gp iib/iiia inhibition in stemi: growing clinical trial evidence
TRANSCRIPT
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