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CYP2C19-genotyping for clopidogrel after percutaneous coronary intervention (PCI)

No evidence for usefulness of routine assessment


For patients with a fully or partially inactive CYP2C19 enzyme, treatment with ticagrelor or prasugrel for up 12 months after stent placement does not significantly reduce the total number of cases of cardiovascular mortality, myocardial infarction, stroke, stent thrombosis or severe recurrence of ischaemia compared to treatment with clopidogrel. This is the conclusion of an international randomised study among patients who underwent stent placement. These findings are surprising, as CYP2C19 is needed to convert the pro-drug clopidogrel into the active metabolite that is responsible for the antithrombotic effect. Among patients with an allele that causes dysfunctional CYP2C19, however, ticagrelor was found to be superior to clopidogrel during the first 3 months after stent placement. The study did have a number of limitations and does not fully comply with current European guidelines. Thus, the evidence for the need for CYP2C19-guided thrombosis prophylaxis after stent placement remains inconclusive.

  • A randomised study did not find a statistically significant reduction of the risk of cardiovascular complications among patients with dysfunctional CYP2C19 treated with ticagrelor or prasugrel, in comparison with clopidogrel. 
  • The analysis did not distinguish between patients with a nearly completely inactive CYP2C19 enzyme (poor metabolizers) and those with reduced enzyme activity (intermediate metabolizers).
  • The limitations of the new study mean that it offers insufficient argument for adjusting the Dutch guidelines for the treatment of acute coronary syndrome.
  • After stent placement for stable coronary artery disease, clopidogrel can be safely prescribed without prior CYP2C19 genotyping.
  • Routine genotyping of all stent patients is too costly to be included in clinical practice on the basis of limited evidence.

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Authors

  • Sander van den Bogert, dr, pharmacist