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“大机遇”（RC 2），并特别回应了NHLBI RC 2主题“房颤成人患者中的比较有效性”。心房颤动是成人中最常见的具有临床意义的心律失常，也是缺血性中风和其他全身性血栓栓塞的最潜在危险因素之一。目前，它影响了250 - 500万美国人，随着全国人口老龄化，其患病率将显著增加。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（例如，维生素K拮抗剂、抗血小板剂、其他）和药物性心律失常控制，并且许多早期研究已经评估了新兴的非药物性干预（例如，导管消融术和手术消融术）。然而，关于该结果如何适用于在典型临床实践中接受治疗的更多样化和病情更重的房颤患者人群仍然存在争议。此外，现有的随机试验还不能检查各种不同的联合治疗方法，或提供现实的估计潜在的风险和利益的代表性人群在当代治疗时代和相关的患者亚组。此外，我们缺乏强有力的风险分层方案，这些方案已在大量不同人群中得到验证，并解决了个体患者中卒中风险和治疗相关结局的显著差异。最后，关于房颤临床人群中是否存在健康差异的数据有限，包括治疗策略和选定患者特征对房颤相关结局的影响。为了解决NIH RFA-OD-09-004中强调的这些主要知识差距，我们将利用我们来自房颤（ATRIA）抗凝和风险因素研究的专业知识，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，以及来自房颤哨兵随机临床试验的数据，以创建无与伦比的多学科团队和资源。拟议的项目将建立基于人群的研究人员，试验者和方法学家之间的独特合作，以及通过一个精心表征的当代约40，000名心房颤动成年人队列建立一个独特的研究平台，以改善比较有效性研究，结局的风险分层，以及未来心房颤动观察性研究和随机试验的规划和实施。我们建议实现以下三个具体目标：目标1：在来自大规模社区队列的房颤患者中开发和测试血栓栓塞（缺血性卒中和全身性血栓栓塞）的新风险分层方案，并根据来自房颤随机临床试验的丰富数据集验证所得风险模型。目标二：在非常大的、多样化的社区人群中建立和描述房颤事件的当代登记，以提供对当前结局事件发生率和实践模式、潜在健康差异的重要见解，并促进更快地入组未来的有效性研究和临床试验，以及开发改进的风险分层模型。目标3：确定并验证最佳设计和分析方法，以减少比较有效性分析的混淆和偏差（例如，不同的抗血栓策略）。 公共卫生相关性：心房颤动是成人最常见的有临床意义的心律失常，也是缺血性卒中和其他全身性血栓栓塞的最有力的危险因素之一。它目前影响着数百万美国人，预计在未来几十年内其患病率将大幅增加。虽然已经开发了多种策略来降低房颤相关不良事件的风险，但现有的风险分层方案在指导治疗决策方面的临床实用性有限。此外，在临床实践中，关于不同疗法的比较有效性的数据很少。拟议的研究将提供一组关键的研究资源，以改善风险预测，促进更有效的比较有效性分析，并简化未来房颤随机临床试验的规划和实施。

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.