| 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-1：Management of low dose aspirin and clopidogrel in clinical practice - A GI perspective |
| 演者 | Lanas Angel（University of Zaragoza, Spain） |
| 共同演者 | |
| 抄録 | Low dose aspirin（ASA）therapy has been associated with a wide spectrum of lesions and adverse events in the upper GI tract, which may lead to poor adherence or discontinuation of the antiplatelet therapy and increases the risk of recurrent acute coronary event. A recent meta-analysis of RCTs estimated that the risk of major GI bleeding increases in ASA users（OR=1.55；95% CI：1.27-1.90）. The controversy still exists on whether ASA induces GI bleeding from pre-existing lesions or from“de novo”induced mucosal lesions. Probably both causes co-exist since low-dose ASA may decrease gastric mucosal prostaglandins and induce mucosal lesions. Death is the worst outcome of GI complications, but ASA related mortality due to GI bleeding is scarce. The Spanish Mortality Study estimated rates of 18 deaths/100,000 low-dose aspirin users. Aspirin might affect the lower GI tract and induce protein loss, small bowel bleeding and iron deficiency anemia. In healthy volunteers low dose enteric-coated ASA is associated with some damage in 50% of volunteers. ASA has been also associated with the development of colonic diverticulitis and diverticular bleeding. To prevent the risk of GI complications the lowest dose of aspirin should be used（?100 mg/day）. In patients with history of peptic ulcer or receiving concomitant NSAIDs or other antithrombotic agent, co-therapy with gastroprotective drug is advised and PPIs are currently the most widely used strategy. Eradication of H. pylori is recommended in case of ulcer history. Concomitant use of ASA with either Naproxen or Ibuprofen should be avoided, due to interaction with the antiplatelet effect. Clopidogrel alone, or combined with ASA is often recommended. Clopidogrel is metabolized to the active metabolite via the cytochrome P450 system, principally CYP2C19. PPI could competitively inhibit the enzyme and impair metabolism of clopidogrel. Observational studies have suggested that use of a PPI in combination with clopidogrel may increase the risk of CV events. Post hoc analyses of different studies and the COGENT trial have failed to demonstrate this interaction is clinically significant. |
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