Contemporary Treatment and Outcomes for Atrial Fibrillation in Clinical Practice

描述（由申请人提供）：本申请涉及NIH RFA-OD-09-004: NHLBI参与研究和研究基础设施“重大机遇”（RC2），并特别回应NHLBI RC2关于成人房颤比较有效性的主题。房颤是成人最常见的临床显著性心律失常，也是缺血性卒中和其他系统性血栓栓塞的最有效危险因素之一。目前有250 - 500万美国人患有此病，随着全国人口的老龄化，其发病率将显著上升。在选定人群中进行的许多随机对照试验比较了卒中预防策略（如维生素K拮抗剂、抗血小板药物等）和药理学心律失常控制，许多早期研究评估了新兴的非药理学干预措施（如导管消融和手术消融）。然而，关于结果如何适用于典型临床实践中治疗的更多样化和病情更严重的房颤患者群体，争议仍然存在。此外，现有的随机试验无法检验各种不同的联合治疗方法，也无法在当代治疗时代和相关患者亚组的代表性人群中提供潜在风险和益处的现实估计。此外，我们缺乏强有力的风险分层方案，这些方案已在大型、多样化的人群中得到验证，并解决了个体患者中风风险和治疗相关结果的显著差异。最后，关于房颤临床人群中是否存在健康差异的数据有限，无论是在治疗策略方面，还是在选定的患者特征对房颤相关结果的影响方面。为了解决NIH RFA-OD-09-004中强调的这些主要知识差距，我们将利用我们在房颤（ATRIA）研究中的抗凝血和危险因素，国家心肺血液研究所赞助的心血管研究网络（CVRN），一个多中心，基于健康计划的研究联盟的专业知识，以及房颤的哨点随机临床试验的数据，创建一个无与伦比的多学科团队和资源。拟议的项目将在以人群为基础的研究人员、试验人员和方法学家之间建立一个独特的合作，以及一个独特的研究平台，通过一个精心描述的约40,000名房颤成年患者的当代队列来改进比较有效性研究、结果的风险分层、以及未来房颤观察性研究和随机试验的计划和实施。我们建议实现以下三个具体目标：目标1：从大规模社区队列中开发和测试房颤患者血栓栓塞（缺血性卒中和全身性血栓栓塞）的新型风险分层方案，并根据房颤随机临床试验的丰富数据集验证由此产生的风险模型。目标2：在非常大的、多样化的社区人群中建立和描述发生心房颤动的当代登记，以提供对当前结果事件率和实践模式、潜在健康差异的关键见解，并促进更快速地纳入未来的有效性研究和临床试验，以及改进风险分层模型的发展。目的3：在房颤患者的观察性研究中，确定并验证优化设计和分析方法，以减少比较有效性分析（例如，不同的抗血栓策略）的混淆和偏倚。

DESCRIPTION (provided by applicant): This application addresses NIH RFA-OD-09-004: NHLBI Participation in Research and Research Infrastructure "Grand Opportunities" (RC2) and specifically responds to the NHLBI RC2 topic of Comparative Effectiveness among adults with atrial fibrillation. Atrial fibrillation is the most common clinically significant arrhythmia in adults and one of the most potent risk factors for ischemic stroke and other systemic thromboembolism. It affects 2.5-5 million Americans currently and its prevalence will increase markedly with the aging of the population nationally. Numerous randomized controlled trials in selected populations have compared stroke prevention strategies (e.g., vitamin K antagonists, antiplatelet agents, other) and pharmacologic arrhythmia control, and numerous earlier phase studies have assessed emerging non-pharmacologic interventions (e.g., catheter ablation and surgical ablation). However, controversy remains about how the results apply to the more diverse and sicker population of atrial fibrillation patients treated in typical clinical practice. Furthermore, existing randomized trials have not been able to examine the variety of different combined treatment approaches or provide realistic estimates of potential risks and benefits in representative populations in the contemporary treatment era and relevant patient subgroups. In addition, we lack robust risk stratification schemes that have been validated among large, diverse populations and that address the significant variability in the risks of stroke and treatment-related outcomes among individual patients. Finally, we have limited data about whether health disparities exist within clinical populations of atrial fibrillation, both with regard to treatment strategies and the influence of selected patient characteristics on atrial fibrillation-related outcomes. To address these major knowledge gaps highlighted in NIH RFA-OD-09-004, we will leverage our expertise from the Anticoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study, the National Heart, Lung and Blood Institute-sponsored Cardiovascular Research Network (CVRN), a multicenter, health plan-based research consortium, as well as data from sentinel randomized clinical trials in atrial fibrillation to create an unparalleled multidisciplinary team and resources. The proposed project will establish a unique collaboration among population-based researchers, trialists, and methodologists as well as a unique research platform through a carefully characterized contemporary cohort of ~40,000 adults with atrial fibrillation to improve comparative effectiveness studies, risk stratification of outcomes, and the planning and conduct of future observational studies and randomized trials for atrial fibrillation. We propose to accomplish the following three Specific Aims: Aim 1: Develop and test novel risk stratification schemes for thromboembolism (ischemic stroke and systemic thromboembolism) in patients with atrial fibrillation from a large-scale community-based cohort and additionally validate the resulting risk models against rich datasets from randomized clinical trials in atrial fibrillation. Aim 2: Establish and characterize a contemporary registry of incident atrial fibrillation within very large, diverse community-based populations to provide critical insights into current outcome event rates and practice patterns, potential health disparities, and to facilitate more rapid enrollment into future effectiveness studies and clinical trials as well as development of improved risk stratification models. Aim 3: Identify and validate optimal design and analytic approaches to reduce confounding and bias for comparative effectiveness analyses (e.g., different antithrombotic strategies) in observational studies of patients with atrial fibrillation. PUBLIC HEALTH RELEVANCE: Atrial fibrillation is the most common clinically significant arrhythmia in adults and one of the most potent risk factors for ischemic stroke and other systemic throm-boembolism. It currently affects millions of Americans and its prevalence is expected to increase substantially during the next several decades. While multiple strategies have been developed to reduce the risks of atrial fibrillation-related adverse events, existing risk stratification schemes are of limited clinical utility in guiding treatment decisions. Furthermore, few data exist about the comparative effectiveness of different therapies in clinical practice. The proposed study will provide a critical set of research resources to improve risk prediction, facilitate more valid comparative effectiveness analyses, and streamline the planning and conduct of future randomized clinical trials in atrial fibrillation.