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

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. We performed a systematic review and meta-regression of randomized clinical trials comparing clopidogrel versus ticlopidine, focusing on clopidogrel front-loading. Methods 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. Results 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 (β = −0.64, P = .012). Conclusions This work supports the superiority of a clopidogrel regimen including an initial loading dose in comparison with ticlopidine in patients undergoing coronary stenting.