Division of Cardiology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
Curr Opin Cardiol. 2012 Nov;27(6):642-50. doi: 10.1097/HCO.0b013e32835830b6.
To review the current evidence on the clinical significance of the drug-drug interactions between the available antiplatelet agents and proton pump inhibitors (PPIs).
Gastrointestinal bleeding is associated with higher rates of morbidity and mortality following a myocardial infarction. PPIs are commonly used to prevent gastrointestinal bleeding. PPIs can attenuate metabolism of clopidogrel to its active metabolite by inhibiting various hepatic CYP450 enzymes, mainly CYP2C19. Concomitant use of a PPI with clopidogrel reduces clopidogrel active metabolite generation and subsequent platelet inhibition. In observational studies, the clinical significance of this drug-drug interaction is mixed. Evidence from the only randomized trial studying the clinical implications of the PPI-clopidogrel interaction did not demonstrate any difference in cardiovascular outcomes but did show a reduction in gastrointestinal bleeding with use of a PPI.
The drug-drug interaction between antiplatelet agents and PPIs at the enzymatic level does not seem to result in worse clinical outcomes. The risk of gastrointestinal bleeding with antiplatelet therapy is substantial. Clinicians should use PPIs in selected high-risk patients to prevent gastrointestinal bleeding.
回顾现有抗血小板药物与质子泵抑制剂（PPIs）之间药物相互作用的临床意义的证据。
心肌梗死后，胃肠道出血与更高的发病率和死亡率相关。PPIs 常用于预防胃肠道出血。PPIs 通过抑制各种肝 CYP450 酶（主要是 CYP2C19）来抑制氯吡格雷转化为其活性代谢物。同时使用 PPI 和氯吡格雷会减少氯吡格雷活性代谢物的生成和随后的血小板抑制。在观察性研究中，这种药物相互作用的临床意义是混杂的。唯一一项研究 PPI-氯吡格雷相互作用对临床影响的随机试验的证据表明，心血管结局没有差异，但使用 PPI 确实减少了胃肠道出血。
抗血小板药物和 PPIs 在酶水平上的药物相互作用似乎不会导致更差的临床结局。抗血小板治疗引起胃肠道出血的风险很大。临床医生应在选择的高危患者中使用 PPI 预防胃肠道出血。
