Non-bleeding side effects of clopidogrel: have large multi-center clinical trials underestimated their incidence?

Large multi-center clinical trials have indicated significant clinical benefits for patients with atherosclerotic vascular diseases receiving clopidogrel therapy. Clopidogrel efficacy has been proven in cardiac and extracardiac vascular diseases. Thus, the popularity of using clopidogrel is likely to increase in the near future. However, clopidogrel therapy may be accompanied by rare life-threatening adverse events. An increasing body of evidence show that clopidogrel is associated with aplastic anemia, thrombocytopenia and neutropenia. Interestingly, the majority of multi-center clinical trials have reported bleeding as the major side effect of clopidogrel therapy and failed to detect the actual incidence of other serious hematological side effects. Highlighting the potential adverse events of clopidogrel therapy in large clinical trials is therefore essential if we are to learn any lessons from having ignored the reporting of serious adverse side effects of a closely related drug (ticlopidine) in its large clinical trials.