IV Heparin, (ASA), Beta-blockers, Nitrates, Ca++ blockers
Randomize
Angio 18-36 hrs
t-PA
0.8 mg/kg over 90 mins
391 Patients with Unstable Angina / NQWMI
Placebo
Primary Endpoint:
Death, MI,
Positive ETT 6 weeks
Follow-up 6 weeks
Circulation 1993;87:38-52
Baseline Angio
Angio Exclusion:
no CAD or LMain
TIMI IIIA
Protocol Design
Apparent thrombus
35%
Possible thrombus
30%
No thrombus
35%
Improvement in Culprit Lesion: 25% t-PA vs. 19% placebo p=NS
TIMI IIIA Investigators. Circulation 1993;87:38-52.
TIMI IIIA
Effects of tPA on Coronary Lesions
Primary Results
BASELINE ANGIORAPHY:
ANGIORAPHY AFTER tPA:
ASA, IV Heparin, Beta-blockers, Nitrates, Ca++ blockers
Randomize
ETT 6 weeks
Early Invasive:
Cath 18-48 h
PTCA/CABG prn
1473 Patients with Unstable Angina / NQWMI
Early Conservative:
ST Holter, ETT Thallium
Cath/PTCA if +ischemia
1o Endpoint Inv-Cons:
Death, MI,
Positive ETT - 6 weeks
Follow-up 1 year
Circulation 1994;89:1545-56
2x2 Factorial:
t-PA vs. Placebo
1o Endpoint t-PA:
Death, MI, Rec Isch,
+ ETT, Thallium
or ST Holter
TIMI IIIB
Protocol Design
TIMI IIIB Investigators. Circulation 1994;89:1545-56
TIMI IIIB
tPA vs. Placebo in Non-ST Elevation ACS
Primary Results
Composite Endpoint
Death or MI
ICH
% of Patients
P = NS
P = 0.05
P = 0.05
Events at 42d Invasive Conservative p value
No. Pts 740 733
Death (%) 2.4 2.5 NS
MI (%) 5.1 5.7 NS
D/MI/+ETT (%) 16.2 18.1 NS
Rehosp Angina (%) 7.8 14.1 <0.001
D/MI/Rehosp (%) 15 22 0.007
LOS (days) 10.2 10.9 <0.001
# Days rehosp 365 930 <0.001
TIMI IIIB Investigators. Circulation 1994;89:1545-56
TIMI IIIB
Early Invasive vs. Conservative Strategy
Primary Results
All consecutive patients admitted with unstable angina were screened.
Inclusion Criteria: Ischemic pain >5 mins within 96 hrs with unstable pattern: At rest, accelerating, post MI
Exclusion Criteria: Non-ischemic pain, ST elevation, admitted for revascularization procedure
Patients in specific subgroups defined by gender, race and age were randomly selected for detailed evaluation and follow-up at 6 weeks and 1 year.
TIMI III REGISTRY
Protocol Design
2.6
3.6
11
0.8
6.6
22.9
1.6
3.7
6.8
1.6
3.7
8.2
In-Hospital
6 Weeks
1 Year
0
5
10
15
20
25
% of Patients
ST deviation >0.1 mV
LBBB
Tw change
No ECG changes
_
Stone PH, TIMI III Registry Study Group. JAMA 1996;275:1104-1112.
Cannon CP et al for ECG Substudy Investigators. JACC 1997;30:133-40.
TIMI III REGISTRY
Admission ECG as a prognostic indicator
Risk Stratification
Death or MI
Antman et al. NEJM 1996; 335:1342-9
Enrolled 0-6 hrs
Enrolled 6-24 hrs
Enrolled 0-24 hrs
P<0.001
P <0.05
P <0.05
P<0.001
TIMI IIIB
cTnI to Predict Risk of Mortality in ACS
Risk Stratification