Transcript cureresults - Clinical Trial Results

CURE: Design Issues
• 12, 562 patients enrolled in 28 countries
• Europe enrolled 5,000; Canada enrolled 2,000; the
US enrolled 500
• Male: 61%
• Unstable angina 75%
• EKG abnormal 93%
• Elevated troponin 25%
• Heparin 46%
• LMWH 50%
• Beta blocker 78%
• Lipid lowering 47%
S Yusuf, Am Coll Cardiol 2001
CURE: Design Issues
12,562 pts.
Randomized to either
ASA 75 to 325 mg
ASA + Clopidogrel
PO qd
(300 mg load, 75 mg qd)
3 to 12 month follow-up
Average 9 months
S Yusuf, Am Coll Cardiol 2001
CURE: Primary Endpoint Results
Risk Ratio 0.80
p=0.00005
11.47%
9.28%
10
8
There was a 20%
reduction in the primary
endpoint of the study
6
4
2
N = 6,303
N = 6,259
Aspirin
Aspirin +
0
Clopidogrel
S Yusuf, Am Coll Cardiol 2001
CURE: Subgroup Results
MI (%)
4
4
3
3
2
0
0
ASA +
Clopidogrel
1
ASA +
Clopidogrel
1
ASA
2
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
1.4%
1.2%
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0.7%
0.67%
Clopidogrel
5
5.19%
Control
6.68%
Non CV Death (%)
5
6
ASA
5.06%
P = NS
P = NS
Risk of Stroke (%)
5.4%
ASA
CV Death (%)
6
P < 0.001
ASA +
Clopidogrel
P = NS
S Yusuf, Am Coll Cardiol 2001
CURE: Other efficacy results
Aspirin
(n=6303)
Aspirin +
clopidogrel
(n=6259)
19.02%
16.68%
0.88
Refractory ischemia
9.4%
8.8%
0.93
N/A
Refractory ischemia
in hospital
2.08%
1.42%
0.69
Significant
Refractory
ischemia after
discharge
7.66%
7.67%
1.00
N/A
Severe
ischemia
5.03%
3.83%
Endpoint
CV death, MI, stroke
, refractory ischemia
(2nd primary
endpoint)
Relative
risk
0.76
p value
0.0004
0.001
S Yusuf, Am Coll Cardiol 2001
CURE: Bleeding Results
Endpoint
Aspirin
(n=6303)
Aspirin +
clopidogrel
(n=6259)
Relative
risk
p value
Major bleeding
2.7%
3.6%
1.34
0.003
Life-threatening
bleeding
1.8%
2.1%
1.15
N/A
Minor bleeding
8.6%
15.3%
1.78
<0.001
2.2%
2.8%
1.28
0.03
Transfusions
S Yusuf, Am Coll Cardiol 2001
CURE: High-risk/low-risk subgroup
analysis: primary endpoint
Endpoint
ST changes
Aspirin
(n=6303)
Aspirin + clopidogrel
(n=6259)
Risk ratio
14.3%
11.5%
0.79
8.7%
7.0%
0.80
13.1%
10.7%
0.81
No enzyme
elevations
10.9%
8.8%
0.79
Previous
revascularizations
14.6%
8.4%
0.55
No previous
revascularizations
10.8%
9.5%
0.87
Postrandimization
revascularizations
1.39%
11.4%
0.81
No
postrandimization
revascularizations
10.1%
8.4%
0.79
No ST changes
Enzyme elevations
S Yusuf, Am Coll Cardiol 2001
CURE: Results in Context
• Potential Magnitude of Benefit
– 2 million hospitalizations each year for ACS in US
alone
– “50,000 to 100,000 deaths, MIs and strokes could be
prevented each year in North America alone” (S. Yusuf,
P.I.)
– 250,000 to 500,000 major events prevented worldwide
even if only 20% of eligible patients are treated
• Potential Obstacles to Benefit
– Cost of $2.00 to $3.00 per day per pill, not covered by
Medicare outpatient costs (inpatient costs of the drug
would be covered)
S Yusuf, Am Coll Cardiol 2001
CURE: Future Studies
• There are 12 million patients with stable CAD in the US
and it is unclear if these patients would benefit from the
drug and this will require further study
S Yusuf, Am Coll Cardiol 2001