FDA Panel Reviews Boston Scientific's Watchman Left Atrial Appendage Closure System

October 6, 2014—The Circulatory System Devices Panel of the US Food and Drug Administration (FDA) will meet on October 8 in Gaithersburg, Maryland, to consider new data related to the premarket approval (PMA) application for the first-of-a-kind transcatheter Boston Scientific Watchman left atrial appendage closure (LAAC) therapy, indicated to prevent thromboembolism from the left atrial appendage.

The panel will be chaired by Richard L. Page, MD, of the University of Wisconsin School of Medicine in Madison, Wisconsin. The FDA’s complete meeting materials, including FDA’s executive summary, the scheduled agenda, and the full roster of panelists and representatives are available online here. 

The FDA noted that this PMA submission was previously presented to the Circulatory Systems Devices Panel on December 11, 2013. The panel voted 13 to 1 in favor of device safety, effectiveness, and a positive benefit-risk profile. However, in February 2014, the FDA received updated follow-up data from the PREVAIL trial that showed additional ischemic strokes in Watchman patients. The updated total number of ischemic strokes in PREVAIL Watchman patients raises new questions about the effectiveness of the device and impacts benefit-risk considerations.

The updated datasets from the PREVAIL and PROTECT AF trials are the subject of this advisory panel meeting. This memorandum will summarize the FDA’s review of the data received since the previous panel meeting, highlighting areas for which it is seeking the panel’s expertise and recommendations. Panel input is especially important in addressing the question of whether a new analysis of the totality of the data has substantially changed the assessment of the benefit-risk profile of the Watchman device.

At the conclusion of the panel’s review and discussion of the new information, the agency will ask for recommendations regarding whether the data demonstrate a reasonable assurance of the safety and effectiveness of the Watchman device, and whether the probable benefits of the device outweigh the probable risks. It is critical that advisory panel members review the totality of data in making these determinations as each component of the dataset has strengths and limitations, stated the FDA.

The FDA noted that the panel will need to consider information from multiple datasets (PREVAIL, PROTECT AF, CAP, and CAP2) to determine whether the totality of the data demonstrate a reasonable assurance of device safety and effectiveness of the Watchman device.

The meeting will evaluate the device regarding the following topics: its effectiveness for reducing ischemic stroke; the role of hemorrhagic stroke; updated PREVAIL first and second primary endpoint results; major bleeding events; proposed indications for use; evaluation of the totality of the data from the Watchman trials for an overall benefit/risk assessment; and product labeling.

The panel will be asked to vote on the following questions based on each member’s expertise, the information reviewed in preparing for the meeting, and the information presented during the meeting:

1. Is there reasonable assurance that the Boston Scientific Watchman LAAC therapy is safe for use in patients who meet the criteria specified in the proposed indication?

2. Is there reasonable assurance that the Watchman LAAC therapy is effective for use in for patients who meet the criteria specified in the proposed indication?

3. Do the benefits of the Watchman LAAC therapy for use in patients who meet the criteria specified in the proposed indication outweigh the risks for use in patients who meet the criteria specified in the proposed indication?

As outlined in the FDA summary, the Watchman device consists of three components: the Watchman LAAC device; the Watchman delivery system, and the Watchman access system. LAAC device is a self-expanding nitinol structure covered by a porous polyethylene terephthalate membrane on the proximal face. The access system and delivery system allow for femoral venous access and provide a means to cross into the left atrium via the interatrial septum.

The Watchman LAAC device is packaged preloaded into the Watchman delivery system and is manufactured in five sizes corresponding to the maximum device diameter (21 mm, 24 mm, 27 mm, 30 mm, and 33 mm). The device size is intended to correspond to the maximum LAA ostium diameter. Per the instructions for use, device selection should be based on accurate LAA measurements obtained using fluoroscopy and transesophageal echocardiography from multiple angles.

After use of a standard transseptal access system to cross the atrial septum, the 12-F delivery system is placed through a 14-F access sheath. The access sheath comes in three configurations: the single curve (90º angle), double curve, and anterior curve distal tip. Upon proper positioning, the device is deployed by unscrewing the core wire from the permanent implant microscrew attachment.

Boston Scientific has proposed the following indications for use: “The Watchman LAAC device is indicated to prevent thromboembolism from the left atrial appendage. The device may be considered for patients with nonvalvular atrial fibrillation who, based on CHADS2 or CHA2DS2-VASc scores, would be recommended for warfarin therapy to reduce the risk of stroke and systemic embolism.”