The WATCHMAN (Boston Scientific, Marlborough MA) left atrial appendage (LAA) occlusion device has recently been approved for reimbursement by the Centers for Medicare & Medicaid (CMS). Despite many other contenders, and even an approved general tissue closure device utilized to close the LAA, this is the first specific LAA occlusion device approved by the CMS. It is important to note the differences between the CMS approval and the Food and Drug Administration (FDA) approval in March of 2015. In the FDA approval the device was restricted to those patients who were deemed suitable for long term warfarin, remaining true to the indications for enrollment in the clinical trials. The CMS removes that restriction, and if fact states that the device is an option for those patients deemed not suitable for long term anticoagulation (but could still tolerate short term warfarin).

The WATCHMAN, and other similar devices, was conceived to reduce thromboembolism in patients with atrial fibrillation (AF) and who had an increased risk of bleeding on anticoagulation. The LAA is believed to be the source of thromboembolism in patients with AF.¹ Although mechanistically reasonable, there is not universal agreement that the LAA is the source of all thromboembolism in patients with AF. In fact, there is data that the incidence of left atrial thrombus outside the LAA is 11% in non-valvular AF and increases to > 50% in valvular AF.² Thus, LAA occlusion, even if 100% safe and effective would not prevent all thromboembolic events.

Based on a number of randomized control trials, there is strong evidence that systemic anticoagulation reduces thromboembolism.³ Indeed, for all the novel anticoagulants the comparator is warfarin and not placebo; however, anticoagulation does not eliminate the risk. The risk of stroke can be estimated with the CHA₂DS₂-VASc score, a combination of congestive heart failure, hypertension, age, diabetes, vascular disease, and sex. Yet, many of the risk factors for thromboembolism are the same as those for the risk of a major bleed. For example, one of the most utilized bleeding risk scores is the HAS-BLED, a combination of hypertension, abnormal renal and liver function, stroke, prior bleed, labile international normalized ratio (INR), elderly, and abuse of drugs or alcohol.⁴ Thus, it is often the case that individual patients will be at high risk of stroke and major bleeds.

The PROTECTion in Patients With Atrial Fibrillation (PROTECT-AF) trial was the first randomized trial of LAA occlusion devices. In the trial involving 707 patients with a mean CHA₂DS₂-VASc of 3.2, the WATCHMAN device was successfully implanted and was noninferior to warfarin in the prevention of thromboembolism, but at a significant cost of serious complications.⁵ After failure to win FDA approval, and with the FDA mandating a second RCT, the PREVAIL (Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trial began. The PREVAIL trial enrolled 461 patients with a mean CHA₂DS₂-VASc of 3.8, and demonstrated that decreased rates of complications compared to PROTECT-AF were possible; however, there was no particular clinical advantage for the WATCHMAN compared to warfarin.⁶ Enrollment in these two trials, by necessity, included the lack of a contraindication to warfarin, as long term warfarin was the comparator arm.

The CMS approval is quite specific in its criteria for implantation of the device in patients with AF (https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=281&bc=ACAAAAAAAgAAAA%3d%3d&). These criteria are summarized below:

1. CHA₂DS₂-VASc of ≥ 3 or CHADS2 ≥ 2.
2. Formal shared decision utilizing an independent, non-interventional physician whose opinion must be written in the medical record.
3. Suitability for short-term warfarin, but deemed unable to take long-term anticoagulation.
4. Procedure must be performed in a hospital with an established structural heart disease or electrophysiology program.
5. Procedure must be performed by an interventional cardiologist, electrophysiologist or cardiovascular surgeon, who must have received formal training by the manufacturer, have performed ≥ 25 transeptal procedures, and continue to perform ≥ 25 transeptal procedures, including 12 of which are LAA occlusion, over a two year period.
6. Patient is enrolled, and physicians and hospital participate in a prospective, national, audited registry for at least four years from the time of implantation.

These criteria importantly differ from FDA criteria in that the inclusion criteria include those believed not to be candidates for long-term anticoagulation. However, they are very much more clinically based in that the patients who receive these devices should only be those with an increased risk of bleeding with long-term anticoagulation. Those patients who can be managed with warfarin or one of the direct anticoagulants should not have a WATCHMAN placed, but rather should be anticoagulated. There are real risks of the procedure and we still do not know the efficacy and safety over long-term follow-up. Life-years observed in WATCHMAN patients are only a fraction of those on anticoagulation. Thus, the authors of this Expert Analysis believe that the CMS indication is more sound than that of the FDA, and at this time the authors do not favor implantation of the WATCHMAN as an elective replacement for anticoagulation.

What next? A 2015 American College of Cardiology/Heart Rhythm Society/ Society for Cardiovascular Angiography and Interventions societal overview appropriately recommended ongoing prospective registries of LAA occlusion, particularly with regard to patient selection and outcomes.⁷ We are quite pleased with the recent CMS decision on WATCHMAN mandating the enrollment of patients into such a prospective registry. We would argue that such a registry should also be established and mandated for all LAA occlusion devices, including those currently in use and future devices or techniques. Coverage of the WATCHMAN will in all likelihood be expanded to third party payers over time. It would be reasonable for these payers to adopt the CMS criteria, including the mandate to participate in the prospective registry.

Until we obtain more short-term data on decreasing procedural complications and long-term data on efficacy, it would be reasonable to be cautious in patient and physician selection for the WATCHMAN.⁸ There are concerns about the learning curve of implantation; serious complications (pericardial effusion, stroke, device embolization) were observed in nearly 8% of the initial PROTECT-AF patients, dropping to 3.7% for the patients enrolled in the continued access protocol, and to 2% for the PREVAIL trial. Although thromboembolism was low in both groups in the PREVAIL trial, non-inferiority was not achieved for the WATCHMAN. In other words, patients randomized to warfarin did better.

We are entering a new era in the options for prevention of thromboembolism for patients with AF. Anticoagulation agents have expanded over the last several years, and now include agents which have been demonstrated to be safer and more effective than warfarin in large clinical trials. Whether LAA occlusion devices will follow a similar trajectory to these direct anticoagulants is not clear, and more data is necessary before a widespread expansion is warranted.

References

1. Johnson WD, Ganjoo AK, Stone CD, Srivyas RC, Howard M. The left atrial appendage: our most lethal human attachment! Surgical implications. Eur J Cardiothorac Surg 2000;17:718-22.
2. Mahajan R, Brooks AG, Sullivan T, et al. Importance of the underlying substrate in determining thrombus location in atrial fibrillation: Implications for left atrial appendage closure. Heart 2012;98:1120-6.
3. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014;130:2071-104.
4. Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: The HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol 2011;57:173-80.
5. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial appendage closure: Results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation 2011;123:417-24.
6. Holmes DR, Jr., Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial. J Am Coll Cardiol 2014;64:1-12.
7. Masoudi FA, Calkins H, Kavinsky CJ, et al. 2015 ACC/HRS/SCAI left atrial appendage occlusion device societal overview. Heart Rhythm 2015;12:e122-36.
8. Estes NA, 3rd. Left Atrial Appendage Closure for Stroke Prevention in AF: The Quest for the Holy Grail. J Am Coll Cardiol 2015;66:2740-2.

Keywords: Aged, Alcohols, Angiography, Anticoagulants, Atrial Appendage, Atrial Fibrillation, Device Approval, Diabetes Mellitus, Electrophysiology, Heart Failure, Hypertension, Insurance, Health, Reimbursement, International Normalized Ratio, Liver, Medicaid, Medical Records, Medicare, Patient Selection, Pericardial Effusion, Pharmaceutical Preparations, Prospective Studies, Registries, Risk Factors, Stroke, Surgeons, Thromboembolism, Warfarin, United States Food and Drug Administration

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