CURE: Clopidogrel in Unstable angina to prevent Recurrent Events

1
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 2001345494502.

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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 312 months
• Treatment
• Aspirin 75325 mg daily, plus either placebo or
  clopidogrel 300 mg loading dose then 75 mg daily

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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, Plt0.001)
• composite of first primary outcome or refractory
  ischemia (16.5 vs. 18.8, relative risk Plt0.001)
• 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 Plt0.001) 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

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CURE Clopidogrel in Unstable angina to prevent
Recurrent Events- RESULTS continued -
First primary outcome
death from cardiovascular causes, nonfatal MI or
stroke
Cumulative
0.14
hazard rate
0.12
0.10
0.08
0.06
0.04
Placebo
0.02
Clopidogrel
P lt0.001
0.00
0
3
6
9
12
Months after randomization
The CURE Trial Investigators. N Engl J Med 2001
345494502.

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CURE Clopidogrel in Unstable angina to prevent
Recurrent Events- RESULTS continued -
Main study outcomes
Placebo
Clopidogrel
Relative risk
P
(n6303)
(n6259)
(95 CI)
No. ()
No. ()
lt0.001
First primary outcome
0.80 (0.72

0.90)
582 (9.3)
719 (11.4)

death from cardiovascular causes,



nonfatal MI or stroke




lt0.001
Second primary outcome
0.86 (0.79

0.94)
1035 (16.5)
1187 (18.8)
first primary outcome or refractory



ischemia



Death from cardiovascular causes
0.93 (0.79

1.08)
318 (5.1)
345 (5.5)
MI
0.77 (0.67

0.89)
324 (5.2)
419 (6.7)
Death from noncardiovascular
0.91 (0.60

1.39)
41 (0.7)
45 (0.7)
causes
The CURE Trial Investigators. N Engl J Med 2001
345494502.
6
CURE Clopidogrel in Unstable angina to prevent
Recurrent Events- RESULTS continued -
Bleeding complications
Placebo
Clopidogrel
Relative risk
P
(n6303)
(n6259)
(95 CI)
No. ()
No. ()





The CURE Trial Investigators. N Engl J Med 2001
345494502.
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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