What's new about clopidogrel

Clopidogrel is an oral tyenopiridin with a central role in the management of acute coronary syndromes and after stent implantation. Despite the use of this drug, many patients continue to experience thrombotic events which are usually referred as "therapy failure". Actually, to date, only stent thrombosis is considered therapy failure: mainly, it could be due to patient genetic predisposition or drug interaction, in particular with proton pump inhibitors. Genetic mutations in the CYP2C19 cytochrome (involved in the metabolism of clopidogrel and many other drugs) may lead to a lower concentration of active metabolites of the drug. In the same way, proton pump inhibitors interaction with the cytochrome may reduce clopidogrel activation. To overcome the problem some authors have suggested to increase the dosage of the drug, to use other drugs, to genotype patients, and not to use proton pomp inhibitors in patients on double antiplatelet therapy. Recent studies have shown that the interaction between clopidogrel and proton pump inhibitors is far to be clinically relevant and that the variability between the different assay to determine patients response to the drug does not allow, to date, to rely on their use. Moreover, double clopidogrel dose is as effective as low one in preventing major cardiovascular events, with a significant reduction in stent thrombosis in spite of a modest increase in major bleeding. Aim of this review article was to update current knowledge on clopidogrel, particularly focusing on the problem of "resistance" and PPI interaction. Moreover, we will discuss current strategies to overcome the resistance.