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G. BIONDI-ZOCCAI 1 , C. MORETTI 1 , P. AGOSTONI 2 ,

SUPERIORITY OF A HIGH CLOPIDOGREL LOADING DOSE REGIMEN IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: EVIDENCE FROM A META-ANALYSIS. G. BIONDI-ZOCCAI 1 , C. MORETTI 1 , P. AGOSTONI 2 , M. VALGIMIGLI 3 , A. ABBATE 4 , D. ANGIOLILLO 5 , G. SANGIORGI 6 , G. TREVI 1 AND I. SHEIBAN 1

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G. BIONDI-ZOCCAI 1 , C. MORETTI 1 , P. AGOSTONI 2 ,

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  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.com – http://www.comet.gs

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

  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. 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. 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. 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. 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. REVIEW PROFILE

  9. INCLUDED STUDIES

  10. RISK OF D/MI AT 1 MONTH

  11. META-REGRESSION

  12. FUNNEL PLOT

  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

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