4.1 Article

Effects of individualized antiplatelet therapy, based on CYP2C19 genotyping, on platelet function in patients underwent percutaneous coronary intervention

Journal

PERFUSION-UK
Volume 37, Issue 1, Pages 78-85

Publisher

SAGE PUBLICATIONS LTD
DOI: 10.1177/0267659120978584

Keywords

acute coronary syndrome; antiplatelet therapy; clopidogrel; gene polymorphism; platelet reactivity

Funding

  1. Medical and Health Science and Technology Development Projects of Shandong [2015WS0218]
  2. Science and Technology Innovation Program for Clinical Medicine of Jinan [201602176]
  3. National Natural Science Foundation of China [81770334, 81970281]
  4. Taishan Scholar Engineering Construction Fund of Shandong Province [ts201511104]
  5. Academic promotion programme of Shandong First Medical University [2019QL012]

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Individualized antiplatelet therapy based on CYP2C19 genotyping can reduce the incidence of high on-treatment platelet reactivity in ACS patients after PCI, providing guidance for antiplatelet therapy management.
Objective: To evaluate the effect of individualized antiplatelet therapy, based on CYP2C19 genotyping, on platelet function in patients underwent PCI and to compare this treatment with conventional antiplatelet therapy. Methods: All patients were treated with 100 mg aspirin once a day. Additionally, the CA group received 75 mg clopidogrel once a day. The IA group was divided into extensive metabolizers (EMs, no loss-of-function, i.e. LOF allele, 75 mg clopidogrel once a day), intermediate metabolizers (IMs, carrying one LOF alleles, 75 mg clopidogrel twice daily), and poor metabolizers group (PMs, carrying two LOF alleles, 90 mg ticagrelor twice daily). After taking these antiplatelet medications for > 5 days, we assessed platelet function by thromboelastography, and recorded the MA(ADP) (maximum amplitude produced by adenosine diphosphate) value. MA(ADP) > 47 mm was defined as residual HPR, indicating a high risk of thrombosis. MA(ADP) <= 31 mm indicated a high risk of bleeding. Results: The proportion of patients with MA(ADP) > 47 mm was significantly lower in the IA group (29.6%) than the CA group (38.1%). The proportion of patients with MA(ADP) <= 31 mm was significantly higher in the IA group (31.0%) than the CA group (21.3%). No significant differences were found in the proportions of patients with MA(ADP) > 47 mm or MA(ADP) <= 31 mm when compared between the EMs and IMs group. Conclusion: Individualized antiplatelet therapy, based on CYP2C19 genotyping, can reduce the incidence of HPR in ACS patients after PCI compared to conventional therapy. By taking a double dose of clopidogrel, patients with a CYP2C19 LOF allele can therefore overcome the reduced efficacy of clopidogrel associated with LOF alleles without increasing the risk of bleeding, which is of guiding significance for the management of antiplatelet therapy on ACS patients after PCI especially considering the CYP2C19 LOF alleles that carry an important predictor for the ischemic events.

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