Comparative Effectiveness of Oral Anticoagulants in Atrial Fibrillation

 描述（由申请人提供）：房颤（AF）是一种常见的心律失常，影响超过200万美国人，并与发病率、死亡率和医疗保健费用增加相关。AF患者充分的抗血栓治疗对于预防卒中和其他并发症至关重要。迄今为止，这主要是通过维生素K拮抗剂（美国的华法林）实现的。然而，战争的使用是负担沉重的，并带来并发症的重大风险。最近，新的口服抗凝剂（OAC;达比加群、利伐沙班、阿哌沙班）在随机试验中被证明在预防AF患者卒中方面至少与华法林一样有效。然而，随机试验并不总是可以推广到通常的临床环境。因此，有必要进行额外的研究，以确定这些新的OAC与华法林相比的有效性，并确定更有可能从新药中获益的患者。在本申请中，我们建议评估以下具体目的：（1）评估新OAC与华法林治疗在预防缺血性卒中、全身性栓塞、医疗利用和死亡率方面的有效性;（2）评估出血和其他并发症的风险（心肌梗死，消化不良）与这些患者中使用新OAC相比华法林相关;（3）确定患者亚组，按年龄，性别，种族/民族定义， 合并症和其他药物的使用，新OAC对这些合并症和其他药物特别有益或有害;以及（4）开发和验证使用新OAC的AF患者中卒中/心源性栓塞并发症和严重出血的风险预测模型。为了解决这些研究问题，我们将使用两个大型索赔数据库，OptumInsight和MarketScan。这些数据库包括超过100万AF患者的健康保险索赔，以及> 155，000名新OAC用户。比较有效性研究的最新方法，包括高维倾向评分、边际结构模型和工具变量，将用于调整混杂因素。我们的研究结果将提供关键证据，帮助患者和临床医生做出关于抗凝治疗的决定，平衡与不同治疗方案相关的获益和风险。该提案也有可能为监管机构、保险公司、卫生系统领导人和专业组织在上市后批准、报销和临床指南等问题上的决策提供信息。

 DESCRIPTION (provided by applicant): Atrial fibrillation (AF), a common cardiac arrhythmia, affects >2 million Americans and is associated with increased morbidity, mortality, and healthcare costs. Adequate antithrombotic treatment in AF is critical to preventing stroke and other complications. To date, this has been mostly achieved with vitamin K antagonists (warfarin in the US). Warfarin use, however, is burdensome and carries a significant risk of complications. Recently, new oral anticoagulants (OACs; dabigatran, rivaroxaban, apixaban) have proved in randomized trials to be at least as efficacious as warfarin in preventing stroke in AF patients. Randomized trials, however, are not always generalizable to the usual clinical setting. Therefore, additional research is necessary to determine the effectiveness of these new OACs, compared to warfarin, and to identify patients more likely to benefit from the new medications. In this application, we propose to assess the following specific aims: (1) to estimate the effectiveness of new OACs versus warfarin treatment in the prevention of ischemic stroke, systemic embolism, healthcare utilization, and mortality;(2) to assess the risk of bleeding and other complications (myocardial infarction, dyspepsia) associated with use of new OACs versus warfarin in these patients; (3) to identify patient subgroups, defined by age, sex, race/ethnicity, comorbidities, and use of other medications, for which the new OACs are particularly beneficial or hazardous; and (4) to develop and validate risk predictive models of stroke / cardioembolic complications and severe hemorrhage in AF patients using new OACs. To address these research questions, we will use two large claim databases, OptumInsight and MarketScan. These databases include health insurance claims from over 1 million patients with AF, and >155,000 users of new OACs. State- of-the-art methods for comparative effectiveness research, including high-dimensional propensity scores, marginal structural models, and instrumental variables, will be used to adjust for confounding. Results from our research will provide key evidence to help patients and clinicians make decisions about their anticoagulant treatment, balancing benefits and risks associated with different therapeutic options. This proposal also has the potential to inform decisions by regulatory agencies, insurers, health system leaders, and professional organizations in issues such as post marketing approval, reimbursements, and clinical guidelines.