Drug Interactions Affecting Oral Anticoagulant Use.
Drug Interactions Affecting Oral Anticoagulant Use.
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DOI：
10.1161/circep.121.007956
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发表时间：
2022-06
影响因子：
8.4
通讯作者：
Olshansky, Brian
中科院分区：
文献类型：
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作者：
Mar, Philip L.;Gopinathannair, Rakesh;Gengler, Brooke E.;Chung, Mina K.;Perez, Arturo;Dukes, Jonathan;Ezekowitz, Michael D.;Lakkireddy, Dhanunjaya;Lip, Gregory Y. H.;Miletello, Mike;Noseworthy, Peter A.;Reiffel, James;Tisdale, James E.;Olshansky, Brian
口服抗凝剂（OAC）是房颤和其他心血管疾病患者常用的药物。华法林和直接口服抗凝剂（DOAC）都容易发生药物-药物相互作用（DDI）。DDI是药物不良反应的重要原因，对医疗保健系统造成了很大的影响。华法林的DDI主要涉及细胞色素P450 (CYP) 2C9的中强抑制剂/诱导剂，该抑制剂负责消除华法林更有效的s -异构体。然而，CYP3A4和CYP1A2的抑制剂/诱导剂也可能引起华法林的DDI。认识到这些沉淀剂，并在使用或停用这些药物时增加监测频率，将最大限度地减少华法林DDI的影响。DOAC DDI主要受强烈影响通透性糖蛋白（P-gp）的药物的影响，较小程度上受强CYP3A4抑制剂/诱导剂的影响。达比加群和依多沙班受P-gp调制的影响。所有服用DOAC的患者应避免使用强效CYP3A4或P-gp诱导剂，除非先前证明是安全的。服用阿哌沙班和利伐沙班的患者应避免同时使用强CYP3A4和P-gp抑制剂。同时使用抗血小板/抗凝剂会增加出血的风险，但在许多情况下，它们的联合使用是不可避免的。根据循证临床指南，缩短抗凝/抗血小板联合治疗的持续时间是降低出血风险的最佳途径。
Oral anticoagulants (OAC) are medications commonly used in patients with atrial fibrillation and other cardiovascular conditions. Both warfarin and direct oral anticoagulants (DOAC) are susceptible to drug-drug interactions (DDI). DDI are an important cause of adverse drug reactions and exact a large toll on the healthcare system. DDI for warfarin mainly involve moderate to strong inhibitors / inducers of cytochrome P450 (CYP) 2C9, which is responsible for the elimination of the more potent S-isomer of warfarin. However, inhibitor / inducers of CYP3A4 and CYP1A2 may also cause DDI with warfarin. Recognition of these precipitating agents along with increased frequency of monitoring when these agents are initiated or discontinued will minimize the impact of warfarin DDI. DOAC DDI are mainly affected by medications strongly affecting the permeability glycoprotein (P-gp), and to a lesser extent, strong CYP3A4 inhibitors / inducers. Dabigatran and edoxaban are affected by P-gp modulation. Strong inducers of CYP3A4 or P-gp should be avoided in all patients taking DOAC unless previously proven to be otherwise safe. Simultaneous strong CYP3A4 and P-gp inhibitors should be avoided in patients taking apixaban and rivaroxaban. Concomitant antiplatelet / anticoagulant use confers additive risk for bleeding, but their combination is unavoidable in many cases. Minimizing duration of concomitant anticoagulant/antiplatelet therapy as indicated by evidence-based clinical guidelines is the best way to reduce the risk of bleeding.