Implantable Monitor-Guided Anticoagulation for Non-Permanent Atrial Fibrillation

描述（由申请人提供）： 心房颤动（AF）是最常见的持续性心律异常，在美国估计影响250万至500万人，并可导致中风、心力衰竭和过早死亡。对于有房颤和其他卒中风险因素的患者，建议长期抗凝治疗以预防心内血栓形成和卒中，即使房颤不常见或短暂。这种护理标准部分基于我们无法快速识别和应对AF复发，AF复发通常是短暂和无症状的，但即使在长时间的窦性心律期间，也会使患者暴露于抗凝剂诱导出血的风险，而卒中的风险可能较低。然而，设备技术和药物治疗的最新进展有可能改变我们管理AF的方式。使用具有远程数据传输能力的小型无引线皮下植入式心脏监测器（Reveal XT”，Medtronic Inc.）能够远程持续评估患者的AF复发，即使是短暂且无症状的发作。此外，批准用于非瓣膜性AF的独特口服凝血酶抑制剂（达比加群[泰毕全]，Boehringer Ingelheim Inc.）允许在单次口服剂量的数分钟至数小时内快速起效抗凝。总之，这些进步允许仅在AF发作时进行连续AF监测和靶向抗凝，从而降低药物诱导出血的风险，同时仍能预防卒中。本初步研究的目的是评估在Reveal XT连续AF监测指导下使用达比加群进行间歇性抗凝治疗的可行性，并将数据远程传输给医疗保健提供者。该研究将从三个中心招募75名AF患者，其中1或2名其他 在心律控制干预（可能包括药物、消融或手术）后表现出持续性窦性心律的卒中风险因素。该初步研究将提供后勤方面的见解，证明可行性，并为预期的大规模临床试验（比较长期抗凝治疗与Reveal XT指导的达比加群间歇性抗凝治疗）的样本量估计生成所需数据。预计这种治疗方式可大幅减少抗凝治疗的暴露时间，从而降低出血风险，而不会增加卒中风险。从公共卫生的角度来看，这种模式转变将降低长期抗凝治疗的成本，抗凝剂相关出血的影响，包括颅内出血的破坏性后果，并改善数百万已经患有AF的患者和预计到2050年将患有该疾病的1600万患者的生活质量。如果证明上级当前的治疗方法，这种方法可以改善AF管理的一个关键方面，并沿着技术的进步为患者指导的家庭监测和治疗铺平道路。

DESCRIPTION (provided by applicant): Atrial fibrillation (AF) is the most common sustained abnormal rhythm of the heart, affects an estimated 2.5 to 5 million individuals in the US, and can lead to stroke, heart failure, and premature death. For those with AF and other stroke risk factors, chronic anticoagulation is recommended to prevent intracardiac thrombus formation and stroke even if the AF is infrequent or short-lived. This standard of care is based partly on our inability to rapidly recognize and respond to AF recurrences which can often be brief and asymptomatic, but exposes the patient to the risk of anticoagulant-induced hemorrhage even during prolonged periods of sinus rhythm where the risk of stroke is presumably low. Recent advances in device technology and drug therapy, however, have the potential to change the way we manage AF. The use of a small leadless subcutaneous implantable cardiac monitor with remote data transmission capabilities (Reveal XT", Medtronic Inc.) provides the ability to remotely and continuously evaluate a patient for AF recurrences, even episodes that are brief and asymptomatic. In addition, the release of a unique oral thrombin inhibitor approved for use in non-valvular AF (Dabigatran [Pradaxa], Boehringer Ingelheim Inc.) allows for rapid onset anticoagulation within minutes to hours of a single oral dose. Together, these advances allow for continuous AF monitoring with targeted anticoagulation only around the time of an AF episode, thereby reducing the risk of drug-induced hemorrhage while still protecting against stroke. The aim of this pilot study is to assess the feasibility of intermittent anticoagulation wih dabigatran guided by continuous AF monitoring with Reveal XT" and remote data transmission to a healthcare provider. The study will enroll 75 AF patients from three centers with 1 or 2 other risk factors for stroke who have demonstrated persistent sinus rhythm following a rhythm control intervention which may include medications, ablation, or surgery. This pilot study will provide logistical insights, demonstrate feasibility, and generate required data for sample-size estimates for an anticipated large scale clinical trial comparing chronic anticoagulation with Reveal XT"-guided intermittent anticoagulation with dabigatran. This treatment modality can be anticipated to substantially reduce the exposure time to anticoagulation therapy, thereby reducing the risk of hemorrhage without increasing the risk of stroke. From a public health perspective, such a paradigm shift would reduce the cost of long-term anticoagulation, the impact of anticoagulant-related hemorrhage including the devastating consequences of intracranial hemorrhage, and improve quality of life in a portion of the millions of patients who already have AF and the 16 million expected to have the disease by the year 2050. If proven superior to current treatment methods this approach may improve a critical aspect of AF management and pave the way, along with advances in technology, for patient- directed in-home monitoring and treatment.