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GP IIb/IIIa Inhibition in STEMI: Growing Clinical Trial Evidence. PCI vs fibrinolysis in STEMI patients: Short-term clinical outcomes. Meta-analysis of 23 trials; N = 7739. 25. 20. Frequency (%). 15. 10. 5. 0. Recur ischemia. Death. Death no SHOCK data. ReMI. Total stroke.
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GP IIb/IIIa Inhibition in STEMI: Growing Clinical Trial Evidence
PCI vs fibrinolysis in STEMI patients: Short-term clinical outcomes Meta-analysis of 23 trials; N = 7739 25 20 Frequency (%) 15 10 5 0 Recur ischemia Death Death no SHOCKdata ReMI Total stroke Hem stroke Major bleed Death, MI, stroke PCI Fibrinolysis Antman EM et al. Circulation. 2004;110:588-636. Modified from Keeley EC et al. Lancet. 2003;361:13-20.
PCI vs fibrinolysis in STEMI patients: Long-term clinical outcomes Meta-analysis of 23 trials 35 30 25 Frequency (%) 20 15 10 5 0 Death MI stroke Death Death, no SHOCK data RecurMI Recur ischemia PCI Fibrinolysis Antman EM et al. Circulation. 2004;110:588-636. Modified from Keeley EC et al. Lancet. 2003;361:13-20.
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 ACC/AHA STEMI guidelines: Assessing reperfusion options Fibrinolysis Primary PCI ICH = intracranial hemorrhage Antman EM et al. Circulation. 2004;109:2480-6.
TIMI flow grade 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 Chesebro JH et al. Circulation. 1987;76:142-54.
Mortality benefit of primary PCI declines with PCI-related time delay Meta-regression analysis of 21 trials 15 Circle sizes reflect study sample size Solid line = weighted meta-regression 10 Absolute risk difference in death (%) P = 0.006 5 62 minutes Benefit:Favors PCI 0 Harm:Favors lytics –5 0 20 40 60 80 100 PCI-related time delay (minutes) Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824-6.
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 Beygui F, Montalescot G. Eur Heart J. 2005;7(suppl):110-4.
INTAMI pilot trial: Early eptifibatide improves TIMI 3 flow before PCI for STEMI INTegrilin in Acute Myocardial Infarction 80 67.4 70 P = 0.01 58.4 60 50 Patency (%) 40 34.0 30 22.4 20 10.2 7.6 10 0 TIMI 3 TIMI 2 TIMI 0/1 Early administration (n = 53) Late or no administration (n = 49) Zeymer U et al. Eur Heart J. 2005;26:1971-7.
TIMI 3 patency before PCI in trials of early vs late/no GP IIb/IIIa inhibitors in STEMI 40 Abciximab Tirofiban Eptifibatide 30 TIMI 3patency before PCI (%) 20 10 0 Zorman Reo-Mobile ERAMI ReoPro-bridging ADMIRAL Cutlip TIGER-PA On-TIME INTAMI TITAN N = 109 100 69 55 300 60 100 487 102 316 Early Late or no GP IIb/IIIa inhibitor Zeymer U et al. Eur Heart J. 2005;26:1971-7. www.timi.org
GP IIb/IIIa inhibitors for primary PCI 30-day death, recurrent MI, or urgent revascularization P = 0.01 16 14.6 P = 0.03 14 P = 0.02 P = 0.04 11.2 12 10.5 10.5 10 % 8 6 5.8 5 6 4.5 4 2 0 RAPPORT ISAR-2 ADMIRAL* ACE N = 483 401 300 400 Placebo GP IIb/IIIa inhibitor 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. *Outcome also includes stroke
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 Beygui F, Montalescot G. Eur Heart JSuppl. 2005;7(suppl I):I10-4.