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Incidence of Acute Coronary Syndromes (ACS): Incidence of Acute Coronary Syndromes (ACS): Statistics From Various StudiesStatistics From Various Studies
• 1.4 million hospitalizations each year for ACS
• 944,000 hospitalizations for unstable angina; 1994
• 121,000 hospitalizations for non–Q-wave MI; 1994
60% patients with unstable angina >65 years old
• 46% of patients with unstable angina are women
Hochman JS et al. Hochman JS et al. J Am Coll CardiolJ Am Coll Cardiol. 1997;30:141-148; . 1997;30:141-148; Vital and Health StatisticsVital and Health Statistics. Hyattsville, Md: . Hyattsville, Md: 1994: Series 13, No. 127; 1994: Series 13, No. 127; Clinical Practice GuidelinesClinical Practice Guidelines. AHCPR publication No. 94-0602.. AHCPR publication No. 94-0602.
Clinical Trials of Unstable Angina and Clinical Trials of Unstable Angina and NQWMI: Short-Term MortalityNQWMI: Short-Term Mortality
The TIMI IIIB Investigators. The TIMI IIIB Investigators. Circulation.Circulation. 1994;89:1545-1556; Cohen M et al. 1994;89:1545-1556; Cohen M et al. J Am Coll Cardiol. J Am Coll Cardiol. 1993;32:1338-1343; Lindahl B et al. 1993;32:1338-1343; Lindahl B et al. Circulation. Circulation. 1996;93:1651-1657.1996;93:1651-1657.
0
2
4
6
8
10
12
TIMI IIIB FRISC ATACS1407 976 330
6 weeks 5 months 12 weeksN =F/U =
Unstable AnginaUnstable Angina
NQWMINQWMI
% M
orta
lity
Clinical Trials of Unstable Angina and Clinical Trials of Unstable Angina and NQWMI: Short-Term Risk of MINQWMI: Short-Term Risk of MI
The TIMI IIIB Investigators. The TIMI IIIB Investigators. Circulation.Circulation. 1994;89:1545-1556; Cohen M et al. 1994;89:1545-1556; Cohen M et al. J Am Coll Cardiol. J Am Coll Cardiol. 1993;32:1338-1343; FRISC Study Group. 1993;32:1338-1343; FRISC Study Group. Lancet. Lancet. 1996;347:561-568; Klein W et al. 1996;347:561-568; Klein W et al. CirculationCirculation. . 1997;96(1):61-68; Cohen M et al. 1997;96(1):61-68; Cohen M et al. N Engl J MedN Engl J Med. 1997;337:447-452.. 1997;337:447-452.
6.5%
4.0%
11.0%
5.5%
3.4%
8.1%
4.5%
0
2
4
6
8
10
12
TIMI IIIB ATACS ESSENCE FRISC FRIC
Unstable Angina Pectoris(UAP)
NQWMI
UAP+NQWMI
% In
cid
ence
MI
% In
cid
ence
MI
6 Weeks 12 Weeks 30 Days 40 Days 45 DaysF/U =
Ischemic Heart Disease: Ischemic Heart Disease: Time-Dependent Mortality RiskTime-Dependent Mortality Risk
0
5
10
15
20
25
0 1 2 3 4 5 6
De
ath
s/1
00
Pts
/Mon
thD
ea
ths/
10
0 P
ts/M
onth
Months After Hospital AdmissionMonths After Hospital Admission
Acute MIAcute MI
Unstable AnginaUnstable Angina
Stable AnginaStable Angina
Clinical Practice Guidelines.Clinical Practice Guidelines. AHCPR publication No. 94-0602. AHCPR publication No. 94-0602.
Determinants of Plaque VulnerabilityDeterminants of Plaque Vulnerability
Downstream Downstream embolizationembolization
DETERMINANTS OF DETERMINANTS OF THROMBOSIS THROMBOSIS - Local factors- Local factors- Systemic factors- Systemic factors
UNSTABLE CORONARYUNSTABLE CORONARY ARTERY DISEASEARTERY DISEASE
RecanalizationRecanalization
LysisLysis
Remodeling
Remodeling
DYNAMIC
Lysis/
Repair
Lysis/
Repair
Cap disruptionCap disruption- Vulnerability- Vulnerability- Triggers- Triggers
VULNERABLE PLAQUEVULNERABLE PLAQUE
Fibrous capFibrous cap
Inflammation and repairInflammation and repair
Core sizeCore size
Lipid-rich coreLipid-rich core
Thr
ombo
lysi
s Throm
bosis
Fibrous tissue
Atheromatous material(lipid-rich)
Thrombus
Plaque hemorrhage
Macrophage
Smooth muscle cell
Theroux P, Fuster V. Theroux P, Fuster V. CirculationCirculation. 1998;97:1195-1206.. 1998;97:1195-1206.
CapCapthicknessthickness
LumenLumen
AGGRASTATAGGRASTAT (tirofiban HCl): Profile (tirofiban HCl): Profile
• Nonpeptide tyrosine derivative with MW 495 kD• Short-acting, reversible intravenous agent
– Upon discontinuation of AGGRASTAT, platelet function returns to near baseline within 4-8 hours in 90% of patients
• Nonpeptide inhibitor of platelet GP IIb/IIIa receptor• Blocks fibrinogen binding, inhibits aggregation• High specificity for receptor
HN CH2CH2CH2CH2O
COOH
HNHSO2CH2CH2CH2CH3
CH2
C• HCI • H2O
AGGRASTAT Prescribing Information.AGGRASTAT Prescribing Information.
Indications for AGGRASTATIndications for AGGRASTAT®® (tirofiban HCl) (tirofiban HCl)
• AGGRASTAT, in combination with heparin, is indicated for the treatment of ACS, including patients who are to be managed medically and those undergoing PTCA or atherectomy. In this setting, AGGRASTAT has been shown to decrease the rate of a combined endpoint of death, new myocardial infarction or refractory ischemia/repeat cardiac procedure.
AGGRASTAT Prescribing Information.AGGRASTAT Prescribing Information.
Contraindications for Contraindications for AGGRASTATAGGRASTAT
®® (tirofiban HCl) (tirofiban HCl)
AGGRASTAT is contraindicated in patients with:
• Known hypersensitivity to any component of the product
• Active internal bleeding or a history of bleeding diathesis within the previous 30 days
• History of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm
• History of thrombocytopenia following prior exposure to AGGRASTAT
• History of stroke within 30 days or any history of hemorrhagic stroke
• Major surgical procedure or severe physical trauma within the previous month
• History, symptoms, or findings suggestive of aortic dissection
• Severe hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg)
• Concomitant use of another parenteral GP IIb/IIIa inhibitor
• Acute pericarditis
AGGRASTAT Prescribing Information.AGGRASTAT Prescribing Information.
PRISMPRISM
PRISM-PLUSPRISM-PLUS
MedicalStabilization
ContinuedMedical Therapy
Presentation
± Angiography
Clinical Program for AGGRASTATClinical Program for AGGRASTAT
®®(tirofiban HCl) (tirofiban HCl)
in UAP/NQWMIin UAP/NQWMI
The PRISM Study Investigators. The PRISM Study Investigators. N Engl J MedN Engl J Med. 1998;338:1498-1505.. 1998;338:1498-1505.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.The RESTORE Investigators. The RESTORE Investigators. CirculationCirculation. 1997;96:1445-1453.. 1997;96:1445-1453.
RESTORERESTORE
PTCA
CABG
PRISM-PLUS: Entry CriteriaPRISM-PLUS: Entry Criteria
• 1915 patients with UAP or NQWMI randomized
• Entry criteria– Prolonged anginal pain or repetitive episodes of angina
at rest or during minimal exercise in previous 12 h and– New transient or persistent ST-T ischemic changes on
the ECG or– Elevation of plasma CK and CK-MB– 1570 patients evaluated
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: Exclusion CriteriaPRISM-PLUS: Exclusion CriteriaPatients were excluded from the study if they had
• ST-segment elevation >20 min
• Thrombolysis in previous 48 h
• Coronary angioplasty within the previous 6 mo or bypass surgery within the previous 1 mo
• Angina caused by identifiable factors
• History of a platelet disorder or thrombocytopenia
• Active bleeding or a high risk of bleeding
• Stroke within the previous year
• Serum creatinine >2.5 mg/dL or platelets <150,000/mm3
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.
Angiography+ PTCA
Hour 0 96 108 Day 7
Study Drug
Day 30
Primary Primary EndpointEndpoint
Secondary Endpoint
Secondary Endpoint
Day 180
PrespecifiedLong-termFollow-up
Random-ization
48
PRISM-PLUS: Study DesignPRISM-PLUS: Study Design
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.
0
5
10
15
20
PRISM-PLUS: Event Reductions at 7 DaysPRISM-PLUS: Event Reductions at 7 Days
RR=32%RR=32%PP=0.004=0.004
Composite Endpoint
RefractoryIschemia
MI/Death
RR=30%RR=30%PP=0.02=0.02
RR=47%RR=47%PP=0.006=0.006
RR=43%RR=43%PP=0.006=0.006
MI
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.
PP=0.99=0.99
Death
% P
atie
nts
% P
atie
nts
Heparin (n=797)
AGGRASTAT® (tirofiban HCl) + Heparin (n=773)
PRISM-PLUS: Composite Endpoint PRISM-PLUS: Composite Endpoint at 2, 7, and 30 Daysat 2, 7, and 30 Days
0
5
10
15
20
25
PP=NS=NS
RR=32%RR=32%PP=0.004=0.004
RR=22%RR=22%PP=0.029=0.029
2 Days 7 Days 30 Days
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.
7.87.85.75.7
17.917.9
12.912.9
22.322.3
18.518.5
% P
atie
nts
% P
atie
nts
Heparin (n=797)
AGGRASTAT® (tirofiban HCl) + Heparin (n=773)
PRISM-PLUS: Combined MI/Death Event PRISM-PLUS: Combined MI/Death Event Reductions at 2, 7, and 30 DaysReductions at 2, 7, and 30 Days
RR=66%RR=66%PP=0.01=0.01
2 Days 7 Days
RR=43%RR=43%PP=0.006=0.006
RR=30%RR=30%PP=0.03=0.03
30 Days
2.62.60.90.9
8.38.3
4.94.9
11.911.9
8.78.7
% P
atie
nts
% P
atie
nts
The PRISM-PLUS Study Investigators. The PRISM-PLUS Study Investigators. N Engl J MedN Engl J Med. 1998;338:1488-1497.. 1998;338:1488-1497.
Heparin (n=797)
AGGRASTAT® (tirofiban HCl) + Heparin (n=773)
DayDay
PRISM-PLUS: Composite Endpoint (180 Days)PRISM-PLUS: Composite Endpoint (180 Days)
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.
5
10
15
20
25
% W
ith E
ndp
oin
t%
With
En
dpo
int
HeparinHeparin
AGGRASTATAGGRASTAT®® (tirofiban HCl) (tirofiban HCl)+ Heparin+ Heparin
= -5.0%, RR=32%, P=0.004
0 30 60 90 120 150 1807
= -3.8%, RR=22%, P=0.029
= -4.4%, RR=19%, P=0.02
30
35
Day
2
4
6
8
10
12
14
16
18
% W
ith E
ndp
oin
t%
With
En
dpo
int
HeparinHeparin
AGGRASTATAGGRASTAT®® (tirofiban HCl) (tirofiban HCl)+ Heparin+ Heparin
= -3.0%
P=0.06= -3.2%
P=0.03
=-3.4%, RR=43%, P=0.006
0 30 60 90 120 150 1807
RR=30%
RR=22%
PRISM-PLUS: Combined MI/Death (180 Days)PRISM-PLUS: Combined MI/Death (180 Days)
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.
0
5
10
15
PRISM-PLUS: Composite Endpoint at 30 Days in PRISM-PLUS: Composite Endpoint at 30 Days in Patients Treated MedicallyPatients Treated Medically
RR=13%RR=13%
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.
16.8%16.8%14.8%14.8%
% P
atie
nts
% P
atie
nts
Heparin (n=375)
AGGRASTAT® (tirofiban HCl) + Heparin (n=344)
10
20
0
5
10
15
PRISM-PLUS: Combined MI/Death Outcomes PRISM-PLUS: Combined MI/Death Outcomes at 30 Days in Patients Treated Medicallyat 30 Days in Patients Treated Medically
RR=25%RR=25%
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.
10.1%10.1%
7.8%7.8%
% P
atie
nts
% P
atie
nts
Heparin (n=375)
AGGRASTAT® (tirofiban HCl) + Heparin (n=344)
Heparin (n=236)
AGGRASTAT® (tirofiban HCl) + Heparin (n=239)
PRISM-PLUS: Composite EndpointPRISM-PLUS: Composite Endpoint at 30 Days at 30 Days Among Patients Undergoing PTCAAmong Patients Undergoing PTCA
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.
0
5
10
15
RR=32%RR=32%
24.2%24.2%
18.0%18.0%%
Pa
tien
ts%
Pa
tien
ts20
25
0
5
10
15
Heparin (n=236)
AGGRASTAT® (tirofiban HCI) + Heparin (n=239)
PRISM-PLUS: Combined MI/Death Outcomes PRISM-PLUS: Combined MI/Death Outcomes at 30 Days Among Patients Undergoing at 30 Days Among Patients Undergoing PTCAPTCA
RR=34%RR=34%
13.1%13.1%
8.8%8.8%
% P
atie
nts
% P
atie
nts
The PRISM-PLUS Study Investigators. The PRISM-PLUS Study Investigators. N Engl J MedN Engl J Med. 1998;338:1488-1497.. 1998;338:1488-1497.
PRISM-PLUS: Composite Endpoint Following PTCAPRISM-PLUS: Composite Endpoint Following PTCA
= -6.2%
0 30 60 90 120 150 180Day
4
8
12
16
20
24
28
32
% W
ith E
ndp
oin
t%
With
En
dpo
int HeparinHeparin
AGGRASTATAGGRASTAT®® (tirofiban HCl) (tirofiban HCl)+ Heparin+ Heparin
= -6.5%RR=45%
RR=27%
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. DA-AGG08. Available on request from Merck & Co., Inc.DA-AGG08. Available on request from Merck & Co., Inc.
PRISM-PLUS: Composite Endpoint at 30 Days Among PRISM-PLUS: Composite Endpoint at 30 Days Among Patients Who Underwent CABG Subsequent to Patients Who Underwent CABG Subsequent to Treatment With AGGRASTATTreatment With AGGRASTAT
®® (tirofiban HCl) (tirofiban HCl)
DA-AGG06. Available on request from Merck & Co., Inc.DA-AGG06. Available on request from Merck & Co., Inc.
Heparin (n=184)AGGRASTAT+ Heparin (n=181)
0
RR=20%RR=20%
33.2%33.2%
28.7%28.7%%
Pat
ient
s%
Pat
ient
s
5
10
15
20
25
30
35
PRISM-PLUS: Combined MI/Death Outcomes at 30 Days PRISM-PLUS: Combined MI/Death Outcomes at 30 Days Among Patients Who Underwent CABG Subsequent to Among Patients Who Underwent CABG Subsequent to
Treatment With AGGRASTATTreatment With AGGRASTAT ®® (tirofiban HCl) (tirofiban HCl)
DA-AGG06. Available on request from Merck & Co., Inc.DA-AGG06. Available on request from Merck & Co., Inc.
Heparin (n=184)
AGGRASTAT + Heparin (n=181)
RR=30%RR=30%
16.8%16.8%
12.2%12.2%%
Pat
ient
s%
Pat
ient
s
0
5
10
15
20
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: Consistency of Risk ReductionsPRISM-PLUS: Consistency of Risk Reductions
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%
nn HeparinHeparinAGGRASTATAGGRASTAT®® (tirofiban HCl) (tirofiban HCl)
+ Heparin+ HeparinRisk Risk
ReductionReduction
Percent of Patients Experiencing Composite Endpoint at 7 DaysPercent of Patients Experiencing Composite Endpoint at 7 Days
PRISM-PLUS: Combined MI and Death During PRISM-PLUS: Combined MI and Death During Initial 48 Hours in All Patients and Postprocedure Initial 48 Hours in All Patients and Postprocedure in Patients Undergoing PTCAin Patients Undergoing PTCA
2 4 14 21 287
0.12
0.08
0.04
0.00
Heparin onlyHeparin only
RR = 44%RR = 44%
475 Patients Undergoing PTCA475 Patients Undergoing PTCA
0.030
0.025
0.020
0.015
0.010
0.005
0.000
6 300 12 18 24 36 42 48
Heparin onlyHeparin only
AGGRASTATAGGRASTAT®® (tirofiban HCl) (tirofiban HCl) + Heparin+ Heparin
RR = 66%RR = 66%
All 1570 Patients EvaluatedAll 1570 Patients Evaluated
HoursHours DaysDays
Drug InfusionDrug InfusionPTCAPTCA
Pro
babi
lity
of D
eath
or
MI
Pro
babi
lity
of D
eath
or
MI
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.
AGGRASTATAGGRASTAT®® (tirofiban HCl) (tirofiban HCl) + Heparin+ Heparin
Major Bleeding (TIMI)Intracranial bleeding
Minor Bleeding (TIMI)
Transfusions (All blood products)
Platelets 90,000/mm3
1.4%0.0%
10.5%
4.0%
1.9%
0.8%0.0%
8.0%
2.8%
0.8%
AGGRASTATAGGRASTAT ®®
(tirofiban HCl) + Heparin(tirofiban HCl) + Heparinn=773n=773
HeparinHeparinn=797n=797
PRISM-PLUS: Hematologic ComplicationsPRISM-PLUS: Hematologic Complications
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 %%
AGGRASTATAGGRASTAT ®® (tirofiban HCl) (tirofiban HCl)
+ Heparin+ Heparin HeparinHeparin
PRISM-PLUS: Incidence of TIMI Major Bleeding in PRISM-PLUS: Incidence of TIMI Major Bleeding in Patients Undergoing Interventional ProceduresPatients Undergoing Interventional Procedures
AGGRASTAT Prescribing Information.AGGRASTAT Prescribing Information.
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: Angiographic SubstudyPRISM-PLUS: Angiographic Substudy
• Objective: Effect of AGGRASTAT® (tirofiban HCl) on angiographically apparent thrombus
• Films prior to hour 97 analyzed by blinded Core Laboratory
• 1230 films readable and analyzed (608 in AGGRASTAT + heparin group; 622 in heparin group)
DA-AGG11. Available on request from Merck & Co., Inc.DA-AGG11. Available on request from Merck & Co., Inc.
PRISM-PLUS: Thrombus GradePRISM-PLUS: Thrombus Grade
DA-AGG11. Available on request from Merck & Co., Inc.DA-AGG11. Available on request from Merck & Co., Inc.
0
10
20
30
40
50C
um
ula
tive
%C
um
ula
tive
%
Heparin(n=622)
LargeRecent Occlusion
AGGRASTAT® (tirofiban HCl) + Heparin(n=608)
Possible
Small
Moderate
Possible
Small
Moderate
OverallOdds Ratio:
0.77P=0.022
17.1%24.1%
LargeRecent Occlusion
PRISM-PLUS: TIMI FlowPRISM-PLUS: TIMI Flow
DA-AGG11. Available on request from Merck & Co., Inc.DA-AGG11. Available on request from Merck & Co., Inc.
0
5
10
15
20
25
Cu
mu
lativ
e %
Cu
mu
lativ
e %
MinimalPerfusion(TIMI 1)
AGGRASTAT® (tirofiban HCl) + Heparin(n=570)
Heparin(n=580)
TotalOcclusion
(TIMI 0)
PartialPerfusion(TIMI 2)
TotalOcclusion
(TIMI 0)
PartialPerfusion(TIMI 2)
OverallOdds Ratio:
0.65P=0.00218.1%
25.5%
RESTORE: Inclusion and Exclusion CriteriaRESTORE: Inclusion and Exclusion Criteria
The RESTORE Investigators. The RESTORE Investigators. CirculationCirculation. 1997;96:1445-1453.. 1997;96:1445-1453.
• Acute coronary syndrome within 72 hours– MI (Q-wave and NQWMI)– UAP
• Documentation– ECG ischemia or– CK elevation or– Angiographic thrombus
Inclusion Criteria
• Thrombolytic therapy within 24 hours• Contraindication to anticoagulation• History of platelet disorder or thrombocytopenia• History of stroke or other intracranial pathology predisposing to bleeding• Scheduled for elective stent placement or angioplasty using a rotablator or
transluminal extraction catheter device
Exclusion Criteria
Study Drug(10 g/kg bolus/0.15 g/kg/min infusion)
Prespecified Analyses
Hour 0 36 Day 2 Day 7 Day 30 Day 180
Primary Primary EndpointEndpoint
Secondary Endpoint
Randomization at Angioplasty/Atherectomy
RESTORE: Study DesignRESTORE: Study Design
The RESTORE Investigators. The RESTORE Investigators. CirculationCirculation. 1997;96:1445-1453.. 1997;96:1445-1453.
RR=17%
RESTORE: Composite EndpointRESTORE: Composite Endpoint
The RESTORE Investigators. The RESTORE Investigators. CirculationCirculation. 1997;96:1445-1453.. 1997;96:1445-1453.
0 5 10 15 20 25 30Day
0
3
6
9
12 Placebo + HeparinPlacebo + Heparin
AGGRASTATAGGRASTAT®® (tirofiban HCl) (tirofiban HCl) + Heparin+ Heparin
=-3.3%
=-1.9%
=-2.8% P=0.17
P=0.023
P=0.004RR=38%
RR=28%
% W
ith C
om
po
site
En
dpo
int
% W
ith C
om
po
site
En
dpo
int
Major Bleeding (TIMI) Intracranial bleeding
Minor Bleeding (TIMI)
Transfusions (All blood products)
Platelets 90,000/mm3
Patients Undergoing CABGPatients Undergoing CABG
Major Bleeding (TIMI)
2.2%0.1%
12.0%
4.3%
1.1%
n=12n=12
25.0%
1.6%0.3%
6.3%
2.5%
0.9%
n=16n=16
37.5%
AGGRASTATAGGRASTAT ® ® (tirofiban HCl) (tirofiban HCl)
+ Heparin+ Heparinn=1071n=1071
HeparinHeparinn=1070n=1070
RESTORE: Hematologic ComplicationsRESTORE: Hematologic Complications
AGGRASTAT Prescribing Information.AGGRASTAT Prescribing Information.The RESTORE Investigators. The RESTORE Investigators. CirculationCirculation. 1997;96:1445-1453.. 1997;96:1445-1453.
All PatientsAll Patients
AGGRASTATAGGRASTAT®® (tirofiban HCl) (tirofiban HCl) Data SummaryData Summary
• Reversible, nonpeptide GP IIb/IIIa platelet receptor blocker
• Fast-on and fast-off antiplatelet effects
• Upon discontinuation of AGGRASTAT, platelet function returns to near baseline within 4-8 hours in 90% of patients
• Sustained clinical benefits (7, 30, and 180 days)
• Patients benefited regardless of treatment strategy (medical management, PTCA or CABG)
• Benefits were consistent regardless of patient’s age or gender
• Bleeding is the most common complication encountered during therapy with AGGRASTAT
AGGRASTAT Prescribing Information.AGGRASTAT Prescribing Information.