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Intravenous GP IIb/IIIa Inhibitors

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Intravenous GP IIb/IIIa Inhibitors Abciximab (ReoPro) Has a rapid, high affinity to platelets within minutes Dissociation slowly from GP IIb/IIIa receptor Clears ... – PowerPoint PPT presentation

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Title: Intravenous GP IIb/IIIa Inhibitors


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Intravenous GP IIb/IIIa Inhibitors
  • Abciximab (c7E3 Fab, ReoPro) Human- murine
    chimeric monoclonal Fab antibody fragment
  • Eptifibatide (Integrilin) A cyclic
    heptapeptide based on the Lys-Gly-Asp (KGD)
    amino acid sequence
  • Tirofiban (Aggrastat) Tyrosine derivative
    non-peptide mimetic inhibitor

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Intravenous GP IIb/IIIa InhibitorsAbciximab
(ReoPro)
  • Has a rapid, high affinity to platelets within
    minutes
  • Dissociation slowly from GP IIb/IIIa receptor
  • Clears rapidly from plasma but remains bound to
    circulating platelets up to 21 days
  • Binding to IIb/IIIa receptor is non-specific and
    has equal affinity for the vitronectin receptor
    which appears to play a role in cell adhesion,
    migration and proliferation

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Intravenous GP IIb/IIIa Inhibitors
Reopro Integrilin Aggrastat
Structure Monoclonal antibody Peptide Non-peptide Tyrosine derivative
Specificity to IIb/IIIa receptor Also binds to vitronectin Very Very
Platelet bound t1/2 Hours Seconds Seconds
Platelet recovery 12-36 Hrs 4 Hrs 4 Hrs
Plasma t1/2 Minutes 2.5 Hrs 1.8 Hrs
of dose in bolus 75 lt2-16 lt2-5
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IV IIb/IIIa Inhibitors and Time course of Action
on Platelets
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N 2099
N 1265
N 2792
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EPISTENT
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EPISTENT
Stent Placement
Placebo/Stent
Abx
/Stent
Abx
/Balloon
Placebo/Stent
Abx
/Stent
Abx
/Balloon
No. Patients
No. Patients
809
794
796
Stent Placed ()
95.3
96.9
Stent Placed ()
19.1
No. Stents/Pt ()
No. Stents/Pt ()
1
69.6
73.8
1
66.4
2
21.9
20.2
2
23.0
3
5.7
4.5
3
7.2
³
³
2.7
1.6
4
3.3
4
Maximum Balloon
Maximum Balloon
Inflation Pressure (mm)
16.0
16.0
Inflation Pressure (mm)
16.0
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EPISTENT
o
Death, MI, or Urgent Intervention
p 0.051
p 0.007
p lt 0.001
p lt 0.001
Reduction
Reduction
vs
vs
Stent Only
Stent Only
Abciximab Stent
47
51
Abciximab Stent
47
51
Abciximab Only
24
37
Abciximab Only
24
37
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EPISTENT
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EPISTENT
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EPISTENT
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EPISTENT
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EPISTENT
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EPISTENT
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EPISTENT
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EPISTENT
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World Wide Effect of Reopro if Used in All PTCA
Procedures - Extrapolation from EPISTENT
No. of Lives Saves gt2500 No. of MIs
Prevented gt40,000 No. of emergency
Revascularisation gt6500 Prevented
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RESTORE Trial - Tirofiban for Patients with
UA or acute MI undergoing PTCA
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Placebo
24
Tirofibin
10.5
p0.052
10
N 2139
)
8
8
Treatment was given for 36 hrs
)
Baseline characteristics or risk
)
stratification were not predictive
6
of treatment effect
Composite Endpoint (Death, MI, Urgent R
The differences in death and MI
)
rates was maintained over 6
months but the rate of
4
revascularisation remained
unchanged
Subgroup angiography study of
)
2
600 pts should no effect on
restenosis
0
Treatment Arms
R Revascularisation.
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Overview of Randomised Trials of GP IIb/IIIa
Inhibitors During Coronary Intervention
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RAPPORT TRIAL - Reopro For Primary
PTCA
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N 483
p 0.038
0.02
48
30
28.2
28.1
25
20
Placebo
16.6
Event Rate ()
Reopro
15
11.2
9.5
10
5.8
5
0
Endpoint A
Endpoint B
Bleeding Complications
Endpoint A Death, recurrent MI, urgent repeat
TVR at 30 days. B Death, recurrent MI, any
repeat TVR (inc elective ones) at 6 month
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GP IIb/IIIa Inhibitors for Coronary Intervention
  • In gt15,000 patients GP IIb/IIIIa blockade shown
    to reduce risk of important acute ischaemic
    events by gt50-60 during coronary intervention
  • The treatment effect extends to each of the
    components of the composite clinical endpoints
    (Death, MI, and emergency revascularisation)
  • The inhibition of ischaemic events is achieved
    early (12-48 hrs) and maintained up to 3 yrs

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GP IIb/IIIa Inhibitors for Coronary Intervention
  • All patients regardless of their demographics,
    clinical, angiograhic, or procedural
    characteristic benefit
  • Patients with UAP and Diabetics obtain the
    greatest benefit
  • There may be heterogeneity among the different
    IIb/IIIa inhibitors. The greatest impact has been
    shown with Reopro. This may be due to its
    non-specific binding ability and its different
    pharmocokinetic profile

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GP IIb/IIIa Inhibitors for Coronary Intervention
  • Reopro may be specially effective in reducing TVR
    and therefore restenosis in diabetes in
    association with coronary stenting but influence
    of GP IIb/IIIa inhibitors on restenosis in other
    groups remain unclear
  • Safety of these drugs is increased by keeping ACT
    200 during procedure and avoiding
    post-procedural heparin with early sheath removal
  • Economical aspects of this therapy needs to be
    evaluated

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Who should have Reopro during Coronary
Intervention
  • Patients with UAP at rest with ECG changes, or
    Refractory angina or Post MI angina particularly
    if
  • Diabetic
  • Clot present
  • TIMI 3 flow not achieved
  • Troponin level is raised
  • ? In Rescue / Salvage PTCA

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EPISTENT
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EPISTENT
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EPISTENT
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EPISTENT
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EPISTENT
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EPISTENT
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