CYP1A2-inducing medications improve platelet responsiveness to clopidogrel

Key Points

Platelet response to clopidogrel (Plavix) may be enhanced by concomitant use of agents that induce cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2), according to research presented during the 39th annual meeting of the American College of Clinical Pharmacology, Baltimore.

Clopidogrel nonresponsiveness has been recorded in a significant number of patients. Interactions with concomitant drugs that affect the cytochrome P450 system may contribute to this nonresponsiveness.

"These are the first data to show that medications inducing CYP1A2 on clopidogrel are associated with a higher likelihood of platelet responsiveness to clopidogrel," noted lead author Francis M. Gengo, PharmD, FCP.

Of these patients, 115 (33%) were found to be partially responsive or nonresponsive. Concomitant medications taken by the patients were then categorized as substrates, inhibitors, or inductors of CYP3A4, 2C9, 2C19, 2B6, 1A2, and 3A5.

Using step-wise forward and backward logistic regression analysis, researchers found that patients prescribed CYP1A2 inducers concomitantly were significantly more likely to be responsive to clopidogrel (OR, .575; P<.05). In addition, female gender increased the odds of being nonresponsive (OR, 2.04; P=.004), as did diabetes (OR, 1.95; P=.019).

These researchers then used step-wise forward and backward logistic regression analysis to assess the statistical significance of the effects of major, moderate, or minor CYP1A2 inducers taken concomitantly. Classification and regression tree (CART) analysis was used to assess the significance on the number of CYP1A2 inducers each patient was taking. Neither the strength nor the number of CYP1A2 inducers affected patient responsiveness, noted Dr Gengo, who is with the department of neurology, University at Buffalo, and DENT Neurologic Institute, Amherst, NY.

"Significant demographical risk factors that increased the odds ratio for being nonresponsive to clopidogrel included female gender and diabetes," said Dr Gengo. "While interactions with drugs affecting other CYP isoenzymes were not detected, likely because of the greater genetic variation in the expression of these enzymes, CYP1A2 inducers were shown to significantly affect clopidogrel responsiveness. However, neither number nor strength of inducers was implicated in the effect, likely because of the small sample size available," he concluded.