Penn Study of Lariat for LAA Closure Suggests Need for FDA Reassessment of Off-Label Use of Devices

May 4, 2015—The Perelman School of Medicine at the University of Pennsylvania (Penn) announced that investigators published a study finding that the Lariat suture delivery device (SentreHEART, Inc.), which has been cleared by the US Food and Drug Administration (FDA) for soft tissue approximation during surgical procedures, is associated with a significant incidence of death and urgent cardiac surgery during its frequent off-label use for left atrial appendage (LAA) exclusion to prevent stroke in patients with atrial fibrillation.

Saurav Chatterjee, MD, et al published the study online ahead of print in the Journal of the American Medical Association: Internal Medicine. 

According to Penn, the investigators concluded that their findings merit a call for formal controlled investigations into the safety and efficacy of off-label use of the Lariat device, which has never been approved for treatment of this condition. 

The announcement noted that the Lariat device received FDA 510(k) class II clearance for soft tissue approximation in June 2006 based on stated “substantial equivalence” with other devices used to place sutures during laparoscopic surgeries or vein harvesting. However, the investigators say it appears that the Lariat device has never been used for these purposes. Instead, all reported instances of Lariat use have been for off-label LAA exclusion.

In the Penn press release, the study’s lead investigator Jay Giri, MD, commented, “The Lariat is an ingenious piece of engineering for closing the LAA, but ingenuity does not guarantee safety and efficacy. The Lariat must be assessed as a device for LAA exclusion with randomized, controlled trials before widespread use is adopted by the medical community.” Dr. Giri is Assistant Professor in the Cardiovascular Medicine Division at Penn.

Dr. Giri added, “Not only do we believe that high-quality, randomized clinical trials are necessary to determine the safety of the Lariat device for off-label procedures, but our analysis raises broader issues with the FDA 510(k) clearance protocol for medical devices. We believe there needs to be a method for reassessing the safety of a device that has been cleared for one use but is being frequently used for a different purpose in real-world practice.” 

Dr. Giri added, “The 510(k) clearance protocol is providing a regulatory loophole that allows manufacturers to avoid full safety and efficacy testing of devices cleared for one purpose, but used in practice for another higher-risk application. In addition to the Lariat, this issue could be important for other devices used in complex procedures that have been cleared through the 510(k) pathway.” 

As summarized in the Penn press release, the investigators conducted a systemic review of published reports, and an analytic review of the FDA Manufacturer and User Facility Device Experience (MAUDE) database. For the systematic review, the researchers searched PubMed, EMBASE, CINAHL, and the Cochrane Library for any reports of outcomes associated with the use of the Lariat device for LAA exclusion. 

There were seven cases of urgent need for cardiac surgery after use of the device (2.3% of the 309 procedures reviewed) and one death (0.3% of the 309 procedures), with an overall procedural success rate of 90.3%. The analytic review of the FDA MAUDE database identified five adverse event reports that noted death and an additional 23 reports of cases necessitating urgent cardiac surgery, reported the investigators.