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Department of Cardiology University of Ferrara. M. Valgimigli University of Ferrara Italy Erasmus MC, Thoraxcenter The Netherlands. The Additive Value of Tirofiban Administered With the High-Dose Bolus in the Prevention of Ischemic Complications During High-Risk Coronary Angioplasty - PowerPoint PPT Presentation
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The Additive Value of Tirofiban Administered Withthe High-Dose Bolus in the Prevention of Ischemic
Complications During High-Risk Coronary AngioplastyThe ADVANCE Trial
The Additive Value of Tirofiban Administered Withthe High-Dose Bolus in the Prevention of Ischemic
Complications During High-Risk Coronary AngioplastyThe ADVANCE Trial
M. Valgimigli
University of FerraraItaly
Erasmus MC, ThoraxcenterThe Netherlands
Department of Cardiology
University of Ferrara
7,59
6,01
0,0
1,0
2,0
3,0
4,0
5,0
6,0
7,0
8,0
9,0
all pts
30-day composite events 30-day composite events (death, MI, urgent TVR)(death, MI, urgent TVR)
p = 0.032 8,5
5,8
acs pts
p = 0.002
5,6
4,5
non acs pts
p = 0.32
Tirofiban
Abciximab
by by clinical statusclinical status
Department of Cardiology, University of Ferrara,
Italy
Dr Schneider’sDr Schneider’s Hypothesis HypothesisBaseline platelet reactivity Baseline platelet reactivity is not uniform in patients is not uniform in patients undergoing PCIundergoing PCI
The higher the baseline The higher the baseline value, the worse the value, the worse the outcomeoutcome
Baseline platelet reactivity Baseline platelet reactivity is proportional to the clinical is proportional to the clinical status, lower in elective pts, status, lower in elective pts, higher in NSTEACS and higher in NSTEACS and highest in STEMI ptshighest in STEMI ptsTirofiban, at Restore Tirofiban, at Restore regimen, is just enough, regimen, is just enough, soon aftersoon after the bolus, to the bolus, to control platelet reactivity in control platelet reactivity in elective patients elective patients
Circ 01; 104: 18; AJC 02; 90: 1421; AJC 03; 91: 334; AJC 03; 91: 872; Frossard Circ 04; 110
Department of Cardiology, University of Ferrara,
Italy
AIMAIM
To re-assess the efficacy of To re-assess the efficacy of Tirofiban when given at Tirofiban when given at SHDB on top of ADP SHDB on top of ADP receptor blockers in:receptor blockers in:
I.I. Elective patientsElective patients
II.II. NSTE-ACS patientsNSTE-ACS patients
Department of Cardiology, University of Ferrara,
Italy
AIMAIM
To re-assess the efficacy of To re-assess the efficacy of Tirofiban when given at Tirofiban when given at SHDB on top of ADP SHDB on top of ADP receptor blockers in receptor blockers in High-Risk::
I.I. Elective patientsElective patientsi.i. Multivessel treatmentMultivessel treatment
ii.ii. DiabetesDiabetes
II.II. NSTE-ACS patientsNSTE-ACS patientsi.i. High-risk features (High-risk features (ESC guidelinesESC guidelines))
Department of Cardiology, University of Ferrara,
Italy
PCI IndicationsPCI Indications
55%33%
10% 2%
ACS
SA
Silent Ischemia
Viability
Department of Cardiology, University of Ferrara,
Italy
NSTE-ACS Population NSTE-ACS Population (n=111)(n=111)
Non High-risk
High-risk
73% Troponin positive55% ST >0.5 mm 2 leads23% Diabetes
79%
Department of Cardiology, University of Ferrara,
Italy
160-325mg ASA
100U/kg bolus UFH +Bolus to maintain 300s ACT
500mg ticlidopine bolus + 250mg bid or
300mg clopidogrel bolus + 75mg daily
50-70U/kg bolus UFH +Bolus to maintain 200s ACT
Placebo 25mcg/kg bolus tirofiban +0.15mcg/kg/min infusion for 24-48 hours
Valgimigli et al. (2004) JACC 44:14-19
Study Protocol
Department of Cardiology, University of Ferrara,
Italy
EndpointsEndpointsPrimary EndpointPrimary Endpoint– Death, nonfatal MI, Death, nonfatal MI,
TVR and thrombotic TVR and thrombotic bailout GP IIb/IIIabailout GP IIb/IIIa
Secondary EndpointsSecondary Endpoints– Each component of the Each component of the
primary endpointprimary endpoint– Effect of drug on Effect of drug on
troponin I levelstroponin I levels– Effects in prespecified Effects in prespecified
subgroupssubgroups DiabeticsDiabetics Patients with ACSPatients with ACS
– TIMI major and minor TIMI major and minor bleedingbleeding
≈199 Patients30% events Controls40% events reductionβ-error 0.8 α-error .05
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Baseline CharacteristicsBaseline Characteristics
CharacteristicsPlacebo(n=101)
HDB Tirofiban (n=101)
P-Value
Age (yr) 687 699 NS
Male sex (%) 66 69 NS
Diabetes (%) 45 53 NS
15 19 NS
Previous PCI (%) 45 50 NS
Pervious MI (%) 21 19 NS
Creatinine (mg/dl) 1.10.3 1.00.2 NS
Heart failure (%)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Baseline CharacteristicsBaseline Characteristics
CharacteristicsPlacebo(n=101)
HDB Tirofiban (n=101)
P-Value
Age (yr) 687 699 NS
Male sex (%) 66 69 NS
Diabetes (%) 45 53 NS
15 19 NS
Previous PCI (%) 45 50 NS
Pervious MI (%) 21 19 NS
Creatinine (mg/dl) 1.10.3 1.00.2 NS
Heart failure (%)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Baseline CharacteristicsBaseline Characteristics
CharacteristicsPlacebo(n=101)
HDB Tirofiban (n=101)
P-Value
Age (yr) 687 699 NS
Male sex (%) 66 69 NS
Diabetes (%) 45 53 NS
15 19 NS
Previous PCI (%) 45 50 NS
Pervious MI (%) 21 19 NS
Creatinine (mg/dl) 1.10.3 1.00.2 NS
Heart failure (%)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Baseline CharacteristicsBaseline Characteristics
CharacteristicsPlacebo(n=101)
HDB Tirofiban (n=101)
P-Value
Age (yr) 687 699 NS
Male sex (%) 66 69 NS
Diabetes (%) 45 53 NS
15 19 NS
Previous PCI (%) 45 50 NS
Pervious MI (%) 21 19 NS
Creatinine (mg/dl) 1.10.3 1.00.2 NS
Heart failure (%)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Baseline CharacteristicsBaseline Characteristics
CharacteristicsPlacebo(n=101)
HDB Tirofiban (n=101)
P-Value
Age (yr) 687 699 NS
Male sex (%) 66 69 NS
Diabetes (%) 45 53 NS
15 19 NS
Previous PCI (%) 45 50 NS
Pervious MI (%) 21 19 NS
Creatinine (mg/dl) 1.10.3 1.00.2 NS
Heart failure (%)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Baseline CharacteristicsBaseline Characteristics
CharacteristicsPlacebo(n=101)
HDB Tirofiban (n=101)
P-Value
Age (yr) 687 699 NS
Male sex (%) 66 69 NS
Diabetes (%) 45 53 NS
15 19 NS
Previous PCI (%) 45 50 NS
Pervious MI (%) 21 19 NS
Creatinine (mg/dl) 1.10.3 1.00.2 NS
Heart failure (%)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Baseline CharacteristicsBaseline Characteristics
CharacteristicsPlacebo(n=101)
HDB Tirofiban (n=101)
P-Value
Age (yr) 687 699 NS
Male sex (%) 66 69 NS
Diabetes (%) 45 53 NS
15 19 NS
Previous PCI (%) 45 50 NS
Pervious MI (%) 21 19 NS
Creatinine (mg/dl) 1.10.3 1.00.2 NS
Heart failure (%)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Baseline CharacteristicsBaseline Characteristics
CharacteristicsPlacebo(n=101)
HDB Tirofiban (n=101)
P-Value
Age (yr) 687 699 NS
Male sex (%) 66 69 NS
Diabetes (%) 45 53 NS
15 19 NS
Previous PCI (%) 45 50 NS
Pervious MI (%) 21 19 NS
Creatinine (mg/dl) 1.10.3 1.00.2 NS
Heart failure (%)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
1° End-point1° End-point
Su
irviv
al P
rob
ab
ilit
y %
20%
35% P=0,01
0 50 100 150 200 250 300 350 400
Days
0
10
20
30
40
50
60
70
80
90
100
Tirofiban SHDB Placebo
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Clinical OutcomeClinical Outcome
0
5
10
15
20
25
30
35
Placebo
Tirofiban
%
1°Endpoint MACE Death MI TVR
n.s.
n.s.
0.052
0.0480.01
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Troponin I and CK-MBTroponin I and CK-MB
0
2
4
6
8
10
12
14
Baseline Post-PCI Baseline Post-PCI
PlaceboTirofiban
P=0.001
P<0. 01
Troponin I CK-MB
ng/
ml
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Subgroup AnalysisSubgroup Analysis
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8
Tirofiban Better Placebo Better
Acute Coronary SyndromeYes
No
Diabetes
Yes
No
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
Safety ResultsSafety Results
No incidence of No incidence of major bleedingmajor bleeding
No RBC No RBC transfusionstransfusions
No severe No severe thrombocytopeniathrombocytopenia
One mild One mild thrombocytopenia thrombocytopenia in each groupin each groupMinor Bleeding
Placebo
Tirofiban
P=0.19
# P
atie
nts
0
2
4
6
8
10
12
14
16
18
20
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara,
Italy
CONCLUSIONSCONCLUSIONS
Tirofiban when given at SHDB, immediately before high-risk PCIs, to patients who have been pre-treated with thienopyridines was:
• As safe asAs safe as• More effective thanMore effective than
UFH alone in the prevention of periprocedural ischemic complications
Our current findings, based on a limited and selected sample size, should be viewed as preliminary, thus giving input for further research in this field.
Valgimigli et al. (2004) JACC 44:14-19