| セッション情報 | The 4th International ForumI Drug-associated GI Injury：Advances of the pathogenesis and recent clinical topics 2. Recent clinical topics（a）Antiplatelet therapy：Mucosal injuries and drug interaction with PPI |
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| タイトル | IFI-2a-3：Proton pump inhibitors and antiplatelet agents：Safe to prescribe together? |
| 演者 | Abraham Neena S.（Department of Medicine, Division of Gastroenterology, Mayo Clinic College of Medicine, USA） |
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| 抄録 | Dual antiplatelet therapy（aspirin+thienopyridine）is recommended for the treatment of acute coronary syndrome and to prevent stent thrombosis following coronary intervention with stent insertion, but is associated with a 78-96% increased risk of GI bleeding when compared to aspirin alone. This risk is reduced 66% with concomitant PPI prescription. Early studies demonstrated co-administration of omeprazole reduced antiplatelet activity of the thienopyridine clopidogrel due to a suspected drug-drug interaction. However, differences in cardiac comorbidity and prescription channeling was observed in these studies, whereby PPI agents were prescribed in sicker patients―thus, introducing significant confounders. The COGENT trial and post-hoc analyses of the PLATO trial showed no significant association of PPI with CV events. Genes have since been identified that modulate thienopyridine metabolic activity（CYP3A5 and CYP2C19）, absorption（ABCB1）, and biologic activity（P2RY12 and ITGB3）. Activation by CYP2C19 is a crucial determinant of clopidogrel pharmacodynamic and clinical efficacy. Variant alleles involved in clopidogrel metabolism（CYP2C19）and absorption（ABCB1）are linked to increased rate of death, stroke or MI. CYP2C19 metabolic status（rapid, extensive, intermediate, or poor）is also a major determinant of early stent thrombosis. Prasugrel and ticagrelor, 3rd-generation thienopyridines, are alternatives for patients with genetic polymorphisms as they are unaffected by CYP2C19 variant alleles；prasugrel is also unaffected by ABCB1 variants. However, 3rd-generation thienopyridines are associated with higher rates of bleeding, with the most common bleeding site being gastrointestinal. |
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