1. A Review of – Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Ted Williams Pharm D Candidate Monday Lab

2. 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

3. Methods Study Design –Multicenter, randomized, double-blind, placebo-controlled (n=15,603) –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 –>45yrs –Established CVD –Multiple risk factors for CVD DM Diabetic Nephropathy Ankle-Brachial index <0.9 Carotid Stenosis Carotid Plaque

4. 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

5. Efficacy Findings Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events. (NEJM 2007;354:1706-17)

6. Subgroup Analysis No significant efficacy difference in any subgroup Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events. (NEJM 2007;354:1706-17)

7. Safety Findings Moderate Bleeding significantly increased Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events. (NEJM 2007;354:1706-17)

8. Areas for Future Study Symptomatic vs Asymptomatic Patients? Platelet abnormalities?

9. 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

10. 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

11. References Bhatt, B., Fox, D., Hacke, W., et al, (2007) Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events. NEJM 2007;354:1706-17. Retrieved from http://content.nejm.org/cgi/content/full/354/16/1706 on 01/21/2007http://content.nejm.org/cgi/content/full/354/16/1706