the additive value of tirofiban administered with

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


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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


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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))


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PCI IndicationsPCI Indications

55%33%

10% 2%

ACS

SA

Silent Ischemia

Viability


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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%


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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


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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



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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 (%)



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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



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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



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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



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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



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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



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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.


the additive value of tirofiban administered with

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