PHILADELPHIA, PA — A new review highlights a significant number of adverse events with the off-label use of the Lariat (SentreHEART) snare device for the exclusion of left atrial appendage (LAA) in patients with atrial fibrillation (AF).
Investigators say the time has come for formal, randomized clinical trials to test the device specifically for this indication.
"The Lariat device didn't undergo the full premarket approval [PMA] process where it was tested for that indication," senior investigator Dr Jay Giri (Perelman School of Medicine at the University of Pennsylvania, Philadelphia) told heartwire from Medscape. "It was cleared for soft-tissue approximation, which is what you'd do to clear a suture device. Now one could argue that you're suturing the left atrial appendage shut and that's soft tissue, but it's a little bit of a stretch from an indication standpoint."
The Lariat for LAA exclusion emerged through a regulatory backdoor that saw the device receive class II (intermediate-risk) clearance by the Food and Drug Administration (FDA) via the 510(k) protocol. It did not require the more rigorous PMA pathway that all class I (high-risk) devices must undergo, and given that, there is an absence of data about how well and how safely Lariat works.
"The Lariat device is an absolutely ingenious piece of engineering for closing the left atrial appendage," said Giri. "However, ingenuity does not guarantee safety and efficacy."
Lariat Appears Designed for LAA Exclusion
Publishing their findings May 4, 2015 online in JAMA Internal Medicine, the researchers identified five reports of the Lariat device for LAA exclusion in 309 individuals. Of these, the procedure was successful in 90.3% of cases, but seven individuals (2.3%) required urgent cardiac surgery and one patient died in the hospital.
The group also reviewed the FDA Manufacturer and User Facility Device Experience (MAUDE) database to compile adverse-event reports from real-world clinical practice. In total, there were 35 adverse events documented with use of the Lariat device for LAA exclusion. Of these, five reports documented pericardial effusion and death and 23 reports noted the need for urgent cardiac surgery.
The 510(k) clearance protocol does not require clinical trials to approve a device for the indication under consideration. Instead, the only burden on companies is to show that the device is "substantially equivalent" to other devices. With the Lariat device, the company had to show only that the device was equivalent to existing devices used for suture placement during surgery.
To heartwire , Giri said that "when you get into the weeds of it," the Lariat device appears to have been designed solely for the purpose of LAA exclusion. Upon 510(k) clearance, US and global patents were rapidly filed for closing the LAA with the device, he said, noting the company even emphasizes "heart" in its name. And while the design of the Lariat appears to be solely for LAA exclusion, the FDA did not have access to any data supporting that indication when the device was initially cleared.
In March, the FDA approved the Watchman (Boston Scientific) LAA closure device for the prevention of stroke in patients with AF. For the approval, the company and trial investigators took three trips before the FDA's Circulatory System Device Panel, a process that took six years and involved two major clinical trials—PROTECT-AF and PREVAIL—and a large registry. Giri suspects use of the Lariat will decline now that physicians have an FDA-approved option for LAA closure.
"There is no question there is an unmet clinical need that existed and still exists because the Watchman has its own issues, with the problem of debilitating or even life-threatening strokes in people with atrial fibrillation," said Giri. "The other problem is that the best proven way to treat them, anticoagulation, is not ideal for every single patient. Some patients can't take blood thinners, and there are some patients that don't want to take them. How do we address this unmet need? That's why there is so much interest in these left atrial appendage devices—the market is very large."
In an editorial, Dr Paul Varosy (University of Colorado, Denver) states that on behalf of patients, "we should expect for the Lariat the same rigorous evaluation by randomized trials and clinical device registries that is being undertaken for other left atrial appendage occlusion devices."
In response to the JAMA paper, SentreHEART, the maker of the Lariat device, issued a statement saying it fully supports the 510(k) process and that it is committed to clinical trials with the device. It is currently engaged in talks with the FDA and will be submitting an investigational-device-exemption (IDE) application to the agency to conduct clinical trials with Lariat in LAA closure and will seek an indication for such use.
"It is important to note that it is not unusual for device manufacturers to obtain marketing authorization for one use and then subsequently seek additional indications for use," according to SentreHEART.
Marketing Still Possible
LAA exclusion with devices such as the Lariat, Watchman, and Amplatzer Cardiac Plug (AGA Medical), which is currently undergoing testing in clinical trials, is intended to reduce stroke risk by eliminating the potential for thrombus from the left atrium. The PMA pathway, although onerous, does help the FDA verify safety and efficacy of devices before widespread utilization, according to the researchers.
Prior to their review, Giri said a rudimentary internet search of US hospitals turned up at least 60 programs promoting the utilization of the Lariat device for LAA exclusion in AF patients.
Given the way the approval process was subverted, Giri said there is no way to know if the device is safe or if it prevents stroke. Most important, there is no way to determine just how many patients have received the Lariat device for LAA exclusion. While companies are not allowed to market devices such as the Lariat for off-label uses, the message about its availability is reaching interventional cardiologists and electrophysiologists who perform the procedure.
"These are two subspecialties," said Giri. "It's not thousands and thousands of doctors around the country who need to know how to use the device. It's a smaller group of people who need to be informed about it if you're trying to get it out there. And those people can be reached in a lot of different ways that are not the classic ways the FDA considers marketing activity."
Need for Trials and the Bigger Picture
The bottom line, said Giri said, is that he would like to see the Lariat tested in a clinical trial, one that might potentially test the device against the FDA-approved Watchman. Another test would be to compare the device with anticoagulant strategies, including novel oral anticoagulants. Finally, a third trial might be to test the Lariat in patients who are not candidates for anticoagulation.
In the editorial, Varosy said that until such data are available and until the Lariat is approved by the FDA for stroke prevention in patients with AF, the use of Lariat for LAA occlusion in clinical practice "should be questioned." He believes this newest report suggests there is more than intermediate risk associated with the device.
"Because reporting to MAUDE is not mandatory and because the total number of procedures is unknown, event rates in real-world practice cannot be calculated," writes Varosy. "Real-world adverse-event rates would, however, be calculable in a clinical registry, especially if enrollment in such a device registry were mandatory."
Regarding the bigger approval picture, Giri told heartwire the 510(k) process makes sense if the device is truly low or intermediate risk. Still, once approved, such devices can be used however the physician sees fit. He said the FDA needs a better method to monitor use of an approved or cleared device so it can track how it is being used in clinical practice. He noted the agency is beginning to roll out use of a unique device identifier (UDI) that can be linked to various databases to determine how the device was used and what happened to the patient after implantation.
Giri has reported he has no relevant financial relationships. Disclosures for the coauthors are listed in the article. Varosy has reported no relevant financial relationships.
Heartwire from Medscape © 2015 Medscape, LLC
Cite this: Time to Close Lariat's Regulatory Loophole for LAA Closure in AF, Say Experts - Medscape - May 04, 2015.