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)，并具体回应NHLBI RC2关于成人房颤患者的比较有效性的主题。房颤是成人最常见的临床显著心律失常，也是导致缺血性中风和其他系统性血栓栓塞症的最重要的危险因素之一。目前影响着250万至500万美国人，随着全国人口老龄化，其患病率将显着增加。在选定人群中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)和药物心律失常控制，以及许多早期研究评估了新出现的非药物干预措施(如导管消融和外科消融)。然而，关于这一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严重的心房颤动患者群体，仍存在争议。此外，现有的随机试验还不能检验不同的联合治疗方法的多样性，也不能对当代治疗时代的代表性人群和相关患者亚组的潜在风险和好处提供现实的估计。此外，我们缺乏可靠的风险分层方案，这些方案已经在大量不同的人群中得到验证，并解决了单个患者中风风险和治疗相关结果的显著差异。最后，我们对房颤的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，我们将利用我们来自房颤中的抗凝和风险因素(Atria)研究、国家心肺和血液研究所赞助的心血管研究网络(CVRN)(一个基于医疗计划的多中心研究联盟)以及来自心房颤动的前哨随机临床试验的数据的专业知识，以创建一支无与伦比的多学科团队和资源。拟议的项目将在基于人群的研究人员、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，通过仔细描述当代约40,000名成人心房颤动患者的队列，以改进比较有效性研究、结果的风险分层以及未来心房颤动的观察性研究和随机试验的规划和进行。我们建议完成以下三个具体目标：目标1：开发和测试来自大规模社区队列的房颤患者血栓栓塞症(缺血性中风和全身性血栓栓塞症)的新的风险分层方案，并根据房颤随机临床试验的丰富数据集验证所产生的风险模型。目的2：建立和描述在非常大的、不同的社区人群中发生的心房颤动的当代登记，以提供对当前结局事件发生率和实践模式、潜在的健康差异的重要见解，并促进更快地登记参加未来的有效性研究和临床试验以及改进的风险分层模型的开发。目的3：确定和验证最优设计和分析方法，以减少房颤患者观察性研究中比较有效性分析(例如，不同的抗血栓策略)的混淆和偏差。 公共卫生相关性：房颤是成人最常见的临床显著心律失常，也是导致缺血性中风和其他系统性血栓栓塞症的最重要的危险因素之一。它目前影响着数以百万计的美国人，预计在未来几十年内其流行率将大幅上升。虽然已经开发了多种策略来降低心房颤动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价值有限。此外，关于不同疗法在临床实践中的比较有效性的数据很少。这项拟议的研究将提供一套关键的研究资源，以改进风险预测，促进更有效的比较有效性分析，并简化未来心房颤动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.