Transcript Use of Glycoprotein IIb/IIIa Receptor Inhibitors in Acute MI

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
STANFORD
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?
STANFORD
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
STANFORD
RAPPORT
ReoPro in Acute myocardial infarction and
Primary PTCA Organization Randomized Trial
• N=483
• Abciximab in the ER or cath lab
– 30-day MACE
Control
Abciximab
P value
Any drug
(n=409)
Int to treat
(n=483)
12.0
4.6
0.005
11.2
5.8
0.038
• 6-month MACE: no difference
STANFORD
ADMIRAL
Abciximab before Direct angioplasty and stenting
in Myocardial Infarction Regarding Acute and
Long-term follow-up
Event
*Abciximab Placebo
(n=150)
(n=150)
Death, MI, urgent
TVR at 30 d
P
10.7%
20.0%
0.03
21%
10%
<0.01
24 h
86%
78%
<0.03
LVEF 24 h
55%
51%
30 d
63%
55%
TIMI-3 initial
*26% received in ambulance or ER
STANFORD
Patients With TIMI-3 Flow
GRAPE
Glycoprotein Receptor Antagonist
Patency Evaluation Pilot (N=60)
50%
P < 0.0001
40%
30%
32%
20%
10%
0%
23%
23%
18%
8%
GRAPE SPEED TIMI-14A
(n=60) (n=26) (n=31)
angio at 45 min
60 min
90 min
All Abciximab
(n=117)
GUSTO-IIb
(n=510)
115 min
STANFORD
TIGER-PA
Pilot
• 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
STANFORD
TIGER-PA
Pilot
• Targets
– 100 patients planned
– 40% power to detect a 15% difference
in the TIMI frame count and flow
STANFORD
TIGER-PA
Pilot
• Inclusion criteria
– Chest pain within 12 hours of onset
– 1 mm ST-elevation in 2 or more
contiguous leads or new LBBB
STANFORD
TIGER-PA
Pilot
• Exclusion criteria
– Age <18
– 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
STANFORD
TIGER-PA
Pilot
• 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 < 150K
STANFORD
TIGER-PA
Pilot
• Study design
– 1:1 open-label randomization to tirofiban in
the ER (early) or in the cath lab (delayed)
– No PTCA in early arm if culprit lesion <50%
– Delayed tirofiban if PTCA to be performed
STANFORD
TIGER-PA
Pilot
Acute myocardial infarction
Meets inclusion criteria
Tirofiban in ER
No tirofiban in ER
Angiogram
Angiogram
PTCA/stent
Final angiogram
No PTCA if lesion
<50%
No PTCA
Tirofiban if PTCA
to be performed
Final angiogram
STANFORD
TIGER-PA
Pilot
• 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 investigator’s discretion
STANFORD
TIGER-PA
Pilot
• 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
STANFORD
TIGER-PA
Pilot
• Endpoints
– Primary endpoint
• TIMI flow
• TIMI frame counts
– Secondary endpoint
• Bleeding
– Minor: Hct10% or Hb3 g/dL
– Major: Hct15% or Hb5 g/dL
– Thrombocytopenia (PLTs< 90000)
STANFORD
TIGER-PA
Pilot
• Endpoints
– Tertiary endpoint (30 days)
• Repeat coronary revascularization
– Urgent vs nonurgent
• Death (from any cause)
• New MI (CPK >2x normal)
• Hospitalization for refractory ischemia
STANFORD
TIGER-PA
Pilot
• Adjuvant therapy
– If a stent is placed, ticlopidine 250 mg po bid
or clopidogrel 75 mg po qd x 14 d
– Heparin may be stopped temporarily for early
sheath removal
STANFORD
TIGER-PA
Pilot
• 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
STANFORD
TIGER-PA
Pilot
•
•
•
•
•
•
•
N=54
30 ER, 24 cath lab
Patients to date 54 (registry=83)
Average age
65 ± 13 years
Male:female
7:2
Anterior 22, lateral 7, inferior 25
Mean time from ER to cath lab: 83 minutes
Mean time for tirofiban to cath lab: 34 minutes
STANFORD
TIGER-PA
Pilot
Initial CTFC
TGF
Mean = 34 min
* P=0.01
3
* P=0.002
40
2
20
1
0
0
ER Cath Lab
ER Cath Lab
TGF
CTFC
60
STANFORD
TIGER-PA
Pilot
Initial TGF
40
# Patients
30
TGF
TIMI-3
*
TIMI-2
TIMI-0 or 1
20
10
* P=0.002
0
ER
Cath Lab
STANFORD
TIGER-PA
Pilot
• 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.
STANFORD
TIGER-PA
Pilot
Platelet Substudy
• 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
STANFORD
TIGER-PA
Pilot
Platelet Substudy
% platelet inhibition
100
80
60
40
20
0
Baseline Post Bolus 20 min
40 min
EOC
STANFORD
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
STANFORD
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
STANFORD