Implantable Monitor-Guided Anticoagulation for Non-Permanent Atrial Fibrillation

描述(由申请人提供)： 房颤(AF)是最常见的持续性心脏节律异常，在美国估计有250万至500万人受到影响，并可导致中风、心力衰竭和过早死亡。对于有房颤和其他中风危险因素的患者，推荐使用慢性抗凝来防止心内血栓的形成和中风，即使房颤很少发生或持续时间很短。这种标准的护理部分是基于我们无法快速识别和应对房颤的复发，房颤的复发通常是短暂的和无症状的，但即使在卒中风险较低的长时间窦性心律期间，患者也面临着抗凝剂诱导出血的风险。然而，设备技术和药物治疗的最新进展有可能改变我们处理房颤的方式。使用具有远程数据传输能力的小型无铅皮下植入式心脏监测器(Display XT“，Medtronic Inc.)提供远程和持续评估患者房颤复发的能力，即使是短暂和无症状的发作也是如此。此外，一种独特的口服凝血酶抑制剂的释放被批准用于非瓣膜性房颤(Dabigatran[Pradaxa]，Boehringer Inglheim Inc.)可在单次口服后数分钟至数小时内迅速起效抗凝作用。总而言之，这些进步使得只有在房颤发作前后才能通过靶向抗凝进行持续的房颤监测，从而降低了药物引起出血的风险，同时仍然可以预防中风。这项先导性研究的目的是评估Dabigatran间歇性抗凝的可行性，该方法是在持续房颤监测的指导下进行的，并将数据远程传输到医疗保健提供者。这项研究将从三个中心招募75名房颤患者，另有1到2名 经节律控制干预后出现持续性窦性心律的中风的危险因素，可能包括药物、消融或手术。这项先导性研究将提供后勤方面的见解，论证可行性，并为预期的大规模临床试验的样本量估计提供所需的数据，该试验将比较慢性抗凝与REVIDESS XT“引导的间歇性抗凝与达比加兰。可以预期，这种治疗方式可以显著减少接受抗凝治疗的时间，从而在不增加中风风险的情况下降低出血风险。从公共卫生的角度来看，这种范式的转变将降低长期抗凝的成本，降低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房颤的患者和预计到2050年将有1600万人患有房颤的患者的生活质量。如果证明优于目前的治疗方法，这种方法可能会改善房颤管理的一个关键方面，并随着技术的进步，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.