FDA panel suggests requirements for approval, further study of leadless pacemakers

In the wake of development of leadless pacemakers, the FDA’s Circulatory System Devices Panel made recommendations what should be covered in clinical trials, how postapproval studies should be designed and how physicians should be trained to implant the devices.

Two leadless pacemakers (Micra, Medtronic; Nanostim, St. Jude Medical) have had several years of clinical study and their manufacturers may seek FDA approval in the near future. A third system, being developed by Boston Scientific, is in preclinical studies.

“The object … was to evaluate, for if and when the devices might be approved, how to learn more about [them], because we can’t wait for patients who have already been enrolled to reach end-of-life for their batteries” before deciding on approval, panel chairperson Richard L. Page, MD, from the University of Wisconsin School of Medicine and Public Health, said. “This is transformative technology. It’s a masterpiece of engineering.”

The panel discussed extensively the adverse events seen in clinical studies of the Medtronic and St. Jude devices, most of which occurred in the first 2 weeks. They determined that the complication requiring the most scrutiny is cardiac perforation, which in published data to date has occurred approximately twice as often as with conventional pacemakers.

“I am concerned about cardiac perforation,” panel member David J. Slotwiner, MD, from Long Island Jewish Medical Center, New Hyde Park, New York, said. “Clearly, that is a potentially lethal complication, and it is occurring more frequently with these leadless devices than with transvenous [pacemakers]. I don’t think it’s insurmountable, but compared with the transvenous technology we have — which is an acceptable and well-established technology and applicable for most patients — I think we need to expect that this class of device has a similar complication rate.”

Panel members noted, however, that certain complications that exist with conventional pacemakers, such as those that are lead-related or pocket-related, occur rarely or never with leadless pacemakers.

The panel members endorsed the FDA staff’s position that long-term data should be collected in postmarket studies. “Acute implantation success rates for leadless pacemakers seem to be quite high, and that no device failures or complications later than 2 years have been reported, but the 5- to 10-year safety profile of the devices is not known,” the agency staff wrote in a briefing document. “FDA envisions the [post-approval studies] for the leadless pacemaker devices to be used to gain understanding of [end-of-life] issues, extraction risks/success rates and risks of co-implantation.”

The panel reached consensus that “there needs to be a robust training mechanism for physicians who are going to implant [leadless pacemakers],” Page said. “This would include the understanding that the more times you’re repositioning, possibly the greater the risk. It’s possible that patients with left bundle branch block may develop acute complete heart block while you’re manipulating that large sheath.”

The panel members suggested that leadless pacemakers receive the same indications for use as single-chamber conventional VVI or VVI(R) pacemakers.

Panel member Richard A. Lange, MD, from Texas Tech University Health Sciences Center at El Paso, said that the manufacturers and the FDA should understand that “we have to provide materials that patients can understand that tell what we do know and what we don’t know, so they can be a part of the decision-making process.”

The meeting included presentations from Medtronic and St. Jude Medical, which have leadless pacemakers being tested around the world; as well as Boston Scientific, which discussed its novel leadless pacemaker and a system designed to pair the leadless pacemaker with its subcutaneous implantable cardioverter defibrillator. – by Erik Swain

Reference:

Circulatory System Devices Panel Briefing Document.

Disclosure: The members of the FDA’s Circulatory System Devices Panel report no relevant financial disclosures.