Eckman Mark H, Wong Lawrence K S, Soo Yannie O Y, Lam Wynnie, Yang Song Ran, Greenberg Steven M, Rosand Jonathan
Division of General Internal Medicine and the Center for Clinical Effectiveness, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0535, USA.
Stroke. 2008 Dec;39(12):3308-15. doi: 10.1161/STROKEAHA.108.523159. Epub 2008 Oct 9.
Intracerebral hemorrhage (ICH) accounts for a majority of long-term morbidity and mortality associated with bleeding while on warfarin. Both ICH and warfarin-related ICH appear to have a genetic component. Furthermore, advanced neuroimaging using MRI can now identify individuals at increased risk of ICH. We explore whether screening strategies that include genetic profiling and neuroimaging might improve the safety of chronic anticoagulation for atrial fibrillation by identifying individuals from whom warfarin should be withheld.
We used a Markov state transition decision model. Effectiveness was measured in quality-adjusted life-years. Data sources included the English language literature using MEDLINE searches and bibliographies from selected articles along with empirical data from our institutions. The base case was a 69-year-old man with newly diagnosed nonvalvular atrial fibrillation.
For patients at average risk for thromboembolic events and known to possess a hypothetical genetic profile increasing risk for warfarin ICH, anticoagulation remains the preferred strategy until the relative hazard of ICH exceeds 23.8. Genetic profiling would be favored for patients at low risk of thromboembolism (1.5% per year) if the hypothetical gene variant(s) conferred a relative risk of ICH >4.1. Screening strategies in which patients underwent genotyping and MRI before anticoagulation did not improve aggregate patient outcomes unless the predictive power of MRI exceeded current best guess estimates and patients were at low to moderate risk of thromboembolism.
Currently identified genetic markers of bleeding risk do not confer a risk of ICH sufficiently high to warrant routine genetic testing for patients at average risk of thromboembolism. Even if patients undergo screening with MRI as well as genotyping, currently available data on the role of MRI on risk of ICH and warfarin ICH do not support use of these tests for withholding anticoagulation in patients with atrial fibrillation.
在服用华法林期间发生的脑出血（ICH）是导致出血相关长期发病和死亡的主要原因。ICH以及与华法林相关的ICH似乎都有遗传因素。此外，利用磁共振成像（MRI）的先进神经影像学检查现在能够识别出ICH风险增加的个体。我们探讨了包括基因分析和神经影像学检查在内的筛查策略是否可以通过识别应停用华法林的个体来提高房颤患者长期抗凝治疗的安全性。
我们使用了马尔可夫状态转换决策模型。疗效以质量调整生命年衡量。数据来源包括通过MEDLINE检索的英文文献、所选文章的参考文献以及我们机构的经验数据。基础病例是一名新诊断为非瓣膜性房颤的69岁男性。
对于血栓栓塞事件平均风险且已知具有假设的增加华法林所致ICH风险的基因特征的患者，在ICH的相对风险超过23.8之前，抗凝治疗仍然是首选策略。如果假设的基因变异使ICH的相对风险>4.1，对于血栓栓塞低风险（每年1.5%）的患者，基因分析将更受青睐。除非MRI的预测能力超过目前的最佳猜测估计且患者血栓栓塞风险为低至中度，否则在抗凝治疗前对患者进行基因分型和MRI检查的筛查策略并不能改善总体患者结局。
目前确定的出血风险基因标记所带来的ICH风险不够高，不足以对血栓栓塞平均风险的患者进行常规基因检测。即使患者同时接受MRI筛查和基因分型，目前关于MRI在ICH和华法林所致ICH风险方面作用的数据也不支持将这些检查用于房颤患者停用抗凝治疗。
