CYP2C19 and CYP3A4 Activity and ADP-induced Platelet Reactivity in Patients with STEMI Treated by Prasugrel or Ticagrelor



Year of publication 2018
Type Appeared in Conference without Proceedings
Description Aim: We assessed the contribution of CYP2C19 and CYP3A4 metabolic activity to the ADP-induced platelet aggregation 1h and 24h after the loading dose of 60 mg prasugrel or 180 mg ticagrelor in the patients with ST-elevations myocardial infarction (STEMI) treated by percutaneous coronary intervention. Further, we assessed the contribution of CYP2C19 polymorphisms and amiodarone treatment to the CYP 450 enzymatic activity. Methods: Total number of 89 patients with STEMI were randomly assigned to the treatment with prasugrel (n = 46) or ticagrelor (n = 43). Metabolic activity of CYP2C19 and CYP3A4 was assessed by the rate of 5-hydroxylation and sulfoxidation of lansoprazole. Further, patients were genotypized for CYP2C19 *2 and *17 alleles and the data about concomitant treatment were collected, where amiodarone was considered as CYP3A4 inhibitor. Results: In prasugrel-treated patients, high ADP-induced platelet reactivity 1h after the loading dose negatively correlated with lansoprazole-sulfone/lansoprazole ratio, which reflects CYP3A4 metabolic activity (r = -0.35, p = 0.018) and positively with 5OH-lansoprazole/lansoprazole ratio (r = 0.44, p = 0.002). There was no significant effect with respect to CYP2C19 or CYP3A4 metabolic activity after 24h or in the ticagrelor group. CYP2C19 poor metabolizers had lower 5OH-lansoprazole/lansoprazole ratio and higher lansoprazole-sulfone/lansoprazole ratio compared to the intermediate and extensive metabolizers, but this was not reflected in the ADP-induced platelet reactivity. The treatment with amiodarone did not influence neither the metabolic ratios nor the ADP-induced platelet reactivity. Conclusions: The CYP3A4 and CYP2C19 metabolic activity is associated with ADP-induced platelet reactivity in prasugrel-treated, but not ticagrelor-treated patients with STEMI.

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