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Am Heart J. 2007 Apr;153(4):587-93.

Benefits of clopidogrel in patients undergoing coronary stenting significantly depend on loading dose: evidence from a meta-regression.

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Interventional Cardiology, Division of Cardiology, University of Turin, Turin, Italy.



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. We performed a systematic review and meta-regression of randomized clinical trials comparing clopidogrel versus ticlopidine, focusing on clopidogrel front-loading.


PubMed was searched for pertinent studies (updated August 2006). Random-effect odds ratios (ORs) with 95% CIs were computed for death or nonfatal myocardial infarction, and weighted least squares random-effect meta-regression was performed to explore the impact of loading versus nonloading clopidogrel scheme.


We retrieved 7 trials (3382 patients, average follow-up of 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 = .02) showed similar results for clopidogrel and ticlopidine (OR 0.90, 95% CI 0.44-1.84, P = .77). In studies administering clopidogrel with loading, this treatment was, however, significantly better than ticlopidine (OR 0.60, 95% CI 0.36-0.99, P = .05). This significant interaction between clopidogrel loading and its superiority in comparison with ticlopidine was also formally confirmed by meta-regression (beta = -0.64, P = .012).


This work supports the superiority of a clopidogrel regimen including an initial loading dose in comparison with ticlopidine in patients undergoing coronary stenting.

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