Warfarin Use in ESRD Patients with Atrial Fibrillation: Risks, Benefits, Behavior

描述（由申请人提供）：美国的大多数透析患者年龄>65岁，心血管风险增加。透析患者中房颤（AF）的患病率较高，但估计值差异很大（7%-27%）。此外，在界定其在这种情况下的最佳管理方面仍然存在争议。AF是血栓栓塞事件（如卒中）的重要风险因素，透析患者的风险已经增加。在一般人群中，口服华法林抗凝可显著降低这种风险，其获益已被证明明显超过出血风险增加。然而，在透析患者中，这些益处和风险之间的关系不太清楚。虽然华法林可以减少血栓栓塞事件，但透析患者即使在没有华法林的情况下也会增加出血风险。因此，透析患者华法林相关出血的风险可能更高。关于房颤透析患者的实际华法林治疗模式知之甚少，也没有在这些患者中进行华法林的试验或正式的获益-风险评估。在特定目标1中，将测量具有处方药覆盖范围的大量老年透析患者人群（N= 12，812）中的AF患病率，并定义与AF相关的临床和人口统计学特征。在特定目标2中，将评估该人群中华法林治疗AF的发生率，并定义与使用与不使用华法林相关的因素。在具体目标3中，将通过测量接受华法林治疗的AF患者与类似的未治疗AF患者相比的血栓栓塞和出血事件发生率，评估接受治疗与未治疗AF透析患者之间的结局差异。还将在来自大型国家透析提供商的单独透析患者队列中研究该目标。将使用多变量回归和倾向评分方法进行混杂控制。本可行性研究（R21）将用于开发相关证据，以帮助了解透析患者护理中常见的治疗困境。随后，将制定R 01资助申请，建议在美国范围内进行后续研究，以进一步澄清这些问题。公共卫生相关性：我们将研究严重肾功能衰竭老年患者常见的心律不齐。这种情况会增加中风的风险，而中风是可以用现有的药物预防的。由于目前还不清楚这种药物是否也是对这些透析患者的最佳治疗方法，我们的工作将研究这个问题，从而更好地照顾这些患者。

DESCRIPTION (provided by applicant): Most dialysis patients in the US are >65 years and are at increased cardiovascular risk. The prevalence of atrial fibrillation (AF) is higher in dialysis patients, but estimates vary widely (7%-27%). Further, controversy persists in defining its optimal management in this setting. AF is an important risk factor for thromboembolic events such as stroke, for which dialysis patients are already at increased risk. In the general population, oral anticoagulation with warfarin reduces this risk substantially, and its benefits have been shown to clearly outweigh an increased bleeding risk. In dialysis patients, however, the relationship between these benefits and risks is less clear. While warfarin may reduce thromboembolic events, dialysis patients are at an increased bleeding risk even in the absence of warfarin. Thus, the risk of warfarin-related hemorrhage is likely to be much higher in dialysis patients. Little is known about actual warfarin treatment patterns of dialysis patients with AF, and no trials or formal benefit-risk assessments of warfarin in these patients have been conducted. In Specific Aim 1, the prevalence of AF in a very large population of older dialysis patients with prescription drug coverage will be measured (N=12,812) and clinical and demographic characteristics associated with AF will be defined. In Specific Aim 2, the rates of warfarin treatment of AF in this population will be assessed and factors associated with its use vs. non-use will be defined. In Specific Aim 3, differences in outcomes between treated vs. untreated dialysis patients with AF will be assessed by measuring rates of thromboembolic and bleeding events in AF patients receiving warfarin, compared to similar untreated AF patients. This Aim will also be studied in a separate cohort of dialysis patients from a large national dialysis provider. Control for confounding will be performed with multivariable regression as well as propensity score methods. This feasibility study (R21) will be used to develop relevant evidence that will help inform a common treatment dilemma in dialysis patient care. Subsequently, an R01 grant submission will be developed, proposing US-wide follow-up studies to clarify these issues even further. PUBLIC HEALTH RELEVANCE: We will study a common disorder of irregular heartbeat in older patients with severe kidney failure. That condition increases the risk of stroke, which is preventable with an existing medication. Since it is not known whether this drug is also the best treatment for such patients on dialysis, our work will study this question and thus lead to better care of these patients.