TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
Phases of TrialPhases of Trial
ControlControl InvestigationalInvestigational
Accel tPAAccel tPA
Accel tPAAccel tPA
rPA (10 +10 U)rPA (10 +10 U)
No lyticNo lytic
Abx +Abx +
tPAtPA
SKSK
Abx + 50 mg tPA + LD/VLD HeparinAbx + 50 mg tPA + LD/VLD Heparin
AbxAbx + + rPA + LD/VLD Heparin rPA + LD/VLD Heparin
tPA Phase (N= 888)tPA Phase (N= 888) (Circ 99 : 2720,1999)(Circ 99 : 2720,1999)
rPA Phase (N=299)rPA Phase (N=299)
tPA + rPA Pooled Database (N=1187)tPA + rPA Pooled Database (N=1187)
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
ST ST , lytic eligible, < 12 h , lytic eligible, < 12 h
ControlControlFull Dose Lytic:Full Dose Lytic:
tPA 100 mgtPA 100 mgoror
rPA 10 + 10 UrPA 10 + 10 U
Reduced Dose LyticReduced Dose Lytic
tPA, SK,rPAtPA, SK,rPA
No AbciximabNo Abciximab AbxAbx: bolus 0.25 mg/kg: bolus 0.25 mg/kg inf 0.125 inf 0.125 g/kg/min x 12 hg/kg/min x 12 h
STD HeparinSTD Heparin (70 U/kg ; 15 U/kg/h) (70 U/kg ; 15 U/kg/h)
ASAASA
Low Dose HeparinLow Dose Heparin (60 U/kg ; 7 U/kg/h) (60 U/kg ; 7 U/kg/h)
Very Low Dose HeparinVery Low Dose Heparin (30 U/kg ; 4 U/kg/h) (30 U/kg ; 4 U/kg/h)
Angio (90 min) , In Hospital Events, 30 day F/UAngio (90 min) , In Hospital Events, 30 day F/U
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
TIMI 3 Flow (Core Lab) : 90 minTIMI 3 Flow (Core Lab) : 90 min
57
32 3042
3446
80
0
20
40
60
80
100
57
32 3042
3446
80
0
20
40
60
80
100
% Pts
% % PtsPts
TIMI 14TIMI 14TIMI 14 bolus 0.25 inf 0.125
bolus 0.25 bolus 0.25 inf 0.125inf 0.125
500K500K500K 750K750K750K 1.5M1.5M1.5MTIMI 1 + GUSTO 1
TIMI 1 + TIMI 1 + GUSTO 1GUSTO 1
tPA 100 mg
tPA tPA 100 mg100 mg
AbxAbxAbx SK 1.5 M U
SK 1.5 SK 1.5 M UM U
SK + Abx
SK + SK + AbxAbx
1.25M1.25M1.25M
UUU
152152 3131 44443131 4444429 55N =N =N =
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
TIMI 3 Flow (Core Lab) : 90 minTIMI 3 Flow (Core Lab) : 90 min
57 53
38
61 59 63
76 74 73
0
20
40
60
80
100
57 53
38
61 59 63
76 74 73
0
20
40
60
80
100
% Pts
% % PtsPts
20 mg20 20 mgmg 35 mg35 35 mgmg 50 mg50 50 mgmg
TIMI 14TIMI 14TIMI 14
tPAtPAtPA tPA + Abx tPA + Abx tPA + Abx
65 mg65 65 mgmg
bbb bbb bbbinf 30m
inf inf 30m30m
inf 30m
inf inf 30m30m
inf 60m
inf inf 60m60m
inf 60m
inf inf 60m60m
inf 60m
inf inf 60m60m
100 mg100 100 mgmg
Abx bolus Abx bolus 0.3 mg/kg0.3 mg/kg
152152 3636 4040 4949 2929 4646 2929 3939 3333N =N =N =
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
Safety Observations:Safety Observations:Dose Finding Phase N= 677Dose Finding Phase N= 677
Major Hemorrhage*Major Hemorrhage* (6.6% --mostly instr.; ICH = 1.2%) (6.6% --mostly instr.; ICH = 1.2%)tPA control tPA control 5%5%Abx aloneAbx alone 3%3%tPA + AbxtPA + Abx 6%6%SK + AbxSK + Abx 10% (dose related increase)10% (dose related increase)
ThrombocytopeniaThrombocytopenia <100K <100K <50K<50K tPA ControltPA Control 3%3% 0.6%0.6%Reperf. reg. with AbxReperf. reg. with Abx 7%7% 1.4%1.4%
Mortality (30 days)Mortality (30 days)
4.0% --no important differences across groups4.0% --no important differences across groups
Major Hemorrhage*Major Hemorrhage* (6.6% --mostly instr.; ICH = 1.2%) (6.6% --mostly instr.; ICH = 1.2%)tPA control tPA control 5%5%Abx aloneAbx alone 3%3%tPA + AbxtPA + Abx 6%6%SK + AbxSK + Abx 10% (dose related increase)10% (dose related increase)
ThrombocytopeniaThrombocytopenia <100K <100K <50K<50K tPA ControltPA Control 3%3% 0.6%0.6%Reperf. reg. with AbxReperf. reg. with Abx 7%7% 1.4%1.4%
Mortality (30 days)Mortality (30 days)
4.0% --no important differences across groups4.0% --no important differences across groups
*Major Hemorrhage = ICH, Retroperitoneal, or *Major Hemorrhage = ICH, Retroperitoneal, or Hg > 5 gm/dL Hg > 5 gm/dL
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
Abciximab Improves the Speed and Abciximab Improves the Speed and Extent of Thrombolysis: 60 + 90 min Extent of Thrombolysis: 60 + 90 min
TIMI 3 FlowTIMI 3 Flow
4557
4049
58 62 6374
0
20
40
60
80
100
4557
4049
58 62 6374
0
20
40
60
80
100 tPAtPAtPA tPA + Abx tPA + Abx tPA + Abx
bolusbolusbolus bolus + 30 min inf
bolus + bolus + 30 min inf30 min inf
bolus + 60 min inf
bolus + bolus + 60 min inf60 min inf
100 mg100 mg100 mg
trend trend trend
60m60m60m 90m90m90m 60m60m60m 90m90m90m60m60m60m 90m90m90m 60m60m60m 90m90m90m
p< 0.0002 p< 0.0002 p< 0.0002 p< 0.02 p< 0.02 p< 0.02
% Pts
% % PtsPts
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
Abciximab Facilitates ThrombolysisAbciximab Facilitates Thrombolysis tPA PhasetPA Phase
TIMI Frame Count- 60 min
P=0.001
0
20
40
60
80
100
00 2020 4040 6060 8080 100100
43
72
0
20
40
60
80
100P=0.0009
tPA 100 mg
TIMI 3 Flow- 60 min
tPA 50 mg + Abx
% P
ts
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
70 73 77
0
20
40
60
80
100
TIMI 3 Flow : 90 minTIMI 3 Flow : 90 minrPA PhaserPA Phase
10 + 10 U
87 88 75
5 + 5 U 10 + 5 U
% P
ts
N =
rPA rPA + Abx
rPA dose
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
TIMI 3 Flow : 90 minTIMI 3 Flow : 90 min tPA + tPA + rPA PhasesrPA Phases
627470 73
0
20
40
60
80
100
215 148 88
tPA50 mg
rPA5 + 5 U
% Pts
N =
Full Dose Lytic 50% Lytic+ Abx
87
tPA100 mg
rPA10 + 10 U
P=0.014
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
Determinants of TIMI 3 flow at 90 MinDeterminants of TIMI 3 flow at 90 MintPA + rPA pooledtPA + rPA pooled
0.2 1 5
TIMI 3 Flow (N=610)
LAD
Time (per hour)
Abciximab
More LikelyLess LikelyO.R.
O.R. (95 CI)
0.93 (0.88,0.99)
1.57 (1.09,2.26)P=0.01
0.73 (0.51,1.04)
Lytic
Non Significant
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
Evaluation of Myocardial PerfusionEvaluation of Myocardial Perfusion1. 1. ST Resolution:ST Resolution: Schr Schrööder JACC 26: 1657,1995der JACC 26: 1657,1995
CompleteComplete ( (>>70%) 70%) PartialPartial (30-70%) (30-70%) NoneNone ( (<< 30%) 30%)
2. 2. TIMI Myocardial Perfusion GradeTIMI Myocardial Perfusion Grade (MPG) (MPG)
CM Gibson Circulation 1999
TMP Grade 0 TMP Grade 1 TMP Grade 2 TMP Grade 3No or
minimal blushStain present.
Blush persists on next injection
Dye strongly persistent at end of washout. Gone by next injection
Normal ground glass appearance
of blush. Dye mildly persistent
at end of washout
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
Abciximab Improves Abciximab Improves Myocardial PerfusionMyocardial Perfusion
37
59
0
20
40
60
80
100
tPA tPA + Abx
% P
ts
Complete (> 70%) ST RES--90 min
P<0.001
N=125 N=221
42
60
0
20
40
60
80
100
rPA rPA + Abx
TMPG 2/390 min
P=0.08
N=33 N=66
de Lemos et al AHA 1999 C.M. Gibson 1999
tPA Phase rPA Phase
TIMI 14TIMI 14
Antman et al. Circ 99: 2720,1999
ConclusionsConclusionsReperfusion regimens to achieve TIMI 3 flow:Reperfusion regimens to achieve TIMI 3 flow:
1. Abciximab alone =1. Abciximab alone =full dose SK alonefull dose SK alone2. Abciximab augments 2. Abciximab augments rate and extent rate and extent ofof thrombolysis with thrombolysis with dose lytics dose lytics
60 min60 min 90 min90 min
tPA tPA tPA (50 mg)tPA (50 mg) tPA tPA tPA (50 mg)tPA (50 mg) 100mg 100mg + Abx + Abx 100mg 100mg + Abx+ Abx
TIMI 3 Flow 43% TIMI 3 Flow 43% 72%*72%* 62% 62% 77%*77%*
3. Safety profile encouraging3. Safety profile encouraging
Reperfusion regimens to achieve TIMI 3 flow:Reperfusion regimens to achieve TIMI 3 flow:1. Abciximab alone =1. Abciximab alone =full dose SK alonefull dose SK alone2. Abciximab augments 2. Abciximab augments rate and extent rate and extent ofof thrombolysis with thrombolysis with dose lytics dose lytics
60 min60 min 90 min90 min
tPA tPA tPA (50 mg)tPA (50 mg) tPA tPA tPA (50 mg)tPA (50 mg) 100mg 100mg + Abx + Abx 100mg 100mg + Abx+ Abx
TIMI 3 Flow 43% TIMI 3 Flow 43% 72%*72%* 62% 62% 77%*77%*
3. Safety profile encouraging3. Safety profile encouraging
* p=0.0009 unadjusted* p=0.0009 unadjusted* p=0.0009 unadjusted* p=0.0009 unadjusted * p=0.01 unadjusted* p=0.01 unadjusted* p=0.01 unadjusted* p=0.01 unadjusted