WASHINGTON — Andrew Farb, MD, a medical officer at the interventional cardiology branch of FDA’s Center for Devices and Radiological Health, gave attendees at the Transcatheter Cardiovascular Therapeutics Conference an overview of how the agency currently views DES products. And he said that the long-awaited guidance concerning evaluation of new DES devices is “on the horizon” and “will be available for public comment and discussion.”

Farb told Medical Device Daily that he could not offer a precise date for publication of the guidelines, but that the document “is in the final stages of management sign-off.”

He recapped some of the conclusions of the two-day advisory panel meeting held last December, saying that the panel concluded that both of the approved stents were associated with late thrombosis but not associated with more death or myocardial infarction (MI). He reiterated that “concerns about thrombosis do not outweigh the benefits” when used on-label.

Farb said that the explanation for the lack of death and infarction, despite the later onset of thrombosis, might be that a larger pool of subjects might have shown more deaths and infarctions among those on the study devices. He offered the possible explanation that the fewer early adverse events among DES patients may have truncated any later incidents of death or infarction.

Off-label use, Farb said, “is associated with an increased risk of thrombosis, death and MI.” While dual anti-platelet therapy (DAPT) is widely perceived to be beneficial, he said it has been difficult to establish the optimal duration of DAPT. The December panel deferred to society guidelines and recommended six months for patients on the Cypher and 12 months for those who received the Taxus.

“It became clear that the application of the panel recommendations could not be evenly applied to all sponsors because one size could not fit all,” he said, and that trials for later-generation DES products completed, underway or about to start was a complicating factor. “Going forward, the approved sponsors” are urged to start “working to incorporate DAPT data” into their post-approval studies, and patients in RCTs will be followed for at least five years.

Farb proceeded to give a possible preview of the new guidance, saying that for new applications, a non-inferiority trial — rather than a superiority trial — is the design of choice, and “a new focus on safety” will be in play. Endpoints will include target lesion failure, target lesion revascularization, cardiac death, and infarction at one year. He said that trials also should describe DAPT compliance rates and actual prescription and use patterns.

FDA also wants a “reasonable portion of patients with diabetes ... and one and two-vessel disease.”

Farb said that imaging “still [plays] an important role into mechanistic insights” into the impact of a DES on stenosis but “may not be a robust measure of effectiveness” in comparisons of BMS and DES.

Patients should be enrolled consecutively, Farb said. “We’re open to nested registries to support extended indications for some patients, including patients with diabetes and no CABG indication,” but randomized controlled trials are still needed for other patient populations.

Though late stent thrombosis is rare, “it presents an ongoing concern” that FDA’s required labeling reflects, Farb said. “We cannot expect this problem to go away on its own.”

The elements needed to get a handle on the dynamics of DAPT are large sample sizes and long-term follow-up, he said, suggesting that these will answer the question of whether late stent thrombosis is “a class risk” or device-specific. However, Farb said the agency is of the opinion that an exhaustive DAPT study “will require collaboration of all the players,” including sponsors, providers and patients.

— MARK McCARTY