Optimizing Atrial Fibrillation Management in CKD

摘要 心房颤动（AF）是最常见的持续性心律失常，目前影响全球超过3350万成年人， 范围广，在北美的比率最高。慢性肾脏疾病（CKD）也非常普遍， 影响了14%的美国和北美人口。CKD患者的AF负担高3倍， 高达25%的CKD患者。AF与不良结局有关。我们的数据表明， CKD、偶发性AF与心力衰竭（HF）、急性冠状动脉综合征（ACS） (ACS)、卒中、死亡和进展为终末期肾病（ESRD）与无AF的CKD患者相比。 由于房颤相关的高风险，尚不清楚房颤治疗是否能改善CKD患者的结局。 CKD中AF的独特病理生理学、肾清除率降低的影响以及竞争性 非AF相关死亡的风险可能会改变常用AF药物的有效性和安全性， CKD中的程序。据我们所知，没有发表的研究评估了AF的集体影响 CKD患者的肾脏和心血管结局。房颤治疗试验在很大程度上排除了 CKD患者。先前的观察性研究有几个明显的局限性：（1）仅关注华法林， 未对其他AF治疗进行综合评价;（2）仅关注卒中和死亡结局;以及（3） 对可能影响房颤治疗的接受和结局的临时临床措施考虑不足。 我们的总体目标是使用“真实世界”的当代数据来评估各种AF的风险与受益 治疗，包括药物和程序，在成人CKD。我们将进行比较 描述AF治疗是否影响重要肾脏和心血管的有效性分析 CKD患者与非CKD患者的结局。为了实现这些目标，我们将利用心血管研究 网络（CVRN）平台，以研究来自两个国家的约267，000名AF患者的社区网络 参与加州的医疗保健系统;我们将在社区外部验证这些发现- 基于加拿大安大略约392，000例患者的队列。我们将评估使用，反应和安全性 目前的AF治疗（包括抗凝、心率控制剂、抗心律失常药物和AF相关药物） 在CKD患者与非CKD患者中进行比较。我们将进行比较有效性分析， AF治疗是否会影响有或无AF患者的重要肾脏和心血管结局 CKD。本研究的数据可能为综合AF管理方法提供指导，以改善 CKD的临床结局，并为未来AF和CKD患者试验的设计提供信息。

ABSTRACT Atrial fibrillation (AF) is the most common sustained arrhythmia, currently affecting >33.5 million adults world- wide, with the highest rates in North America. Chronic kidney disease (CKD) is also highly prevalent and affects 14% of the U.S. and North American population. The burden of AF is 3-fold higher in CKD and affects up to 25% of CKD patients. AF is linked to poor outcomes. Our data demonstrate that among patients with CKD, incident AF is associated with a 3-to-7-fold greater risk of heart failure (HF), acute coronary syndromes (ACS), stroke, death and progression to end-stage renal disease (ESRD) vs. CKD patients without AF. Despite the high risks associated with AF, it is unknown whether AF therapies improve outcomes in the setting of CKD. The unique pathophysiology of AF in CKD, the effects of decreased renal clearance, as well as competing risks of non-AF related death may alter the effectiveness and safety of commonly used AF medications and procedures in CKD. To our knowledge, no published studies have evaluated the collective influence of AF therapies on kidney and cardiovascular outcomes in CKD. Trials of AF therapies have largely excluded patients with CKD. Prior observational studies have several notable limitations: (1) focus only on warfarin and not a comprehensive evaluation of other AF therapies; (2) focus only on stroke and death as outcomes; and (3) inadequate consideration of interim clinical measures that may affect receipt and outcomes of AF therapies. Our overall goal is to use "real-world" contemporary data to evaluate the risks vs. benefits of various AF therapies, including medications and procedures, in adults with CKD. We will perform a comparative effectiveness analysis to delineate whether treatment of AF impacts important kidney and cardiovascular outcomes in patients with vs. without CKD. To conduct these aims, we will use the Cardiovascular Research Network (CVRN) platform to study a community-based network of ~267,000 patients with AF from two participating health care systems in California; and we will externally validate these findings in a community- based cohort of ~392,000 patients in Ontario, Canada. We will evaluate the use, response and safety of current AF therapies (including anticoagulation, rate control agents, anti-arrhythmic agents and AF-related procedures) in patients with vs. without CKD. We will perform a comparative effectiveness analysis to delineate whether treatment of AF impacts important kidney and cardiovascular outcomes in patients with vs. without CKD. The data from this study may provide guidance for an integrated AF management approach to improve clinical outcomes in CKD and inform the design of future trials of patients with AF and CKD.