TACTICS- TIMI 18
Treat Angina with AggrastatTM
and Determine Cost of Therapy
with an
Invasive or Conservative Strategy
Unstable Angina and Non-Q Wave MI
Center of spectrum of acute coronary syndromes
2-2.5 million hospital admissions /year worldwide
ASA, heparin, beta-blockers beneficial
Tirofiban (AggrastatTM) dramatic benefit
Invasive vs. Consvative strategy ????
Background
Unstable angina and non-Q wave MI
Center of spectrum of acute coronary syndromes
890,000 hospital admissions per year in U.S.
ASA, heparin, beta-blockers beneficial
Tirofiban (AggrastatTM) dramatic benefit
Invasive vs. Consvative strategy ????
Background
Initial Medical Management:
ASA 160-325 mg daily for all patients with UA (except if ongoing major or life-threatening hemorrhage, recent GI bleed, or ASA hypersensitivity)
IV Heparin for intermediate or high-risk UA (i.e., prior CAD, rest pain, ECG changes, or age >65)
Beta-blockers for all patients in the absence of contraindications (e.g., bradycardia, hypotension, AV block, asthma, severe LV dysfunction with CHF or shock, signif. COPD)
Recommendations
AHCPR Unstable Angina Guideline
Braunwald, E., et al. Circulation 1994;90:613-22.
Initial Medical Management (con’t):
Nitrates: Use for patients with ongoing ischemia and use IV for high-risk patients. Switch to oral when stable
Calcium antagonists: May be used to control angina if already on beta-blocker and nitrates, or if unable to tolerate beta-blockers (e.g. severe COPD). Use heart-rate lowering Ca+ blocker. Avoid in CHF or low EF.
No thrombolysis: Shown to increase subsequent MI in TIMI IIIB trial in patients with unstable angina
Recommendations
AHCPR Unstable Angina Guideline
Braunwald, E., et al. Circulation 1994;90:613-22.
Cholesterol Lowering Post MI
4S
CARE
Cholesterol lowering: Check lipids <24 hours, treat as needed. CARE trial indicates benefit for patients with LDL >125 mg/dl.
Low Molecular Weight Heparin: At least as effective as IV heparin. ESSENCE trial: 16% better than IV heparin (Death, MI, recurrent angina)
IIb/IIIa inhibition: Tirofiban lead to a 34% reduction in death, MI, refarctory angina at 7 days in PRISM-PLUS. At 30 days, tirofiban (AggrastatTM) lead to a 31% redution in death or MI. In PRISM, there was a 36% reduction in composite endpoint at 48 hours. Eptifibatide (IntegrilinTM) lead to an 11% reduction in death or MI at 30 days in PURSUIT.
Updating - 1997
AHCPR Unstable Angina Guideline
Early invasive strategy - Cath in all patients between 18-48 hours. Revascularization when feasible based on anatomy: PTCA for 1 or 2 VD, CABG for 3VD
Early conservative strategy - catheterization if patient had recurrent ischemia at rest or on testing:
Recurrent ischemia at rest with ECG changes
Recurrent MI
Positive ETT / Thallium at HD or 6 weeks
Positive ST segment Holter (>20 mins)
Invasive vs. Conservative
TIMI IIIB
Circulation 1994;89:1545-56
TIMI IIIB - One Year Results
Death or MI
PTCA or CABG
P=<0.001
P=NS
Anderson HV et al., JACC 1995;26:1643-1650.
12.2%
10.8%
64%
58%
Early Conservative
Early Invasive
Early Invasive
Early Conservative
TIMI IIIB - Primary Results to 42 days
Invasive Conserv. 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
Circulation 1994;89:1545-56
VANQWISH Trial
VA Hosptials Study: Management post Non-Q wave MI
Medical and interventional magagement of unstable angina markedly improved in last 5 yrs ( ASA, heparin, stents, operator exper.)
Tirofiban improves:
Medical management of unstable angina (PRISM, PRISM-PLUS)
Outcome following PTCA (RESTORE)
With current optimal management Which is better and more cost-effective -> Invasive vs. Consvative strategy ?
Study Rationale
TIMI IIIB: Troponin I vs. 42 Day Mortality
0-<0.4
0.4-<1.0
1.0-<2.0
2.0-<5.0
5.0-<9.0
> 9.0
0
1
2
3
4
5
6
7
8
Death by 42 Days (%)
cTnI at Baseline (ng/ml)
1.0
1.7
3.4
3.7
6.0
7.5
Risk Ratio
6.2
7.8
3.5
3.9
1.0
1.8
831
174
148
134
50
67
C2 p<0.001
Antman et al. NEJM 1996;335: 1342-9.
Troponin T and I: associated with risk of death
TACTICS-TIMI 18 tests “Troponin Hypothesis” The troponins will be useful in determining the best treatment strategy (invasive vs. conservative)
Which is better - T or I?
TACTICS-TIMI 18 will be first large comparison
Additional Objectives
Troponin Hypothesis