Genes a part of PPI - Clopidogrel Interaction

1
Genes a Part of PPI-Clopidogrel Interaction

• P.Naina Mohamed
• Pharmacologist

2
Introduction

• TRIUMPH study, a prospective, multicenter
  registry looking at factors associated with
  racial differences in acute MI outcomes was
  carried out by Jeremiah Depta, MD, of Washington
  University in St. Louis and his colleagues to
  explore the issue according to both genotype and
  race.
• The current analysis included 2,062 patients who
  agreed to genetic testing and who were discharged
  on clopidogrel -- 79 were white and 21 were
  black. The participants were classified as having
  one of the following CYP2C19 genotypes
• 1 homozygotes -- wild-type, extensive
  metabolizers
• 2 carriers -- reduced function, poor
  metabolizers
• 17 carriers -- increased function,
  ultra-rapid metabolizers
• PPIs were used by 19 of whites and 15 of blacks
  either during the initial hospitalization or
  during the year after discharge. The most common
  PPIs taken were omeprazole (Prilosec),
  pantoprazole, and esomeprazole (Nexium).

3
Mechanism of Clopidogrel and PPIs interaction

• Clopidogrel (Prodrug)
• CYP2C19 metabolises Clopidogrel into its active
  metabolites
• PPIs (omeprazole, Pantoprazole and Esomeprazole)
  block CYP2C19 and inhibit the formation of active
  metaboiltes of Clopidogrel
• Reduced inhibition of Platelet aggregation
• Increased risk of Thrombosis
• Increased rate of cardiovascular events

4
Possible Mechanism of potential interaction
between Clopidogrel and PPIs in CYP2C1917
carriers

• CYP2C1917 (White Patients)
• 17 carriers have higher levels of the CYP2C19
  enzyme on which the PPIs can act
• Reduction of concentration of active metabolites
  of Clopidogrel
• Reduced platelet aggregation
• Increased rate of cardiac rehospitalisation

5
Conclusion

• TRIUMPH study was published as an abstract and
  presented at a conference. These data and
  conclusions should be considered to be
  preliminary until published in a peer-reviewed
  journal.
• If the patient is genotyped and he/she is a 17
  carrier, then potentially PPI use would not be
  recommended.
• But , the findings need to be validated in other
  studies.
• Without having that validation it's probably too
  premature to potentially say that we shouldn't
  use PPIs.

6
References

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