1. 1 SUPERIORITY OF A HIGH CLOPIDOGREL LOADING DOSE REGIMEN IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: EVIDENCE FROM A META-ANALYSIS G. BIONDI-ZOCCAI1, C. MORETTI1, P. AGOSTONI2, M. VALGIMIGLI3, A. ABBATE4, D. ANGIOLILLO5, G. SANGIORGI6, G. TREVI1 AND I. SHEIBAN1 1University of Turin, Turin, Italy; 2AZ Middelheim, Antwerp, Belgium; 3University of Ferrara, Ferrara, Italy; 4Virginia Commonwealth University, Virginia, USA; 5University of Florida, Jacksonville, Florida, USA; 6Emo Centro Cuore Columbus, Milano, Italy gbiondizoccai@gmail.comgbiondizoccai@gmail.com – http://www.comet.gshttp://www.comet.gs

2. 2 DISCLOSURE Dr. Biondi-Zoccai has received lecture fees from Bristol Myers Squibb

3. 3 BACKGROUND In patients undergoing intracoronary stenting, adjunctive treatment with clopidogrel in addition to aspirin is pivotal to minimize thrombotic occlusions and peri-procedural adverse events High loading dose regimens of clopidogrel (600 mg or more) lead to faster and enhanced platelet inhibition compared to standard dosing (300 mg) and may translate into improved clinical outcomes However, the clinical impact of high clopidogrel front- loading derives from small size trials and to date which is the best clopidogrel loading dose regimen is still a topic of debate

4. 4 OBJECTIVES To perform a systematic review to identify the optimal clopidogrel loading dose regimen in patients scheduled for coronary angiography and/or intervention To pool major outcomes with meta- analytic techniques

5. 5 METHODS Pertinent controlled trials were systematically searched in PubMed and other databases Authors of pertinent studies were systematically contacted The end-points were the rate of in-hospital myocardial infarction, and the 1-month rate of death or myocardial infarction Fixed-effect odds ratios (OR), 95% confidence intervals and p values were computed

6. 6 RESULTS A total of 10 studies (7 randomized, 3 non- randomized) were included, enrolling 1567 patients (712 loaded with 300 mg, 11 with 450 mg, 790 with 600 mg, and 54 with 900 mg) Overall a high loading dose proved significantly superior to a standard loading in preventing in- hospital myocardial infarction (OR=0.51 [0.26- 0.99], p=0.05) and in preventing cardiac death or non-fatal myocardial infarction (OR=0.50 [0.30-0.84], p=0.009)

7. 7 RESULTS No significant increase in major or minor bleedings (respectively p=0.55 and p=0.98) was found in patients treated with a high clopidogrel dose Sensitivity analysis restricted to randomized trials confirmed the superiority of a high loading dose regimen on risk of death or infarction (p=0.001) Meta-regression disclosed a significant interaction between event rate and benefits of high loading dose (p=0.005), suggesting that the higher the underlying risk, the greater the favorable impact of high loading

8. 8 REVIEW PROFILE

9. 9 INCLUDED STUDIES

10. 10 RISK OF D/MI AT 1 MONTH

11. 11 META-REGRESSION

12. 12 FUNNEL PLOT

13. 13 CONCLUSIONS Despite the inherent limitations of available evidence, a high clopidogrel loading dose regimen appears clinically and statistically superior to a standard (ie 300 mg) loading dose regimen in preventing coronary ischemic events Moreover, the greatest benefits can be expected in the highest risk subjects