A Review of Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic

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A Review of Clopidogrel and Aspirin versus
Aspirin Alone for the Prevention of
Atherothrombotic

• Ted Williams
• Pharm D Candidate
• Monday Lab

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Study Objective

• Determine if Clopidogrel ASA 81mg decreases
  risk of CV Events vs. ASA 81mg alone.
• Null Hypothesis
• Clopidogrel ASA 81mg no different than ASA 81mg
  alone in reducing CV Events
• Alternative Hypothesis
• Clopidogrel ASA 81mg is superior to ASA 81mg
  alone in reducing CV Events

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Methods

• Study Design
• Multicenter, randomized, double-blind,
  placebo-controlled (n15,603)
• Executed by Cleveland Clinic Cardiovascular
  Coordination Center
• Sponsored by Sanofi-Aventis Bristol-Myers
  (Plavix Patent holder)
• Safety and Efficacy endpoints
• Plavix ASA 81mg vs. Placebo ASA 81mg
• Methods - Inclusions
• gt45yrs
• Established CVD
• Multiple risk factors for CVD
• DM
• Diabetic Nephropathy
• Ankle-Brachial index lt0.9
• Carotid Stenosis
• Carotid Plaque

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Methods - Analysis

• Efficacy
• Primary end point of MI, Stroke, or Death due to
  CV event/hemorrhage
• Secondary endpoint incidence of CV events or
  hospitalization for CAD related events
• 20 Relative Risk Reduction detectable based on
  power
• 2 sided log-rank test
• Intent to treat
• Non-cardiovascular death excluded from Efficacy
  endpoint
• Safety
• Pearson chi-square test

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Efficacy Findings
Clopidogrel and Aspirin versus Aspirin Alone for
the Prevention of Atherothrombotic Events. (NEJM
20073541706-17)
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Subgroup Analysis

• No significant efficacy difference in any subgroup

Clopidogrel and Aspirin versus Aspirin Alone for
the Prevention of Atherothrombotic Events. (NEJM
20073541706-17)
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Safety Findings

• Moderate Bleeding significantly increased

Clopidogrel and Aspirin versus Aspirin Alone for
the Prevention of Atherothrombotic Events. (NEJM
20073541706-17)
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Areas for Future Study

• Symptomatic vs Asymptomatic Patients?
• Platelet abnormalities?

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Hypothesis Testing

• Null Hypothesis
• Clopidogrel ASA 81mg no different than ASA 81mg
  alone in reducing CV Events
• Failed to Reject
• Alternative Hypothesis
• Clopidogrel ASA 81mg is superior to ASA 81mg
  alone in reducing CV Events
• Rejected

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Conclusions

• Dual ASA and Clopidogrel therapy is not generally
  indicated to prevent CV events
• Moderate Bleeding is the area of risk
• Future research should be conducted to determine
  potential benefits in patients with establish CV
  disease

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References

• Bhatt, B., Fox, D., Hacke, W., et al, (2007)
  Clopidogrel and Aspirin versus Aspirin Alone for
  the Prevention of Atherothrombotic Events. NEJM
  20073541706-17. Retrieved from
  http//content.nejm.org/cgi/content/full/354/16/17
  06 on 01/21/2007