.004=0.004
17.9
12.9
RR=22%RR=22%PP=0.029=0.029
22.3
18.5
% P
atie
nts
% P
atie
nts
The PRISM-PLUS Study Investigators. The PRISM-PLUS Study Investigators. N Engl J MedN Engl J Med. 1998;338:1488. 1998;338:1488–1497.1497.
Heparin (n=797)
AGGRASTAT® (tirofiban HCl) + Heparin (n=773)
NSNSPP=0.08=0.08
7.85.7
PRISM-PLUS: Composite MI/Death/Refractory PRISM-PLUS: Composite MI/Death/Refractory Ischemia Event Rates at 2, 7, and 30 DaysIschemia Event Rates at 2, 7, and 30 Days
0
5
10
15
2 Days 7 Days 30 Days
RR=43%P=0.006
8.3
4.9
RR=30%P=0.03
11.9
8.7
% P
atie
nts
% P
atie
nts
The PRISM-PLUS Study Investigators. The PRISM-PLUS Study Investigators. N Engl J MedN Engl J Med. 1998;338:1488. 1998;338:1488–1497.1497.
Heparin (n=797)
AGGRASTAT® (tirofiban HCl) + Heparin (n=773)
RR=66%P=0.01
2.6
0.9
PRISM-PLUS: Combined MI/Death Event PRISM-PLUS: Combined MI/Death Event Rates at 2, 7, and 30 DaysRates at 2, 7, and 30 Days
The PRISM-PLUS Study Investigators. The PRISM-PLUS Study Investigators. N Engl J MedN Engl J Med. 1998;338:1488. 1998;338:1488–1497.1497.
RR=32%P=0.004
Composite Endpoint
RefractoryIschemia
MI/Death
RR=30%P=0.02
RR=47%P=0.006
RR=43%P=0.006
MI
P=0.99
Death
% P
ati
ents
% P
ati
ents
Heparin (N=797)
AGGRASTAT® (tirofiban HCI)+ Heparin (N=773)
0
5
10
15
20
PRISM-PLUS:PRISM-PLUS:Event Rates at 7 DaysEvent Rates at 7 Days
PURSUIT Trial: 96 hrs, 7 and 30 Day Rates of PURSUIT Trial: 96 hrs, 7 and 30 Day Rates of MI/DeathMI/Death
9.1
11.6
15.7
7.6
10.1
14.2
0
2
4
6
8
10
12
14
16
18
96 Hours 7 Days 30 Days
Eve
nt
Rat
e %
Ch
ang
e
PlaceboEptifibatide
PURSUIT Investigators. PURSUIT Investigators. N Engl J Med.N Engl J Med. 1998;339:436 1998;339:436–443. Adapted from Table 2.443. Adapted from Table 2.
P = 0.04
P = 0.02
P = 0.01
(Primary Endpoint)
Conclusion:Conclusion:
• PRISM-PLUS (tirofiban) demonstrated a significant PRISM-PLUS (tirofiban) demonstrated a significant reduction in the primary endpoint.reduction in the primary endpoint.
• PURSUIT (eptifibatide) demonstrated a significant PURSUIT (eptifibatide) demonstrated a significant reduction in the primary endpoint.reduction in the primary endpoint.
• Short-acting GP IIb/IIIa Inhibitors reduce events in Short-acting GP IIb/IIIa Inhibitors reduce events in unstable angina/nonunstable angina/non––Q-wave MI patients.Q-wave MI patients.
Current Limitations to the Use of Current Limitations to the Use of GP IIb/IIIa Inhibitors GP IIb/IIIa Inhibitors
• Physician perceptionsPhysician perceptions
– No incremental benefit beyond ASA-heparinNo incremental benefit beyond ASA-heparin
– Bleeding risk is unacceptableBleeding risk is unacceptable
• Not sure how patients will be treated: PTCA, Not sure how patients will be treated: PTCA, CABG, medical therapyCABG, medical therapy
• Use of LMWHUse of LMWH
• Not sure Not sure whomwhom to treat or to treat or whenwhen to treat to treat
Major Bleeding (TIMI)
Minor Bleeding (TIMI)
Transfusions (all blood products)
Platelets 90,000/mm3
1.4%
10.5%
4.0%
1.9%
0.8%
8.0%
2.8%
0.8%
AGGRASTATAGGRASTAT ®®
(tirofiban HCl) + Heparin(tirofiban HCl) + Heparinn=773n=773
HeparinHeparinn=797n=797
PRISM-PLUS: Hematologic PRISM-PLUS: Hematologic ComplicationsComplications
The PRISM-PLUS Study Investigators. The PRISM-PLUS Study Investigators. N Engl J MedN Engl J Med. 1998;338:1488-1497.. 1998;338:1488-1497.
nn %%
AGGRASTAT AGGRASTAT ®® (tirofiban HCl) (tirofiban HCl) + Heparin+ Heparin HeparinHeparin
nn %%
Prior to procedures 2/773 0.3 1/797 0.1
Following angiography 9/697 1.3 5/708 0.7
Following PTCA 6/239 2.5 5/236 2.2
Patients undergoing 5/29 17.2 11/31 35.4CABG*
* Within 1 day after discontinuation of AGGRASTAT.
PRISM-PLUS: Incidence of TIMI PRISM-PLUS: Incidence of TIMI Major Bleeding in Patients Undergoing Major Bleeding in Patients Undergoing
Interventional ProceduresInterventional Procedures
Indications for AGGRASTAT® Indications for AGGRASTAT® (tirofiban HCl)(tirofiban HCl)
• AGGRASTAT, in combination with heparin, is AGGRASTAT, in combination with heparin, is indicated for the treatment of ACS, including indicated for the treatment of ACS, including patients who are to be managed medically and patients who are to be managed medically and those undergoing PTCA or atherectomy. In this those undergoing PTCA or atherectomy. In this setting, AGGRASTAT has been shown to decrease setting, AGGRASTAT has been shown to decrease the rate of a combined endpoint of death, new MI, the rate of a combined endpoint of death, new MI, or refractory ischemia/repeat cardiac procedureor refractory ischemia/repeat cardiac procedure
Contraindications for AGGRASTATContraindications for AGGRASTAT® ®
(tirofiban HCl)(tirofiban HCl)AGGRASTAT is contraindicated in patients withAGGRASTAT is contraindicated in patients with
• Known hypersensitivity to any component of the productKnown hypersensitivity to any component of the product
• Active internal bleeding or a history of bleeding diathesis within the previous Active internal bleeding or a history of bleeding diathesis within the previous 30 days30 days
• History of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or History of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysmaneurysm
• History of thrombocytopenia following prior exposure to AGGRASTATHistory of thrombocytopenia following prior exposure to AGGRASTAT
• History of stroke within 30 days or any history of hemorrhagic strokeHistory of stroke within 30 days or any history of hemorrhagic stroke
• Major surgical procedure or severe physical trauma within the previous monthMajor surgical procedure or severe physical trauma within the previous month
• History, symptoms, or findings suggestive of aortic dissectionHistory, symptoms, or findings suggestive of aortic dissection
• Severe hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 Severe hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg)mmHg)
• Concomitant use of another parenteral GP IIb/IIIa inhibitorConcomitant use of another parenteral GP IIb/IIIa inhibitor
• Acute pericarditisAcute pericarditis
Laboratory MonitoringLaboratory Monitoring
• Platelet counts, hemoglobin, and hematocrit should be monitored Platelet counts, hemoglobin, and hematocrit should be monitored prior to treatment, within 6 hours following the loading infusion, prior to treatment, within 6 hours following the loading infusion, and at least daily thereafter during therapy with AGGRASTATand at least daily thereafter during therapy with AGGRASTAT®® (tirofiban HCl).(tirofiban HCl).
• If the patient experiences a platelet decrease to If the patient experiences a platelet decrease to <90,000/mm<90,000/mm33, additional platelet counts should be performed to , additional platelet counts should be performed to exclude pseudothrombocytopenia.exclude pseudothrombocytopenia.
• If thrombocytopenia is confirmed, AGGRASTAT and heparin should If thrombocytopenia is confirmed, AGGRASTAT and heparin should be discontinued and the condition appropriately monitored and be discontinued and the condition appropriately monitored and treated.treated.
• To monitor unfractionated heparin, aPTT should be monitored 6 To monitor unfractionated heparin, aPTT should be monitored 6 hours after the start of heparin infusion; heparin should be hours after the start of heparin infusion; heparin should be adjusted to maintain aPTT at approximately 2 times control.adjusted to maintain aPTT at approximately 2 times control.
Current Limitations to the Use of Current Limitations to the Use of GP IIb/IIIa Inhibitors GP IIb/IIIa Inhibitors
• Physician perceptionsPhysician perceptions
– No incremental benefit beyond ASA-heparinNo incremental benefit beyond ASA-heparin
– Bleeding risk is unacceptableBleeding risk is unacceptable
• Not sure how patients will be treated: PTCA, Not sure how patients will be treated: PTCA, CABG, medical therapyCABG, medical therapy
• Use of LMWHUse of LMWH
• Not sure Not sure whomwhom to treat or to treat or whenwhen to treat to treat
0
5
10
15
20
25
30
35Heparin Tirofiban + Heparin
Medical Rx PTCA CABG
16.814.8
24.2
18
33.2
28.7RR=13%
RR=32%
RR=20%
GP IIb/IIIa Inhibition: GP IIb/IIIa Inhibition: Composite Endpoint at 30 Days by Treatment Composite Endpoint at 30 Days by Treatment
Strategy in PRISM-PLUS*Strategy in PRISM-PLUS*
* Post-randomization analysis. Data available on File DA-AGG06(2)
0
5
10
15
20Heparin Tirofiban + Heparin
Medical Rx PTCA CABG
10.1
7.8
13.1
8.8
16.8
12.2
RR=25%RR=25%
RR=34%RR=34%
RR=30%RR=30%
GP IIb/IIIa Inhibition: GP IIb/IIIa Inhibition: Death or MI at 30 Days by Treatment Strategy Death or MI at 30 Days by Treatment Strategy
in PRISM-PLUS*in PRISM-PLUS*
* Post-randomization analysis. Data available on File DA-AGG06(2)
Current Limitations to the Use of Current Limitations to the Use of GP IIb/IIIa Inhibitors GP IIb/IIIa Inhibitors
• Physician perceptionsPhysician perceptions
– No incremental benefit beyond ASA-heparinNo incremental benefit beyond ASA-heparin
– Bleeding risk is unacceptableBleeding risk is unacceptable
• Not sure how patients will be treated: PTCA, Not sure how patients will be treated: PTCA, CABG, medical therapyCABG, medical therapy
• Use of LMWHUse of LMWH
• Not sure Not sure whomwhom to treat or to treat or whenwhen to treat to treat
Inclusion CriteriaInclusion Criteria
– Anginal pain at rest during previous 24 hours andAnginal pain at rest during previous 24 hours and
– New ST-T wave changes orNew ST-T wave changes or
– previous MI or revascularization orprevious MI or revascularization or
– results of invasive or non-invasive testing suggesting ischemic heart results of invasive or non-invasive testing suggesting ischemic heart diseasedisease
Selected Exclusion CriteriaSelected Exclusion Criteria
– Contraindications to anticoagulationContraindications to anticoagulation
– Persistent ST-elevationPersistent ST-elevation
Study DesignStudy Design
– Patients randomized to enoxaparin or unfractionated heparin for 2–8 Patients randomized to enoxaparin or unfractionated heparin for 2–8 days.days.
Entry Criteria, Exclusion Criteria and Study Entry Criteria, Exclusion Criteria and Study Design: ESSENCEDesign: ESSENCE
Cohen M et al. Cohen M et al. N Engl J MedN Engl J Med. 1997;337:447–452.. 1997;337:447–452.
1 2 14 30
% o
f P
atie
nts
Wit
h E
ven
ts%
of
Pat
ien
ts W
ith
Eve
nts
Days From RandomizationDays From Randomization
P = 0.019 P = 0.01623.3%
19.8%
Heparin, N=1564Enoxaparin, N=1607
15%
Adapted from Cohen M, et al. Adapted from Cohen M, et al. N Engl J MedN Engl J Med. 1997;337:447–452.. 1997;337:447–452.
0.30
0.25
0.20
0.15
0.10
0.05
0.00
ESSENCE: Enoxaparin in UA/NQWMIESSENCE: Enoxaparin in UA/NQWMICumulative Events at 14 Days:Cumulative Events at 14 Days:Death, MI, Recurrent AnginaDeath, MI, Recurrent Angina
19.8%
16.6%
Primary Endpoint
6.2%
7.4%P = 0.18
Treating Acute Coronary Treating Acute Coronary Syndrome Prior to Syndrome Prior to CatheterizationCatheterization
Current Limitations to the Use of Current Limitations to the Use of GP IIb/IIIa Inhibitors GP IIb/IIIa Inhibitors
• Physician perceptionsPhysician perceptions
– No incremental benefit beyond ASA-heparinNo incremental benefit beyond ASA-heparin
– Bleeding risk is unacceptableBleeding risk is unacceptable
• Not sure how patients will be treated: PTCA, Not sure how patients will be treated: PTCA, CABG, medical therapyCABG, medical therapy
• Use of LMWHUse of LMWH
• Not sureNot sure whomwhom to treat to treat or or whenwhen to treat to treat
Ischemic Chest Pain Ischemic Chest Pain Non–ST-Elevation ACSNon–ST-Elevation ACS
• Heparin and aspirinHeparin and aspirin• Glycoprotein IIb/IIIa inhibitorGlycoprotein IIb/IIIa inhibitor • NitratesNitrates• -Blocker-Blocker
Positive MarkersPositive Markers
ST Depression ST Depression 1mm 1mm
Dynamic ECG Dynamic ECG
or
or
PRISM-PLUS: Consistency of PRISM-PLUS: Consistency of Risk ReductionsRisk Reductions
The PRISM-PLUS Study Investigators. The PRISM-PLUS Study Investigators. N Engl J MedN Engl J Med. 1998;338:1488–1497.. 1998;338:1488–1497.
Age (y)
65 804 12.4% 8.5% 36%
65 766 23.5% 17.8% 30%
Gender
Female 506 19.0% 13.4% 33%
Male 1054 17.4% 12.7% 32%
AGGRASTATAGGRASTAT (tirofiban HCI) (tirofiban HCI) RiskRisknn HeparinHeparin + Heparin+ Heparin ReductionReduction
Prognostic Value of ECG Changes: GUSTO IIbPrognostic Value of ECG Changes: GUSTO IIb
Days From Randomization
Mo
rtal
ity,
%ST-Segment Elevation and DepressionST-Segment DepressionST-Segment ElevationIsolated T-Wave Inversion
Adapted from Savonitto S, et al. Adapted from Savonitto S, et al. JAMAJAMA. 1999;281:707-713.. 1999;281:707-713.
10
9
8
7
6
5
4
3
2
1
0 20 40 60 80 100 120 140 160 180
P 0.001
Conclusion: TnI has important prognostic value for patients with unstable angina
Adapted from Galvani M, et al. Adapted from Galvani M, et al. CirculationCirculation. 1997; 95:2053–2059.. 1997; 95:2053–2059.
5.8%
27.3%
0
5
10
15
20
25
P=0.02
Co
mp
osi
te E
nd
po
int
(30
day
s -
MI,
Dea
th)
TnI-n = 69
TnI+n = 22
Cardiac Endpoints in Unstable AnginaCardiac Endpoints in Unstable AnginaTroponin I in CK-MB Negative Patients with ECG Troponin I in CK-MB Negative Patients with ECG
ChangesChanges
30
Adapted from Armstrong PW, et al. Adapted from Armstrong PW, et al. Circulation.Circulation. 1998;98:1860–1868. 1998;98:1860–1868.
Prognostic Value of Refractory Ischemia Prognostic Value of Refractory Ischemia in Patients Without ST-Segment Elevation: GUSTO IIbin Patients Without ST-Segment Elevation: GUSTO IIb
Cumulative SurvivalCumulative Survival30-Day Infarction 30-Day Infarction
0
5
10
15
20
25
30
2.6%2.6%
9.2%9.2%
25.4%25.4%
%
1.00
DaysDays
.95
.90
.85
.80
.75
.70
60 120 180 240 300 3600
No Recurrent IschemiaNo Recurrent Ischemia Nonrefractory IschemiaNonrefractory Ischemia
Refractory IschemiaRefractory Ischemia
P<0.02
P<0.02
Current Limitations to the Use of Current Limitations to the Use of GP IIb/IIIa Inhibitors GP IIb/IIIa Inhibitors
• Physician perceptionsPhysician perceptions
– No incremental benefit beyond ASA-heparinNo incremental benefit beyond ASA-heparin
– Bleeding risk is unacceptableBleeding risk is unacceptable
• Not sure how patients will be treated: PTCA, Not sure how patients will be treated: PTCA, CABG, medical therapyCABG, medical therapy
• Use of LMWHUse of LMWH
• Not sure Not sure whomwhom to treat or to treat or whenwhen to treat to treat
0.030
0.025
0.020
0.015
0.010
0.005
0.000
6 300 12 18 24 36 42 48
Heparin only
AGGRASTAT® (tirofiban HCl) + Heparin
RR = 66%
All 1570 Patients Evaluated
Hours
Pro
bab
ilit
y o
f D
eath
o
r M
I
The PRISM-PLUS Study Investigators. The PRISM-PLUS Study Investigators. N Engl J MedN Engl J Med. 1998;338:1488–1497.. 1998;338:1488–1497.
PRISM-PLUS: Combined MI and Death PRISM-PLUS: Combined MI and Death During Initial 48 Hours in All PatientsDuring Initial 48 Hours in All Patients
Thrombus (N=643)
No Thrombus (N=784)
% P
atie
nts
Wit
h E
ven
t%
Pat
ien
ts W
ith
Eve
nt
0
5
15
10
20
Composite Refr. Ischemia MI DeathMI/Death
2%
20%*
10%
4%
12%*
6%
9%* 9%*
5%*5%
Events at 30 DaysEvents at 30 Days
* * PP<0.005<0.005..Adapted from Zhao XQ, et al. Adapted from Zhao XQ, et al. CirculationCirculation. 1999;100:1609–1615.. 1999;100:1609–1615.
Intracoronary Thrombus as a Predictor of Clinical Intracoronary Thrombus as a Predictor of Clinical Outcomes in Unstable Angina/NQWMIOutcomes in Unstable Angina/NQWMI
Recent Occlusion
PRISM-PLUS: Thrombus GradePRISM-PLUS: Thrombus Grade
Adapted from Zhao XQ, et al. Adapted from Zhao XQ, et al. CirculationCirculation. 1999;100:1609–1615.. 1999;100:1609–1615.
0
10
20
30
40
50
Cu
mu
lativ
e %
Cu
mu
lativ
e %
Heparin(n=622)
LargeRecent Occlusion
Tirofiban + Heparin(n=608)
Possible
Small
Moderate
Possible
Small
Moderate
OverallOdds Ratio:
0.77P=0.022
17.1%24.1%
Large
TIMI Flow as a Predictor of Clinical Outcomes in UAP/NQWMI
0
5
10
15
20
25
30 TIMI 0-2 (n=298) TIMI 3 (n=1095)
% P
atie
nts
Wit
h E
ven
t
20%
12%
5%
9%
Composite Refr. Ischemia MIMI/Death
6%10%
7.4% 5.5%
Events at 30 Days
Adapted from Zhao XQ, et al. Adapted from Zhao XQ, et al. CirculationCirculation. 1999;100:1609–1615.. 1999;100:1609–1615.
PRISM-PLUS: TIMI FlowPRISM-PLUS: TIMI Flow
Adapted from Zhao XQ, et al. Adapted from Zhao XQ, et al. CirculationCirculation. 1999;100:1609–1615.. 1999;100:1609–1615.
0
5
10
15
20
25
Cu
mu
lativ
e %
Cu
mu
lativ
e %
MinimalPerfusion(TIMI 1)
Heparin(n=580)
Totalocclusion
(TIMI 0)
Partialperfusion(TIMI 2)
Totalocclusion
(TIMI 0)
Partialperfusion(TIMI 2)
OverallOverallOdds Ratio:Odds Ratio:
0.650.65
PP=0.002=0.00218.1%
25.5%
Tirofiban + Heparin(n=570)
Acute Coronary Syndrome SummaryAcute Coronary Syndrome Summary
• Major adverse cardiac event rates are substantial despite therapy with aspirin and heparin.
• Studies show that therapy with GP IIb/IIIa inhibitors in combination with aspirin and heparin reduce the risk of adverse outcomes
– In patients with objective evidence of ischemia (ST depression, positive markers, dynamic ECG changes)
• GP IIb/IIIa inhibitors have an acceptable safety profile.
• Currently only 7% of ACS patients eligible for GP IIb/IIIa therapy are being treated.
Before prescribing AGGRASTAT® (tirofiban HCl), please read the complete Prescribing Information available at this presentation.
AGGRASTAT is a registered trademark of Merck & Co., Inc.© 2000 Merck & Co., Inc. All rights reserved. 003235(1)-05-AGG