Should we test for CYP2C9 before initiating anticoagulant therapy in patients with atrial fibrillation?
Should we test for CYP2C9 before initiating anticoagulant therapy in patients with atrial fibrillation?
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在房颤患者开始抗凝治疗之前，我们是否应该检测 CYP2C9？
DOI：
10.1007/s11606-009-0927-7
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发表时间：
2009
影响因子：
5.7
通讯作者：
Rosand,Jonathan
中科院分区：
文献类型：
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作者：
Eckman,MarkH;Greenberg,StevenM;Rosand,Jonathan
背景华法林敏感基因CYP2C9的遗传变异与华法林启动期间出血风险的增加有关。研究还表明，这些患者在整个治疗过程中仍然处于危险之中。目的在开始使用华法林之前，对非瓣膜性心房颤动(AF)患者进行CYP2C9检测是否能改善预后？设计马尔可夫状态转换决策模型。设置动态或住院环境，需要新的抗凝治疗。患者的基本病例是一名69岁的男性新近诊断为非瓣膜性房颤。干预措施包括：(1)华法林，(2)阿司匹林，或(3)在没有进行基因测试的情况下不进行抗血栓治疗；以及(4)对携带CYP2C9等位基因的患者进行基因测试，然后(4)使用阿司匹林或(5)不进行抗血栓治疗。测量质量调整寿命年(QALY)。结果在基础病例中，检测和治疗CYP2C9*2和/或CYP2C9*3的患者使用阿司匹林比使用华法林更好(8.97 QALY)。然而，没有进行基因检测的华法林紧随其后(8.96 QALY)，大约相差5天。敏感性分析表明，对于血栓事件风险较低的患者，基因测试后再服用阿司匹林是最好的。如果每年血栓事件的发生率大于5%，或者在接受华法林治疗时大出血的风险较低，则首选未经检测的华法林。结论对于因房颤而发生缺血性卒中的平均风险和平均大出血风险的患者，基于基因检测的治疗与未经检测的华法林治疗相比没有好处。在血栓事件风险较低或出血风险较高的患者中，测试的收益可能会更大。
BackgroundGenetic variants of the warfarin sensitivity geneCYP2C9have been associated with increased bleeding risk during warfarin initiation. Studies also suggest that such patients remain at risk throughout treatment.ObjectiveWould testing patients with non-valvular atrial fibrillation (AF) forCYP2C9before initiating warfarin improve outcomes?DesignMarkov state transition decision model.SettingAmbulatory or inpatient settings necessitating new initiation of anticoagulation.PatientsThe base case was a 69-year-old man with newly diagnosed non-valvular AF. Interventions included: (1) warfarin, (2) aspirin, or (3) no antithrombotic therapy without genetic testing; and genetic testing followed by (4) aspirin or (5) no antithrombotic therapy in those with culpritCYP2C9alleles.MeasuresQuality-adjusted life years (QALYs).ResultsIn the base case, testing and treating patients withCYP2C9*2and/orCYP2C9*3with aspirin rather than warfarin was best (8.97 QALYs). However, warfarin without genetic testing was a close second (8.96 QALYs), a difference of roughly 5 days. Sensitivity analyses demonstrated that genetic testing followed by aspirin was best for patients at lower risk of embolic events. Warfarin without testing was preferred if the rate of embolic events was greater than 5% per year, or the risk of major bleeding while receiving warfarin was lower.ConclusionFor patients at average risk for ischemic stroke due to AF and at average risk for major hemorrhage, treatment based on genetic testing offers no benefit compared to warfarin initiation without testing. The gain from testing may be larger in patients at lower risk of embolic events or at greater risk of bleeding.