Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring (REACT COM)

• Stroke rate [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  To assess the stroke rate with implantable monitor-guided intermittent anticoagulation.
• Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  To assess the overall survival rate with implantable monitor-guided intermittent anticoagulation.
• Major bleeding-free survival rate [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  To assess the major bleeding-free survival rate with implantable monitor-guided intermittent anticoagulation.
• Stroke-free survival rate [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  To assess the stroke-free survival rate with implantable monitor-guided intermittent anticoagulation.
• Quality of life assessment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  To assess the quality of life with implantable monitor-guided intermittent anticoagulation.

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 the investigators 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, release of unique oral thrombin inhibitor approved for use in non-valvular AF(Dabigatran [Pradaxa], Rivaroxaban [Xarelto]) 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 with a rapid-onset oral thrombin inhibitor guided by a continuous AF-sensing implantable cardiac monitor (Reveal XT) with remote data transmission capabilities.

Inclusion Criteria:

Patients must meet all of the following criteria:

1. Age 18 and above.

2. Patient with non-valvular, non-continuous AF in whom a rhythm control strategy has been adopted. Rhythm control strategies may include:

   1. Class I or Class III antiarrhythmic drugs
   2. Pulmonary vein isolation
   3. Post-MAZE/minimally invasive MAZE
3. Current Reveal XT implant prior to study enrollment.
4. Documented clinical history of symptomatic or asymptomatic paroxysmal, long- standing persistent or persistent AF prior to rhythm control initiation. The duration of AF must have been > or = 30 seconds and documented by 12 lead ECG, rhythm strip, or Holter ECG.
5. CHADS2 score of 1 or 2
6. Candidates for chronic anticoagulation with an FDA-approved non-Coumadin oral anticoagulant based on the discretion of the treating physician
7. Demonstrated ability to tolerate an FDA-approved non-Coumadin oral anticoagulant (i.e., Dabigatran).
8. Able and willing to provide written informed consent and willing to follow instructions, attend all required study visits, and undergo all planned tests.
9. Subject must be willing and able to discontinue oral anticoagulation for the purpose of this study.

Exclusion Criteria:

Patients should not have any of the following criteria:

1. Permanent AF
2. Any documented single AF episode lasting ≥ 1 hour per month in the two consecutive months prior to study enrollment.
3. Mechanical prosthetic valves or severe valve disease.
4. Creatinine clearance < or = 30 mg/dl
5. CHADS2 score of 0, or > 2
6. Subject deemed high risk for non-cardioembolic stroke (i.e. significant carotid artery disease) based on discretion of the investigator.
7. Individual is pregnant, nursing, or planning to become pregnant.
8. Known hypersensitivity to non-Coumadin oral anticoagulants.
9. Documented prior stroke or transient ischemic attack.
10. Reversible causes of AF (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism).

11. Conditions associated with an increased risk of bleeding:

    1. Major surgery in the previous month
    2. Planned surgery or intervention in the next 3 months.
    3. History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding
    4. Gastrointestinal hemorrhage within the past year unless the cause has been permanently eliminated (e.g. by surgery)
    5. Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days
    6. Hemorrhagic disorder or bleeding diathesis
    7. Need for anticoagulant treatment for disorders other than AF.
    8. Need for non-aspirin antiplatelet agents (i.e. Plavix) at time of enrollment
    9. Uncontrolled hypertension (SBP >180 mmHg and/or DBP >100 mmHg)
12. Recent malignancy or radiation therapy (≤6 months)
13. Anemia (hemoglobin <10g/dL) or thrombocytopenia (platelet count <100K/UL)
14. Patients who have received an investigational drug in the past 30 days or are participating in a drug study.
15. Intolerance or hypersensitivity to low dose aspirin therapy
16. Life expectancy less than the expected duration of the trial due to concomitant disease.
17. Any concomitant condition which, in the opinion of the investigator, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse).
18. Inability to comply with daily data transmission requirements.
19. Known history of isolated atrial flutter/atrial tachycardia
20. More than 10 false positive atrial fibrillation events lasting >= 30 minutes per month for two months prior to enrollment on a previously implanted loop recorder.

• National Heart, Lung, and Blood Institute (NHLBI)
• Medtronic