iv heparin, (asa), beta-blockers, nitrates, ca ++ blockers
DESCRIPTION
TIMI IIIA. Protocol Design. 391 Patients with Unstable Angina / NQWMI. IV Heparin, (ASA), Beta-blockers, Nitrates, Ca ++ blockers. Angio Exclusion: no CAD or LMain. Baseline Angio. Randomize. Placebo. t-PA 0.8 mg/kg over 90 mins. Primary Endpoint: Death, MI, Positive ETT 6 weeks. - PowerPoint PPT PresentationTRANSCRIPT
IV Heparin, (ASA), Beta-blockers, Nitrates, Ca++ blockers
Randomize
Angio 18-36 hrs
t-PA0.8 mg/kg over 90 mins
391 Patients with Unstable Angina / NQWMI391 Patients with Unstable Angina / NQWMI
Placebo
Primary Endpoint:Death, MI,Positive ETT 6 weeks Follow-up 6 weeks Circulation 1993;87:38-52
Baseline AngioAngio Exclusion: no CAD or LMain
TIMI IIIATIMI IIIA Protocol Design
Apparent thrombus35%
Possible thrombus30%
No thrombus35%
Improvement in Culprit Lesion: 25% t-PA vs. 19% placebo p=NS
TIMI IIIA Investigators. Circulation 1993;87:38-52.
TIMI IIIATIMI IIIAEffects 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 / NQWMI1473 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 yearCirculation 1994;89:1545-56
2x2 Factorial:2x2 Factorial:t-PA vs. Placebot-PA vs. Placebo
1o Endpoint t-PA:Death, MI, Rec Isch,+ ETT, Thallium or ST Holter
TIMI IIIBTIMI IIIB Protocol Design
TIMI IIIB Investigators. Circulation 1994;89:1545-56
TIMI IIIBTIMI IIIB
tPA vs. Placebo in Non-ST Elevation ACSPrimary Results
54.2 55.5
0
10
20
30
40
50
60
70
80
tPA Placebo
8.8
6.2
0
2
4
6
8
10
12
tPA Placebo
0.55
00
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
tPA Placebo
Composite Endpoint Death or MI ICH
% o
f P
atie
nts
P = NS P = 0.05 P = 0.05
Events at 42dEvents at 42d InvasiveInvasive ConservativeConservative pp valuevalueNo. Pts 740 733Death (%) 2.4 2.5 NSMI (%) 5.1 5.7 NSD/MI/+ETT (%) 16.2 18.1 NS
Rehosp Angina (%) 7.8 14.1 <0.001D/MI/Rehosp (%) 15 22 0.007LOS (days) 10.2 10.9 <0.001# Days rehosp 365 930 <0.001
TIMI IIIB Investigators. Circulation 1994;89:1545-56
TIMI IIIBTIMI 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 IIITIMI III RREGISTRYEGISTRY Protocol Design
2.6 3.6
11
0.8
6.6
22.9
1.63.7
6.8
1.63.7
8.2
In-Hospital 6 Weeks 1 Year0
5
10
15
20
25
% o
f P
ati e
nts
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 IIITIMI III RREGISTRYEGISTRY
Admission ECG as a prognostic indicator
Risk Stratification
Death or MI
Antman et al. NEJM 1996; 335:1342-9
0 1 2 3 4 5
No CKMB Elev
All Patients
No CKMB Elev
All Patients
No CKMB Elev
All Patients
Mortality at 42 Days (%)
TnI < 0.4 ng/mlTnI > 0.4 ng/ml
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 IIIBTIMI IIIBcTnI to Predict Risk of Mortality in ACS
Risk Stratification