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Genotyping prior to clopidogrel treatment?

Clopidogrel, which is used as a platelet aggregation inhibitor for the prophylaxis of atherothrombotic complications, is enzymatically activated by the enzyme CYP2C19. Patients whose genetic predisposition prevents or reduces the production of this enzyme could therefore benefit less from clopidogrel treatment. These patients might be better treated with an alternative antithrombotic agent. Recent research found evidence that it might be useful to determine a patient’s genetic predisposition for CYP2C19 (genotyping) prior to percutaneous coronary intervention (PCI) immediately after a cardiac infarction. Patients who were given this treatment based on genotyping had a reduced risk of minor haemorrhages compared to patients given the treatment of first choice without genotyping. For the indications of elective PCI (without cardiac infarction) or stroke, there is no convincing evidence that adapting the treatment to the CYP2C19 genotype offers any added value. Hence, doctors should be reticent about the routine use of prior genotyping for these indications.

  • Current therapeutic guidelines do not offer unequivocal advice on the need for CYP2C19 genotyping prior to antithrombotic treatment with clopidogrel. 
  • For patients who are to be treated with percutaneous coronary intervention (PCI) following a cardiac infarction, CYP2C19 genotyping appears to reduce the risk of minor haemorrhages compared to the current routine antithrombotic treatment with ticagrelor or prasugrel. 
  • For patients undergoing PCI for stable coronary vascular disease or for patients with a stroke, there is no evidence from randomised studies for an added value of CYP2C19 genotyping prior to treatment with clopidogrel.
  • Until the indication for clopidogrel is included in prescription and pharmacy systems it seems too early to include genotyping for clopidogrel as a standard advisory signal in these systems.

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  • Sander van den Bogert, dr, pharmacist