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BENEFITS OF CLOPIDOGREL IN PATIENTS UNDERGOING CORONARY STENTING SIGNIFICANTLY DEPEND ON LOADING DOSE: EVIDENCE FROM A SYSTEMATIC REVIEW AND META-REGRESSION. G. BIONDI-ZOCCAI 1 , C. MORETTI 1 , P. AGOSTONI 2 , M. VALGIMIGLI 3 , A. ABBATE 4 , D. ANGIOLILLO 5 ,
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BENEFITS OF CLOPIDOGREL IN PATIENTS UNDERGOING CORONARY STENTING SIGNIFICANTLY DEPEND ON LOADING DOSE: EVIDENCE FROM A SYSTEMATIC REVIEW AND META-REGRESSION 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
BACKGROUND • Clopidogrel is an established alternative to ticlopidine in addition to aspirin after coronary stenting because of its safety, but its optimal initial dosing is unclear • Moreover, there is ongoing uncertainty on the comparison of clopidogrel vs ticlopidine in terms of antithrombotic efficacy
OBJECTIVES • To perform a systematic review of randomized clinical trials (RCT) comparing clopidogrel vs ticlopidine • To pool major outcomes with meta-regression techniques focusing on clopidogrel front-loading
METHODS • PubMed was searched for pertinent studies (updated August 2006) • Random-effect odds ratios (OR) with 95% confidence intervals were computed for death or non-fatal myocardial infarction • Weighted least squares random-effect meta-regression was performed to explore the impact of loading vs non-loading clopidogrel scheme
RESULTS • We retrieved 7 trials (3382 patients, average follow-up 7 months) • In 5 studies both clopidogrel and ticlopidine were started with a loading dose, in 1 trial clopidogrel was administered without loading, and in 1 trial clopidogrel could be administered with or without loading • Overall analysis (p for heterogeneity=0.02) showed similar results for clopidogrel or ticlopidine (OR=0.90 [0.44-1.84], p=0.77)
RESULTS • In studies administering clopidogrel with loading, this treatment was however significantly better than ticlopidine (OR=0.60 [0.36-0.99], p=0.05) • This significant interaction between clopidogrel loading and its superiority in comparison to ticlopidine, was also formally confirmed by meta-regression (beta=-0.64, p=0.012)
CONCLUSIONS • The present updated systematic review and meta-regression of clinical trials comparing clopidogrel vs ticlopidine in patients undergoing coronary stenting shows that clopidogrel is superior to ticlopidine if an initial loading is administered • Conversely the available data suggest that clopidogrel might be inferior to ticlopidine if administered without loading
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