September 27, 2021

The U.S. Food and Drug Administration (FDA) is informing health care providers of recent information about the potential for differences in procedural outcomes between women and men undergoing implant of a left atrial appendage occlusion (LAAO) device.

The FDA is evaluating a study published in the Journal of the American Medical Association (JAMA) Cardiology.* This analysis of real-world data in the National Cardiovascular Data Registry LAAO Registry from 49,357 patients undergoing LAAO procedures with the Watchman Left Atrial Appendage Closure device from 2016 to 2019 indicates that procedural outcomes such as major adverse events and lengthened hospital stay may be more common in women compared to men. The causes for these differences are yet to be determined.

The FDA will work with the manufacturers of approved LAAO devices to evaluate information from several sources, including premarket studies, mandated postmarket studies, and real-world data to provide additional information on this issue. Currently, the FDA believes the benefits continue to outweigh the risks for approved LAAO devices when used in accordance with their instructions for use.

Recommendations

The FDA recommends that health care providers:

• Continue monitoring patients who have been treated with LAAO devices per the current standard of care.
• Discuss the risks and benefits of all available options for stroke prevention in patients with atrial fibrillation as part of shared clinical decision-making.
• Report any adverse events or suspected adverse events experienced with the use of LAAO devices. Voluntary reports can be submitted through MedWatch, the FDA Safety Information and Adverse Event Reporting program. Device manufacturers and user facilities must comply with the applicable Medical Device Reporting (MDR) regulations. Health care personnel employed by facilities that are subject to FDA's user facility reporting requirements should follow the reporting procedures established by their facilities. Prompt reporting of adverse events can help the FDA identify and better understand the risks associated with medical devices.

Background

LAAO devices are implanted in the heart and are intended to reduce the risk of thromboembolism from the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation. The device mechanically occludes the LAA to prevent LAA thrombus from entering the systemic circulation. The manufacturers of the currently approved and marketed LAAO devices in the U.S. are Abbott Medical (Amplatzer Amulet device) and Boston Scientific (Watchman and Watchman FLX devices).

The recent article* by Darden et al. presented an analysis of 49,357 patients from the LAAO registry (41.3% women and 58.7% men) treated with the Watchman device between 2016 to 2019. The authors found a statistically significant higher rate of adverse procedural events in women compared to men including any adverse events (6.3% vs. 3.9%, p<0.001), any major adverse events (4.1% vs 2.0%, p<0.001), and hospital stay longer than one day (16.0% vs 11.6%, p<0.001). Among specific procedural adverse events, the rates of pericardial effusion requiring percutaneous drainage was 1.2% vs. 0.5% and major bleeding was 1.7% vs. 0.8% in women vs. men, respectively. Procedure-associated death was 0.3% in women and 0.1% in men.

The FDA recognizes the limitations of these data, including that the study was not randomized, only included one LAAO device (the first-generation Watchman device), and did not include longer-term outcomes beyond in-hospital events. However, the analysis provides results from a large registry of patients treated with LAAO implants in the U.S.

Registries are real-world databases that can be used to track how patients respond to particular medical devices and are one source the FDA uses to monitor postmarket device safety and effectiveness. Because the National Cardiovascular Data Registry LAAO Registry captures a large number of patients undergoing LAAO procedures, the number of patients included in this analysis was much larger than the number of patients that were included in the premarket studies of the Watchman device that supported device approval, and the premarket studies for the other approved LAAO devices. Currently, the FDA believes the benefits continue to outweigh the risks for approved LAAO devices when used in accordance with their instructions for use.

FDA Actions

The FDA is working with the manufacturers to evaluate the potential issue of sex differences in procedural outcomes with LAAO devices, including a review of available premarket and post-approval study data, and other available real-world postmarket data sets. In addition, the FDA will work with the device manufacturers, investigators, and the LAAO Registry to try to identify the causes of procedural outcome differences between women and men.

The FDA will communicate with the public if new or additional information becomes available.

Reporting Problems to the FDA

The FDA encourages health care providers to report any adverse events or suspected adverse events experienced with LAAO devices.

• Voluntary reports can be submitted through MedWatch, the FDA Safety Information and Adverse Event Reporting program.
• Device manufacturers and user facilities must comply with the applicable Medical Device Reporting (MDR) regulations.
• Health care personnel employed by facilities that are subject to the FDA's user facility reporting requirements should follow the reporting procedures established by their facilities.

Prompt reporting of adverse events can help the FDA identify and better understand the risks associated with medical devices.

Contact Information

If you have questions about this letter, contact the Division of Industry and Consumer Education (DICE).

Publication*

• Darden, Douglas et al. Sex Differences in Procedural Outcomes Among Patients Undergoing Left Atrial Appendage Occlusion. JAMA Cardiol 2021 Aug 11; e213021. Online ahead of print.