BENEFITS OF CLOPIDOGREL IN PATIENTS UNDERGOING CORONARY STENTING SIGNIFICANTLY DEPEND ON LOADING DOSE: EVIDENCE FROM A SYSTEMATIC REVIEW AND META-REGRESSION.

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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)

REVIEW PROFILE

INCLUDED STUDIES

RISK OF DEATH OR MI AT LONG-TERM FOLLOW-UP

META-REGRESSION

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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