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， 宽慢性肾脏疾病（CKD）也非常普遍，影响14%的美国和北美人 人口CKD患者的AF负担高3倍，影响高达25%的CKD患者。AF强烈 与缺血性中风和死亡的风险相关;这些风险在CKD患者中甚至更高。 即使在没有临床缺血性卒中的情况下，一些研究表明AF也与 所有类型的痴呆症，包括阿尔茨海默氏症和血管性痴呆症的过度风险，尽管明确的证据是， 缺乏阿尔茨海默病的特征是大脑中的神经退行性变化，包括淀粉样蛋白 证词和神经系统紊乱AF可能导致脑微梗死、脑梗死 出血和脑血流量减少，所有这些都可能促进阿尔茨海默氏病和其他 痴呆症更深入地了解AF与阿尔茨海默氏症和其他痴呆症的关系， 在CKD人群中尤其重要，在CKD人群中痴呆的发病率和患病率甚至更高 与一般人群相比，痴呆症的原因仍然难以捉摸，因此在很大程度上 未经治疗。目前，关于CKD和AF患者痴呆风险的数据有限， 对CKD患者痴呆机制的新见解。 此外，关于房颤治疗是否能减轻痴呆风险的数据在所有人群中存在矛盾 （不考虑CKD状态）。虽然有一些关于房颤治疗和痴呆风险的现有研究， 大多数都有局限性，包括（1）主要关注抗凝治疗，而不是全面评价 其他AF治疗;（2）入选选定人群，无CKD患者;（3）考虑不充分 可能影响房颤治疗的接受和结局的中期临床措施。因此， 成功治疗AF对痴呆风险的影响在很大程度上仍然未知。进一步的数据可以确定新的 用于预防和治疗痴呆症的治疗方法。 我们建议有效地利用我们独特的研究平台，包括“真实世界”的当代数据， 评估AF患者（伴或不伴CKD）的痴呆风险;以及确定是否 采用综合疗法成功治疗房颤与降低痴呆风险有关。到 在开展这项工作时，我们将对超过50万例患者进行严格的比较有效性分析， 来自加州两个参与医疗保健系统的无AF患者。该补充项目将 为理解AF和痴呆症之间的联系提供关键见解;特别是在高风险人群中， 患有慢性肾病的人。此外，预期的结果可以形成未来随机临床试验的基础。

ABSTRACT Atrial fibrillation (AF) is the most common sustained arrhythmia, currently affecting >33.5 million adults world- wide. 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 strongly associated with risk of ischemic stroke and death; and these risks are even higher in patients with CKD. Even in the absence of clinical ischemic stroke, some studies have suggested that AF is also associated with excess risks of all dementia types, including Alzheimer’s and vascular dementia, although definitive evidence is lacking. Alzheimer's disease is characterized by neurodegenerative changes in the brain, including amyloid depositions and neurofibrillary tangles. It is plausible that AF may lead to cerebral microinfarcts, cerebral hemorrhage and reduced cerebral blood flow, all which could promote Alzheimer’s disease and other dementias. Gaining a greater understanding of the association of AF with Alzheimer’s and other dementias is particularly important in the CKD population, in whom the incidence and prevalence of dementia is even higher compared with the general population; and in whom the cause of dementia remains elusive and thus largely untreated. Currently, data on the risk of dementia in patients with CKD and AF are limited and may provide new insight into the mechanisms that contribute to dementia in CKD patients. Further, data on whether treatment of AF mitigates risk of dementia are conflicting in all populations (regardless of CKD status). While there are some existing studies of treatment of AF and risk of dementia, most have limitations, including (1) a primary focus on anticoagulation and not a comprehensive evaluation of other AF therapies; (2) inclusion of selected populations and none with CKD; and (3) inadequate consideration of interim clinical measures that may affect receipt and outcomes of AF therapies. Therefore, the effects of successful treatment of AF on risk of dementia remains largely unknown. Further data could identify novel therapeutic approaches for the prevention and treatment of dementia. We propose to efficiently leverage our unique research platform that includes “real-world” contemporary data to evaluate the risk of dementia in patients with AF, with and without CKD; as well as determine whether successful treatment of AF with a comprehensive range of therapies is linked to a lower risk of dementia. To conduct this work, we will perform a rigorous comparative effectiveness analysis of >500,000 patients with and without AF from two participating health care systems in California. This proposed supplemental project will yield key insights to understanding the link between AF and dementia; particularly in the high-risk population of those with CKD. Furthermore, the anticipated results could form the basis of future randomized clinical trials.