Tirofiban Given in the Emergency Room Before Primary Angioplasty TIGERPA Pilot Study

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Tirofiban Given in the Emergency Room Before
Primary Angioplasty (TIGER-PA) Pilot Study

• David P. Lee, MD, Alan C. Yeung, MD,
• Donald Schreiber, MD, Michelle Huston, MD

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GP IIb/IIIa Inhibitors in Acute MI

• Key questions regarding new adjuvant therapies
• Can we improve reperfusion times?
• Can we improve flow after reperfusion?
• Can we limit infarct size and thus complications?

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GP IIb/IIIa Inhibitors in Acute MI

• Why a GP IIb/IIIa inhibitor could work
• Early potent antiplatelet therapy
• Adjunctive use in PCI improves outcomes
• May improve flow
• Relatively safe to use

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RAPPORTReoPro in Acute myocardial infarction and
Primary PTCA Organization Randomized Trial

• N483
• Abciximab in the ER or cath lab
• 30-day MACE Any drug Int to treat (n409)
  (n483)
• Control 12.0 11.2
• Abciximab 4.6 5.8
• P value 0.005 0.038
• 6-month MACE no difference

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ADMIRALAbciximab before Direct angioplasty and
stenting in Myocardial Infarction Regarding
Acute and Long-term follow-up

• Event Abciximab Placebo (n150) (n150) P
• Death, MI, urgent TVR at 30 d 10.7 20.0 0.03
• TIMI-3 initial 21 10
• 24 h 86 78
• LVEF 24 h 55 51
• 30 d 63 55

26 received in ambulance or ER
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GRAPEGlycoprotein Receptor Antagonist Patency
Evaluation Pilot (N60)
P 32
Patients With TIMI-3 Flow
23
23
18
8
GRAPE(n60) 45 min
SPEED(n26) 60 min
TIMI-14A(n31) 90 min
All Abciximab(n117)
GUSTO-IIb(n510) 115 min
angio at
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TIGER-PAPilot

• Goals
• To test the safety and efficacy of tirofiban in
  the setting of an acute MI
• To compare early adjunctive use of tirofiban
  before primary PCI with peri-PCI use

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TIGER-PAPilot

• Targets
• 100 patients planned
• 40 power to detect a 15 difference in the TIMI
  frame count and flow

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TIGER-PAPilot

• Inclusion criteria
• Chest pain within 12 hours of onset
• ?1 mm ST-elevation in 2 or more contiguous
  leads or new LBBB

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TIGER-PAPilot

• Exclusion criteria
• Age
• Major surgery, GI or GU bleed within 30 days
• CVA within 1 year or with residual deficit
• Known bleeding diathesis
• Known intracranial disease
• Cardiogenic shock

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TIGER-PAPilot

• Exclusion criteria
• Uncontrolled HTN (SBP 180, DBP 100)
• Prolonged CPR
• Thrombolysis within 24 hours
• Concomitant use of a GP IIb/IIIa inhibitor
• Hemorrhagic retinopathy
• PLTs

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TIGER-PAPilot

• Study design
• 11 open-label randomization to tirofiban in the
  ER (early) or in the cath lab (delayed)
• No PTCA in early arm if culprit lesion
• Delayed tirofiban if PTCA to be performed

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TIGER-PAPilot
Acute myocardial infarction
Meets inclusion criteria
Tirofiban in ER
No tirofiban in ER
Angiogram
Angiogram
Final angiogram
Final angiogram
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TIGER-PAPilot

• Dosing
• Tirofiban 10 µg/kg over 3 minutes, then 0.15
  µg/kg/min x 24 hours
• Heparin
• Early 70 U/kg IV bolus, then 7.5 U/kg/h
• Delayed 100 U/kg IV bolus, then 10 U/kg/h
• All other medications including NTG, ?-blockers
  at the investigators discretion

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TIGER-PAPilot

• Laboratories
• Baseline 6 h 12 h 18 h 24 h
• Hb X - X - X
• Hct X - X - X
• PLT X - X - X
• CPK X X X X X
• CPK-MB X X X X X

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TIGER-PAPilot

• Endpoints
• Primary endpoint
• TIMI flow
• TIMI frame counts
• Secondary endpoint
• Bleeding
• Minor Hct ³10 or Hb ³3 g/dL
• Major Hct ³15 or Hb ³5 g/dL
• Thrombocytopenia (PLTs

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TIGER-PAPilot

• Endpoints
• Tertiary endpoint (30 days)
• Repeat coronary revascularization
• Urgent vs nonurgent
• Death (from any cause)
• New MI (CPK 2x normal)
• Hospitalization for refractory ischemia

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TIGER-PAPilot

• Adjuvant therapy
• If a stent is placed, ticlopidine 250 mg po bid
  or clopidogrel 75 mg po qd x ³14 d
• Heparin may be stopped temporarily for early
  sheath removal

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TIGER-PAPilot

• Data analysis
• Primary endpoint
• Blinded observer for TIMI frame count and flow
  at baseline and after PTCA
• Secondary endpoint
• Data monitoring for CBC and CPKs
• Safety monitor for bleeding events
• Tertiary endpoint
• Clinical follow-up by chart review and telephone

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TIGER-PAPilot
INTERIM

• N54 30 ER, 24 cath lab
• Patients to date 54 (registry83)
• Average age 65 13 years
• Malefemale 72
• Anterior 22, lateral 7, inferior 25
• Mean time from ER to cath lab 83 minutes
• Mean time for tirofiban to cath lab 34 minutes

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TIGER-PAPilot
INTERIM
Initial CTFC
TGF
Mean 34 min
P0.01
60
3
P0.002
40
2
CTFC
TGF
20
1
0
0
ER
Cath Lab
ER
Cath Lab
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TIGER-PAPilot
INTERIM
Initial TGF
TGF
40
TIMI-3

30
TIMI-2
TIMI-0 or 1
20
Patients
10
P0.002
0
ER
Cath Lab
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TIGER-PAPilot
INTERIM

• Complications
• ER Cath Lab
• Minor bleeding 4 2
• Major bleeding 1 1
• 30 d MACE 1 2

30-day MACE include 1 patient in each group
admitted for chest pain and 1 patient who had SAT
and repeat PCI at 6 days in the cath lab group
with no deaths.
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TIGER-PAPilot Platelet Substudy
INTERIM

• 10 patients in the Cath Lab group underwent
  measurements of platelet inhibition with the
  Accumetrics Ultegra RPFA while in the Cath Lab
• Time points baseline, 20m, 40m, EOC

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TIGER-PAPilot Platelet Substudy
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TIGER-PA

• Summary
• Pilot study to determine safety and efficacy of
  tirofiban given in the ER before primary PTCA
• Tirofiban given early in the ER may lead to
  further improvement in TIMI flow and frame count
  compared with tirofiban given in the cath lab

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Summary

• GP IIb/IIIa receptor inhibitors may be beneficial
  as an adjunct in acute MI
• Safe and well tolerated
• Further large-scale trials are needed to better
  delineate a long-term benefit