Combination of Clopidogrel and Statins: A Hypothetical Interaction or Therapeutic Dilemma?

BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and clopidogrel are frequently used in the treatment of patients with various cardiovascular disorders. The possibility of a drug-drug interaction between certain statins and clopidogrel has been extensively investigated in the literature recently. Investigators have proposed that the use of statins that are metabolized by the cytochrome P450 (CYP) system may diminish the conversion of clopidogrel to its active form by inhibiting the CYP3A4 isoenzyme. This inhibition could result in a decreased antiplatelet effect of clopidogrel, which could translate into an increased risk of cardiovascular events. METHODS: We performed a MEDLINE search of the literature from 1993-2005 to evaluate and discuss the existing data on a possible interaction between clopidogrel and statins and to provide clinicians with relevant and practical recommendations. Additional studies were identified from the bibliographies of the reviewed literature. RESULTS: Several articles were discovered that discuss this potential drug-drug interaction. Whereas some studies indicated that there was not a relevant interaction between statins and clopidogrel, other studies demonstrated that the concomitant administration of some statins with clopidogrel resulted in diminished platelet inhibition activity of clopidogrel. CONCLUSIONS: Although the interaction between certain statins and clopidogrel seems to be a pharmacologic certainty, the clinical relevance of this interaction needs further clarification. While investigators continue to evaluate the clinical relevance, we provide several recommendations for clinicians responsible for treating patients who require combination therapy with statins and clopidogrel.