UA NonST MI

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CURE and PCI-CURE
Keith A A Fox
Royal Infirmary University of Edinburgh
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Total outcomes admission to 6 months
Largest multinational registry covering the full
spectrum of ACS
ESC 2001
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Study Design

• Randomized, double-blind trial clopidogrel vs
  placebo in patients with ACS
• All patients receive ASA (75-325 mg)
• International trial (28 countries), 12,562
  patients
• Central randomization
• Primary outcome -CV death, MI, strokes

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CURE Study
300mg loadingdose
Clopidogrel75mg o.d.(6,250 patients)
Patients with Acute CoronarySyndrome
Aspirin 75-325mg
R
3 months gt double-blind treatment lt 12 months
(UA or MI Without STelevation)
Aspirin 75-325mg
Placebo 1 tab o.d.(6,250 patients)
Day 1
loading dose
6 m. Visit
9 m. Visit
3 m. Visit
1 m. Visit
12 m.or Final Visit
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Outcome Definitions
CV Death Excludes clear non-CV deaths

MI
Two of three standard criteria


(Chest Pain, ECG, enzyme
changes) Stroke Neurological deficit ? 24 hrs
(CT/MRI)
Refractory Ischemia Inhosp recurrent ischemia
on max med



Rx
ECG changes intervention ? 1 day After
discharge Rehosp for UA with ECG changes Severe
Ischemia Changes similar to RFA, but no
intervention Recurrent Angina All other
ischemic CP in hospital
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Cumulative Hazard Rates for CV Death/MI/Stroke
P 0.00005
6303
6259
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Cumulative Hazard Rates for CV Death/MI/Stroke up
to 30 Days
Placebo
Cumulative Hazard Rates
Clopidogrel
P0.003
0
10
20
30
Days of Follow-up
6303 6259
6097 6093
5994 6027
5954 5981
No. Plac No. Clop
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Very Early Events
plt0.05 lt0.01 lt0.002
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Events During Initial Hospitalization
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CURE Who Benefits and When?

• Similar benefits across all major treatment
  groups
• On or off lipid lowering treatment,
  beta-blockers, heparin, ACE inhibitors
• Irrespective of revascularization or not
• RR 0.81 with and RR 0.78 without, both
  significant
• Higher and lower risk groups show similar risk
  reduction
• Curves separate early and remain separated
• Primary outcome at 24hrs
• 143 vs 93 clopidogrel (RR 0.65 CI 0.50 0.85)

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Life Threatening Bleed
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Bleeds With CABG
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CURE Magnitude of Benefit

• Primary Outcome
• MI, stroke or CV death 11.4 placebo,
• 9.2 clopidogrel (22 per 1000 absolute
  difference)
• (Non-CV death 0.7 vs 0.7)

Treating 1000 patients for 9 months prevents 28
vascular events with 6 individuals requiring
transfusion
TIMI bleeding criteria 68 clopidogrel,73 placebo
RR 0.94 (CI 0.68-1.30) GUSTO criteria 78
clopidogrel, 70 placebo RR 1.11 (CI 0.81-1.55)
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Study Design
CURE
PCI-CURE
N2,658 patients undergoing PCI
Pretreatment
Open-label thienopyridine
PLACEBO ASA
N 1345
End of follow-up 12 months
30 d. post PCI
PCI
Randomize
Open-label thienopyridine
CLOPIDOGREL ASA
N 1313
Pretreatment
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Baseline Characteristics
Clopidogrel n1254
Placebo n1272
61.6
61.4
Age (yrs)
30.3
30.1
Sex (F)
19.0
19.0
Diabetes
27.3
26.0
Previous MI
13.4
13.8
Prior PCI
12.0
13.0
Prior CABG
43.2
ST depression
42.4
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Overall Results CV Death or MI
0.15
Placebo
0.10
Clopidogrel
Cumulative Hazard Rate
0.05
P0.002
0.0
0
40
100
200
300
400
10
100
200
300
400
Amedian time to PCI B30 days after PCI
A
B
Days following PCI
Lancet 2001 358527-33
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Events Before PCI
Lancet 2001 358527-33
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Major Outcomes From PCI to 30 days
Primary endpoint
Lancet 2001 358527-33
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Other Outcomes
Mehta SR et. al. Lancet 2001 358527-33
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Major Outcomes Long Term Treatment
Lancet 2001 358527-33
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Clinical Suspicion of ACS Physical examination,
ECG Blood samples
No persistent STelevation
Aspirin b-blocker heparin clopidogrel