CURE: Clopidogrel in Unstable angina to prevent Recurrent Events
Purpose
To determine the efficacy and safety of the antiplatelet agent clopidogrel plus early and long-term aspirin, compared with aspirin alone, in patients with acute coronary syndromes
Reference
The CURE Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494–502.
CURE: Clopidogrel in Unstable angina to prevent Recurrent Events - TRIAL DESIGN -
Design
Multicenter, multinational, randomized, double-blind, placebo-controlled
Patients
12,562 patients hospitalized within 24h of onset of symptoms of an acute coronary syndrome, without ST-segment elevation; patients at risk for bleeding or severe heart failure excluded
Follow up and primary endpoint
Primary combined endpoint: death from cardiovascular causes, nonfatal MI or stroke. Follow up 3–12 months
Treatment
Aspirin 75–325 mg daily, plus either placebo or clopidogrel 300 mg loading dose then 75 mg daily
CURE: Clopidogrel in Unstable angina to prevent Recurrent Events - RESULTS -
Clopidogrel, compared with placebo, gave significant reduction in:
first primary outcome: a composite of death from cardiovascular causes, nonfatal MI or stroke (9.3 vs. 11.4%, relative risk 0.80, P<0.001)
composite of first primary outcome or refractory ischemia (16.5 vs. 18.8%, relative risk P<0.001)
Rate of each outcome component tended to be lower in clopidogrel group, however clearest difference was in rate of MI
Clopidogrel group had significantly higher rate of major and minor bleeding (both P<0.001) but life-threatening bleeding was not significantly different from placebo
Drug well tolerated as defined by lack of excess rate of any other adverse event necessitating withdrawal
CURE: Clopidogrel in Unstable angina to prevent Recurrent Events - RESULTS continued -
Months after randomization
Cumulative
hazard rate
0
0.00
3
6
9
12
0.14
0.12
0.10
0.08
0.06
0.04
0.02
First primary outcome:
death from cardiovascular causes, nonfatal MI or stroke
Placebo
Clopidogrel
The CURE Trial Investigators. N Engl J Med 2001; 345:494–502.
P <0.001
CURE: Clopidogrel in Unstable angina to prevent Recurrent Events - RESULTS continued -
P
First primary outcome:
death from cardiovascular causes,
Second primary outcome:
first primary outcome or refractory
ischemia
Death from cardiovascular causes
MI
Death from noncardiovascular
causes
0.80 (0.72
–
0.90)
0.86 (0.79
–
0.94)
0.93 (0.79
–
1.08)
0.77 (0.67
–
0.89)
0.91 (0.60
–
1.39)
<0.001
<0.001
Main study outcomes
Placebo
(n=6303)
No. (%)
Clopidogrel
(n=6259)
No. (%)
The CURE Trial Investigators. N Engl J Med 2001; 345:494–502.
582 (9.3)
1035 (16.5)
318 (5.1)
324 (5.2)
41 (0.7)
719 (11.4)
1187 (18.8)
345 (5.5)
419 (6.7)
45 (0.7)
Relative risk
(95% CI)
nonfatal MI or stroke
CURE: Clopidogrel in Unstable angina to prevent Recurrent Events - RESULTS continued -
P
Bleeding complications
Placebo
(n=6303)
No. (%)
Clopidogrel
(n=6259)
No. (%)
The CURE Trial Investigators. N Engl J Med 2001; 345:494–502.
Relative risk
(95% CI)
CURE: Clopidogrel in Unstable angina to prevent Recurrent Events - SUMMARY -
In patients with acute coronary syndromes, addition of clopidogrel to early and long-term aspirin:
Reduced a composite of death from cardiovascular causes, non-fatal MI, or stroke; also reduced a composite of these or refractory ischemia
Increased major and minor bleeding complications