GP IIb/IIIa Inhibition in STEMI: Growing Clinical Trial Evidence

VBWG

Antman EM et al. Circulation. 2004;110:588-636.Modified from Keeley EC et al. Lancet. 2003;361:13-20.

Meta-analysis of 23 trials; N = 7739

PCI Fibrinolysis

Frequency(%)

Deathno SHOCK

data

Recur ischemia

Total stroke

Hem stroke

Major bleed

Death, MI,

stroke

0

5

10

15

20

25

Death ReMI

PCI vs fibrinolysis in STEMI patients: Short-term clinical outcomes

VBWG

Antman EM et al. Circulation. 2004;110:588-636.Modified from Keeley EC et al. Lancet. 2003;361:13-20.

Meta-analysis of 23 trials

PCI Fibrinolysis

Frequency(%)

Death, no SHOCK data

RecurMI

Recur ischemia

Death MI stroke

Death0

5

10

15

20

25

30

35

PCI vs fibrinolysis in STEMI patients: Long-term clinical outcomes

VBWG

ACC/AHA STEMI guidelines: Assessing reperfusion options

Fibrinolysis Primary PCI

• Early presentation (≤3 hours from symptom onset)

• Invasive strategy not an option

• Delay to invasive strategy– Door-to-balloon exceeds door-to-

needle time by >1 hour– >90 minutes to balloon time

• High-volume lab with surgical backup

• High risk from STEMI

• Fibrinolysis contraindicated (excessive bleeding/ICH)

• Late presentation– Symptoms >3 hours prior

• STEMI diagnosis in doubt

ICH = intracranial hemorrhage Antman EM et al. Circulation. 2004;109:2480-6.

VBWG

Chesebro JH et al. Circulation. 1987;76:142-54.

TIMI 0 Complete occlusion

TIMI 1 Penetration of obstruction by contrast but no distal perfusion

TIMI 2 Perfusion of entire artery but delayed flow

TIMI 3 Full perfusion, normal flow

Mortality is reduced with better flow

TIMI flow grade

VBWG

Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824-6.

Meta-regression analysis of 21 trials

Absolute risk

difference in death

(%)

Circle sizes reflect study sample size Solid line = weighted meta-regression

P = 0.006

62 minutes Benefit:Favors PCI

Harm:Favors lytics

PCI-related time delay (minutes)

–5

0

5

10

15

0 20 40 60 80 100

Mortality benefit of primary PCI declines with PCI-related time delay

VBWG

Beygui F, Montalescot G. Eur Heart J. 2005;7(suppl):110-4.

Major considerations for pharmacologic approaches to facilitate primary PCI

• Delay between presentation with STEMI and primary PCI vs progressive nature of ischemia-related necrosis

• Inverse relationship between time-to-reperfusion and extent of salvaged myocardium and survival

• Relationship between restoration of coronary flow and recovery of contractility and survival after STEMI

• Facilitated PCI strategy utilizing GP IIb/IIIa inhibition or fibrinolytic therapy provides a degree of coronary reperfusion when PCI is not immediately available

VBWG

Zeymer U et al. Eur Heart J. 2005;26:1971-

7.

Patency (%)

0

10

20

50

60

70

80

TIMI 3

30

40 34.0

10.2

TIMI 2

7.6

22.4

TIMI 0/1

58.4

67.4P = 0.01

Early administration (n = 53)

Late or no administration (n = 49)

INTegrilin in Acute Myocardial Infarction

INTAMI pilot trial: Early eptifibatide improves TIMI 3 flow before PCI for STEMI

VBWG

Zeymer U et al. Eur Heart J. 2005;26:1971-7.www.timi.org

Early Late or no GP IIb/IIIa inhibitor

0

10

20

30

40

Zorman

Reo-Mobile

ERAMI ReoPro-bridging

ADMIRAL Cutlip TIGER-PA

On-TIME

INTAMI

TIMI 3patency before PCI (%)

N = 109 100 69 55 300 60 100 487 102 316

Abciximab Tirofiban

TITAN

Eptifibatide

TIMI 3 patency before PCI in trials of early vs late/no GP IIb/IIIa inhibitors in STEMI

VBWG

GP IIb/IIIa inhibitors for primary PCI

Brener SH et al. Circulation. 1998;98:734-41.Neumann FJ et al. J Am Coll Cardiol. 2000;35:915-21.

Montalescot G et al. N Engl J Med. 2001;344:1895-1903.Antoniucci D et al. J Am Coll Cardiol. 2003;42:1879-85.

30-day death, recurrent MI, or urgent revascularization

*Outcome also includes stroke

11.2

5.8

10.5

5

14.6

6

10.5

4.5

0

2

4

6

8

10

12

14

16

RAPPORT ISAR-2 ADMIRAL* ACE

P = 0.02

P = 0.01

N =

P = 0.04P = 0.03

%

Placebo GP IIb/IIIa inhibitor

483 401 300 400

VBWG

Beygui F, Montalescot G. Eur Heart J Suppl. 2005;7(suppl I):I10-4.

Facilitated PCI in STEMI

• Early administration of GP IIb/IIIa inhibitors is associated with significant flow restoration, potentially better myocardial reperfusion, and no significant increase in major bleeding

• Early GP IIb/IIIa facilitation strategy may be recommended in STEMI patients who are candidates for primary PCI

• Benefits of GP IIb/IIIa therapy in primary PCI for STEMI demonstrated in large clinical trials include improvement in pre-PCI coronary flow, angiographic parameters, and ischemic outcomes and mortality

• More data from large-scale clinical trials are needed to determine the risks and benefits of facilitated PCI with GP IIb/IIIa inhibitors + fibrinolytics