Transcript The Additive Value of Tirofiban Administered With the High-Dose Bolus in the Prevention of Ischemic Complications During High-Risk Coronary Angioplasty The ADVANCE Trial M.

The Additive Value of Tirofiban Administered With
the High-Dose Bolus in the Prevention of Ischemic
Complications During High-Risk Coronary Angioplasty
The ADVANCE Trial
M. Valgimigli
Department of
Cardiology
University of Ferrara
University of Ferrara
Italy
Erasmus MC, Thoraxcenter
The Netherlands
30-day composite events (death,
MI, urgent TVR) by clinical status
9,0
8,0
7,0
6,0
5,0
4,0
p = 0.032
Tirofiban
8,5 p = 0.002
Abciximab
7,59
6,01
5,8
p = 0.32
5,6
4,5
3,0
2,0
1,0
0,0
all pts
acs pts
non acs pts
Dr Schneider’s Hypothesis
Baseline platelet reactivity is
not uniform in patients
undergoing PCI
The higher the baseline value,
the worse the outcome
Baseline platelet reactivity is
proportional to the clinical
status, lower in elective pts,
higher in NSTEACS and highest
in STEMI pts
Tirofiban, at Restore regimen,
is just enough, soon after the
bolus, to control platelet
reactivity in 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
AIM
To re-assess the efficacy of
Tirofiban when given at SHDB
on top of ADP receptor
blockers in:
I.
II.
Elective patients
NSTE-ACS patients
Department of Cardiology, University of Ferrara, Italy
AIM
To re-assess the efficacy of
Tirofiban when given at SHDB
on top of ADP receptor
blockers in High-Risk:
I.
Elective patients
i.
ii.
II.
Multivessel treatment
Diabetes
NSTE-ACS patients
i.
High-risk features (ESC guidelines)
Department of Cardiology, University of Ferrara, Italy
PCI Indications
Silent Ischemia
ACS
Viability
SA
10%
33%
2%
55%
Department of Cardiology, University of Ferrara, Italy
NSTE-ACS Population (n=111)
79%
Non High-risk
High-risk
73% Troponin positive
55% ST >0.5 mm 2 leads
23% Diabetes
Department of Cardiology, University of Ferrara, Italy
Study Protocol
160-325mg ASA
500mg ticlidopine bolus + 250mg bid
or
300mg clopidogrel bolus + 75mg daily
100U/kg bolus UFH +
Bolus to maintain 300s ACT
Placebo
50-70U/kg bolus UFH +
Bolus to maintain 200s ACT
25mcg/kg bolus tirofiban +
0.15mcg/kg/min infusion for 24-48 hours
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
Endpoints
Primary Endpoint
– Death, nonfatal MI,
TVR and thrombotic
bailout GP IIb/IIIa
≈199 Patients
30% events Controls
40% events reduction
β-error 0.8 α-error .05
Secondary Endpoints
– Each component of the
primary endpoint
– Effect of drug on troponin
I levels
– Effects in prespecified
subgroups
 Diabetics
 Patients with ACS
– TIMI major and minor
bleeding
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
Baseline Characteristics
Placebo
(n=101)
HDB Tirofiban
(n=101)
PValue
687
699
NS
Male sex (%)
66
69
NS
Diabetes (%)
45
53
NS
Heart failure (%)
15
19
NS
Previous PCI (%)
45
50
NS
Pervious MI (%)
21
19
NS
Creatinine (mg/dl)
1.10.3
1.00.2
NS
Characteristics
Age (yr)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
Baseline Characteristics
Placebo
(n=101)
HDB Tirofiban
(n=101)
PValue
687
699
NS
Male sex (%)
66
69
NS
Diabetes (%)
45
53
NS
Heart failure (%)
15
19
NS
Previous PCI (%)
45
50
NS
Pervious MI (%)
21
19
NS
Creatinine (mg/dl)
1.10.3
1.00.2
NS
Characteristics
Age (yr)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
Baseline Characteristics
Placebo
(n=101)
HDB Tirofiban
(n=101)
PValue
687
699
NS
Male sex (%)
66
69
NS
Diabetes (%)
45
53
NS
Heart failure (%)
15
19
NS
Previous PCI (%)
45
50
NS
Pervious MI (%)
21
19
NS
Creatinine (mg/dl)
1.10.3
1.00.2
NS
Characteristics
Age (yr)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
Baseline Characteristics
Placebo
(n=101)
HDB Tirofiban
(n=101)
PValue
687
699
NS
Male sex (%)
66
69
NS
Diabetes (%)
45
53
NS
Heart failure (%)
15
19
NS
Previous PCI (%)
45
50
NS
Pervious MI (%)
21
19
NS
Creatinine (mg/dl)
1.10.3
1.00.2
NS
Characteristics
Age (yr)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
Baseline Characteristics
Placebo
(n=101)
HDB Tirofiban
(n=101)
PValue
687
699
NS
Male sex (%)
66
69
NS
Diabetes (%)
45
53
NS
Heart failure (%)
15
19
NS
Previous PCI (%)
45
50
NS
Pervious MI (%)
21
19
NS
Creatinine (mg/dl)
1.10.3
1.00.2
NS
Characteristics
Age (yr)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
Baseline Characteristics
Placebo
(n=101)
HDB Tirofiban
(n=101)
PValue
687
699
NS
Male sex (%)
66
69
NS
Diabetes (%)
45
53
NS
Heart failure (%)
15
19
NS
Previous PCI (%)
45
50
NS
Pervious MI (%)
21
19
NS
Creatinine (mg/dl)
1.10.3
1.00.2
NS
Characteristics
Age (yr)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
Baseline Characteristics
Placebo
(n=101)
HDB Tirofiban
(n=101)
PValue
687
699
NS
Male sex (%)
66
69
NS
Diabetes (%)
45
53
NS
Heart failure (%)
15
19
NS
Previous PCI (%)
45
50
NS
Pervious MI (%)
21
19
NS
Creatinine (mg/dl)
1.10.3
1.00.2
NS
Characteristics
Age (yr)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
Baseline Characteristics
Placebo
(n=101)
HDB Tirofiban
(n=101)
PValue
687
699
NS
Male sex (%)
66
69
NS
Diabetes (%)
45
53
NS
Heart failure (%)
15
19
NS
Previous PCI (%)
45
50
NS
Pervious MI (%)
21
19
NS
Creatinine (mg/dl)
1.10.3
1.00.2
NS
Characteristics
Age (yr)
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
1° End-point
Suirvival Probability %
100
90
80
20%
70
35%
60
P=0,01
Tirofiban SHDB
Placebo
50
40
30
20
10
0
0
50
Valgimigli et al. (2004) JACC 44:14-19
100
150
200
250
300
350
400
Days
Department of Cardiology, University of Ferrara, Italy
Clinical Outcome
0.01
0.048
35
30
%
25
n.s.
20
Placebo
Tirofiban
0.052
15
10
n.s.
5
0
1°Endpoint
MACE
Death
MI
TVR
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
Troponin I and CK-MB
P<0. 01
14
12
ng/ml
10
P=0.001
8
Placebo
Tirofiban
6
4
2
0
Baseline
Post-PCI
Troponin I
Baseline
Post-PCI
CK-MB
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
Subgroup Analysis
Acute Coronary Syndrome
Yes
No
Diabetes
Yes
No
0.2
0.4
0.6
0.8
Tirofiban Better
1.0
1.2
1.4
1.6
1.8
Placebo Better
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
# Patients
Safety Results
20
18
16
14
12
10
8
6
4
2
0
Placebo
Tirofiban
P=0.19
No incidence of
major bleeding
No RBC transfusions
No severe
thrombocytopenia
One mild
thrombocytopenia in
each group
Minor Bleeding
Valgimigli et al. (2004) JACC 44:14-19
Department of Cardiology, University of Ferrara, Italy
CONCLUSIONS
Tirofiban when given at SHDB, immediately before
high-risk PCIs, to patients who have been pre-treated
with thienopyridines was:
• As safe as
• More 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
Department of Cardiology, University of Ferrara, Italy