Rabih R. Azar, MD, MSc, FACC Director of Cardiovascular Research
Hotel Dieu de France Hospital Associate Professor of Medicine Saint
Joseph University School of Medicine Beirut, Lebanon NSTEMI:
GPIIB/IIIA Inhibitors & Emerging Antiplatelets: Where Do We
Stand? Slide 2 Role of the Platelets in Thrombosis UA/NQMI:
Partially-occlusive thrombus (primarily platelets) Intra-plaque
thrombus (platelet dominated) Plaque core ST MI: occlusive thrombus
(platelets, red blood cells, and fibrin) Intra-plaque thrombus
(platelet dominated) Plaque core SUDDEN DEATH Adapted from Davies
MJ. Circulation. 1990; 82 (supl II): 30-46. Slide 3 GP IIb/IIIa
Receptor Activation Pathway ASPIRIN ASPIRIN HEPARINS ASPIRIN
ASPIRIN ASPIRIN ASPIRIN GP IIb/IIIa Thickness of line indicates
strength of activator 5HT PAF Epi Thrombin ADP TXA 2 ASPIRIN
Vasopressin Collagen Fibrinogen PLATELET PLATELET CLOPIDOGREL Slide
4 Platelet-fibrinogen interaction Slide 5 5 Time after bolus
(minutes) 15304560120 0 60 80 100 abciximab plus infusion tirofiban
10 g/kg bolus plus infusion 85% Inhibition of Light Transmission
Aggregation Induced by 20 M ADP After Treatment with Tirofiban or
Abciximab Inhibition of Maximal Aggregation (%) TARGET DOSE Slide 6
6 Time after bolus (minutes) 15304560120 0 60 80 100 abciximab plus
infusion tirofiban 10 g/kg bolus plus infusion tirofiban 20 g/kg
bolus plus infusion tirofiban 25 g/kg bolus plus infusion 85%
Inhibition of Light Transmission Aggregation Induced by 20 M ADP
After Treatment with Tirofiban or Abciximab Inhibition of Maximal
Aggregation (%) TARGET DOSE SHBD Slide 7 EPIC: 3-year Outcome JAMA
1997;278:478 Slide 8 8 PRISM-PLUS: Study Design Endpoints Primary:
Composite death, MI, refractory ischemia, rehospitalization at 7
days Secondary: Death, MI, refractory ischemia, rehospitalization
at 48 h, 30 days, and 6 months Safety: Major bleeding (>4.0 g/dL
decrease in Hb, blood transfusion >2 U, need for corrective
surgery, or intracranial or retroperitoneal hemorrhage, or any
combo) Endpoints Primary: Composite death, MI, refractory ischemia,
rehospitalization at 7 days Secondary: Death, MI, refractory
ischemia, rehospitalization at 48 h, 30 days, and 6 months Safety:
Major bleeding (>4.0 g/dL decrease in Hb, blood transfusion
>2 U, need for corrective surgery, or intracranial or
retroperitoneal hemorrhage, or any combo) AGGRASTAT 0.4 g/kg/min
for 30 min, then 0.10 g/kg/min maintenance + heparin (n=773)
AGGRASTAT 0.4 g/kg/min for 30 min, then 0.10 g/kg/min maintenance +
heparin (n=773) Heparin 5000 U loading, then 1000 U maintenance
(n=797) Heparin 5000 U loading, then 1000 U maintenance (n=797)
Randomization UA or NSTEMI patients Chest pain within 12 h and ECG
abnormalities or elevated CK-MB UA or NSTEMI patients Chest pain
within 12 h and ECG abnormalities or elevated CK-MB 48 h PRISM-PLUS
Study Investigators. N Engl J Med. 1998;338(21):1488-1497. Slide 9
PRISM PLUS: Results NEJM 1998;338:1488 Slide 10 Slide 11 Slide 12
Brenner et al. Circulation 1998;98:734 RAPPORT: Abciximab in
primary PTCA reduces death/MI/urgent TVR at 30 days Slide 13
Synergy between abciximab and stenting in primary angioplasty for
acute MI. Event free suvival (death, acute coronary syndromes, TVR)
Azar et al. J Am Coll Cardiol 1998;32:1996 Slide 14 GP IIb/IIIa
Receptor Activation Pathway ASPIRIN ASPIRIN HEPARINS ASPIRIN
ASPIRIN ASPIRIN ASPIRIN GP IIb/IIIa Thickness of line indicates
strength of activator 5HT PAF Epi Thrombin ADP TXA 2 ASPIRIN
Vasopressin Collagen Fibrinogen PLATELET PLATELET CLOPIDOGREL Slide
15 Slide 16 Slide 17 Does Clopidogrel Eliminate the Need for
GPIIb/IIIa Antogonists? Slide 18 Treatment with AGGRASTAT provides
greater flexibility for early surgical procedures, transfer, or
discharge Adapted from Kereiakes DJ et al. Am Coll Cardiol
1996;27(3):536-542 0.5 60 100 % inhibition Fast-On Approximate %
platelet aggregation blocked Fast-Off Return to baseline of
platelet function Hours of infusionHours postinfusion 80 40 20
122448 0 60 100 80 40 20 248 0 End infusion 3567 % inhibition Slide
14 Slide 19 Slide 20 Slide 21 EPISTENT: Effect of Thienopyridine
Pretreatment Placebo No Pretreat Placebo Pretreat Abcix No Pretreat
Abcix Pretreat 42% (P=0.028 ) 33% (P=0.033 ) Steinhubl S et al.
Circulation 2001;103:1403-9 Slide 22 Slide 23 Slide 24 Slide 25
Slide 26 Slide 27 Slide 28 28 Slide 29 29 Tirofiban vs Placebo 00
22 44 66 Death 30 Days Death Death 5 Months Death 3.03.0 2.02.0 OR=
0.66 P
