Stent Parameters Predict Major Adverse Stent Parameters Predict Major Adverse Clinical Events and the Response to Clinical Events and the Response to

Platelet Glycoprotein IIb/IIIa BlockadePlatelet Glycoprotein IIb/IIIa BlockadeFindings of the ESPRIT TrialFindings of the ESPRIT Trial

Stent Parameters Predict Major Adverse Stent Parameters Predict Major Adverse Clinical Events and the Response to Clinical Events and the Response to

Platelet Glycoprotein IIb/IIIa BlockadePlatelet Glycoprotein IIb/IIIa BlockadeFindings of the ESPRIT TrialFindings of the ESPRIT Trial

James E. Tcheng, MD; Ing Haan Lim, MBBS; Shankar Srinivasan, PhD; Joseph Jozic, MD; C. Michael Gibson, MS, MD; J. Conor O’Shea, MD;

Joseph A. Puma, MD; Daniel I. Simon, MD

Circulation Cardiovascular Interventions. 2009;2:43-51

Stent Parameters and MACE

Post-hoc analysis of the 1983 pts in ESPRIT receiving a stent

MACE (48 hr, 1 yr) by nominal stent parameters Number of stents implanted (1, 2, >3) Total length of stent (quartiles of mm) Stent diameter (<2.5, >2.5-<3.5, >3.5 mm) Stented vessel area (quartiles of mm2)

Analysis by randomization Placebo versus eptifibatide

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

eptifibatideeptifibatide180+180 µg/kg bolus180+180 µg/kg bolus

(boluses 10 min apart)(boluses 10 min apart)2.0 µg/kg-min infusion x18-24°2.0 µg/kg-min infusion x18-24°

++heparinheparin 60 U/kg bolus60 U/kg bolus

(ACT 200-300 sec)(ACT 200-300 sec)

eptifibatideeptifibatide180+180 µg/kg bolus180+180 µg/kg bolus

(boluses 10 min apart)(boluses 10 min apart)2.0 µg/kg-min infusion x18-24°2.0 µg/kg-min infusion x18-24°

++heparinheparin 60 U/kg bolus60 U/kg bolus

(ACT 200-300 sec)(ACT 200-300 sec)

placeboplacebo(bailout permitted)(bailout permitted)

++

heparinheparin 60 U/kg bolus60 U/kg bolus(ACT 200-300 sec)(ACT 200-300 sec)

placeboplacebo(bailout permitted)(bailout permitted)

++

heparinheparin 60 U/kg bolus60 U/kg bolus(ACT 200-300 sec)(ACT 200-300 sec)

vs.vs.vs.vs.

Study DesignStudy DesignStudy DesignStudy Design

ASA, thienopyridine pre-rx; randomization in cath labASA, thienopyridine pre-rx; randomization in cath labASA, thienopyridine pre-rx; randomization in cath labASA, thienopyridine pre-rx; randomization in cath lab

elective (non-urgent) stent PCIelective (non-urgent) stent PCI48 hour, 30 day, 6 month, 1 year follow-up48 hour, 30 day, 6 month, 1 year follow-up

primary endpoint: 48° death, MI, urg revasc, thrombotic bailoutprimary endpoint: 48° death, MI, urg revasc, thrombotic bailout

elective (non-urgent) stent PCIelective (non-urgent) stent PCI48 hour, 30 day, 6 month, 1 year follow-up48 hour, 30 day, 6 month, 1 year follow-up

primary endpoint: 48° death, MI, urg revasc, thrombotic bailoutprimary endpoint: 48° death, MI, urg revasc, thrombotic bailout

1999-2000

O’Shea JC et al., Am Heart J. 2000;140:834–839

10.5%

9.0%

4.9%

1.0%2.1%

0.2%

6.6%5.4%

3.3%

0.6% 1.0%0.1%

0%

5%

10%

15%

primaryendpt

MI large MI urgent TVR thromboticbailout

death

placebo

eptifibatide

10.5%

9.0%

4.9%

1.0%2.1%

0.2%

6.6%5.4%

3.3%

0.6% 1.0%0.1%

0%

5%

10%

15%

primaryendpt

MI large MI urgent TVR thromboticbailout

death

placebo

eptifibatide

Primary Endpoint AnalysisPrimary Endpoint AnalysisEvents to 48 HoursEvents to 48 Hours

Primary Endpoint AnalysisPrimary Endpoint AnalysisEvents to 48 HoursEvents to 48 Hours

52%p=0.02952%

p=0.029

40%p=NS40%p=NS

33%p=0.06433%

p=0.064

40%p=0.001540%

p=0.0015

37%p=0.001537%

p=0.0015

(MB (MB >>5x)5x)(MB (MB >>5x)5x)

n=2064n=2064

50%p=NS50%p=NS

ESPRIT Investigators. Lancet. 2000;356:2037–2044

Efficacy by Clinical SyndromeEfficacy by Clinical Syndrome30 Day death, MI, urgent TVR, bailout IIb/IIIa30 Day death, MI, urgent TVR, bailout IIb/IIIaEfficacy by Clinical SyndromeEfficacy by Clinical Syndrome

30 Day death, MI, urgent TVR, bailout IIb/IIIa30 Day death, MI, urgent TVR, bailout IIb/IIIa

8.0%

12.3%

6.1%7.3%

8.6%

11.4%

8.3%

20.4%

12.1%

17.1%

0%

5%

10%

15%

20%

25%

stableangina

ACS >48hr

ACS <48hr

ST MI <7d

positive fctstudy

placebo

eptifibatide

8.0%

12.3%

6.1%7.3%

8.6%

11.4%

8.3%

20.4%

12.1%

17.1%

0%

5%

10%

15%

20%

25%

stableangina

ACS >48hr

ACS <48hr

ST MI <7d

positive fctstudy

placebo

eptifibatide

50%p=0.034NNT=14

50%p=0.034NNT=14

41%p=0.028NNT=18

41%p=0.028NNT=18

23%p=0.3023%

p=0.30

44%p=NS

NNT=11

44%p=NS

NNT=11

31%p=NS31%p=NS

n=794 n=794 (38%)(38%) n=664 n=664 (32%)(32%) n=279 n=279 (14%)(14%) n=93 n=93 (5%)(5%) n=187 n=187 (9%)(9%) Puma JA et al. J Am Coll Cardiol. 2006;47:715–718.

De

ath

, MI,

urg

ent T

VR

Number of stents

40%

30%

20%

10%

01 2 ≥3

P=0.001

MACE at 48º by Number of Stents

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

EptifibatidePlacebo

<15 15 to <18 mm 18 to <30 mm

P=0.030

≥30 mm

P=0.003

MACE at 48º by Stent Length40%

30%

20%

10%

0

EptifibatidePlacebo

Total length of implanted stent(s)

De

ath

, MI,

urg

ent T

VR

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

≤2.5 mm >2.5 to <3.5 mm ≥3.5 mm

P=0.002

40%

30%

20%

10%

0

EptifibatidePlacebo

De

ath

, MI,

urg

ent T

VR

Stent diameter

MACE at 48º by Stent Diameter

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

<141 141 to <188 188 to <292 ≥292

P=0.039

P=0.002

40%

30%

20%

10%

0

EptifibatidePlacebo

MACE at 48º by Stented Vessel AreaD

ea

th, M

I, u

rgen

t TV

R

Stented vessel area (mm2)

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

Total stent length (mm)

Me

an

ste

nt d

iam

ete

r (m

m)

20

6

5

4

3

2

1

040 60 80 100 120

Stent Diameter vs. Length

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

1 2 ≥3

P=0.005

40%

30%

20%

10%

0

EptifibatidePlacebo

MACE at 1 year by Number of StentsD

ea

th, M

I, T

VR

Number of stents

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

P=0.034

P=0.024

<15 15 to <18 mm 18 to <30 mm ≥30 mm

40%

30%

20%

10%

0

EptifibatidePlacebo

MACE at 1 year by Stent LengthD

ea

th, M

I, T

VR

Total length of implanted stent(s)

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

≤2.5 mm >2.5 to <3.5 mm ≥3.5 mm

P=0.005

40%

30%

20%

10%

0

EptifibatidePlacebo

MACE at 1 year by Stent DiameterD

ea

th, M

I, T

VR

Stent diameter

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

<141 141 to <188 188 to <292 ≥292

P=0.023

40%

30%

20%

10%

0

EptifibatidePlacebo

MACE at 48º by Stented Vessel AreaD

ea

th, M

I, T

VR

Stented vessel area (mm2)

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

0.1 1 10

Eptifibatide Better Placebo BetterNumber of Stents

12≥3

Stent Length (mm)<1515 – <1818 – <30≥30

Stent Diameter (mm)≤2.5>2.5 – <3.5≥3.5

Stented Vessel Area (mm2)<141141 – <188188 – <292≥292

Odds Ratios of MACE at 48º

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

0.1 1 10

Number of Stents12≥3

Stent Length (mm)<1515 – <1818 – <30≥30

Stent Diameter (mm)≤2.5>2.5 – <3.5≥3.5

Stented Vessel Area (mm2)<141141 – <188188 – <292≥292

Eptifibatide Better Placebo Better

Odds Ratios of MACE at 1 year

Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

Stent Parameters and MACE

In the placebo group, MACE rates increased as the number of stents increased, with increasing total length of stent, and with total stented vessel area relationship nearly linear with total stented

vessel area

Risk gradient significantly flattened by eptifibatide

Eptifibatide had significant efficacy with: >2 stents >18 mm total stent length