麻豆传媒

GAITHERSBURG, Md. -- The late mortality signal of paclitaxel-coated devices used in peripheral artery disease (PAD) shouldn't force these balloons and stents off the market, a panel concluded at an FDA advisory committee meeting here.

Citing a totality of evidence that still weighs heavily in favor of benefits from these devices -- improved quality of life and reduced need for repeat revascularization for PAD, none of the panelists suggested restricting or eliminating access.

Yet they also judged the excess mortality risk as real, no matter the low quality of the available data. And this should be communicated carefully to healthcare practitioners and the public, the panelists said.

Todd Rasmussen, MD, of Walter Reed National Military Medical Center in Bethesda, Maryland, for example, said he accepted the finding of a late mortality risk that was first proposed last December.

"However, regarding the magnitude, I find these findings statistically significant but not practically significant. As I sit in my office and talk to my patients, I would not underestimate our patients' ability to assess and access data and make their own decision."

Patients may choose not to undergo an intervention at all if their disease is not limb-threatening and they help themselves with some exercise therapy, suggested Frank LoGerfo, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston.

"We need to learn how to communicate a short-term benefit that is certain against a long-term risk that is uncertain," said Mitchell Krucoff, MD, of Duke University School of Medicine in Durham, North Carolina.

What mechanism could be behind device-related deaths remains unclear. But just because it's not clear right now doesn't mean it doesn't exist, some suggested.

Paclitaxel has been used for decades as a chemotherapy medication. The drug kills cells at high doses; at lower concentrations, it inhibits arterial smooth muscle and endothelial cell proliferation.

"What we're seeing is maybe a trend that crescendos at 5 years," commented John Somberg, MD, of Rush University Medical Center in Chicago. "That can't be dismissed just because there's not a mechanism. Lots of things occur where subsequently they find [it]."

Krucoff recalled his years in residency before people realized what AIDS was, when infections and cancers blossomed, and how it took decades to put together that there was an immune system condition that manifests differently in different people.

In PAD, the lag time of 2 to 5 years to see an uptick in deaths among paclitaxel-coated balloon and stent recipients suggests the development of new disease, Krucoff emphasized.

Short of performing the 32,000-person trial that the FDA said it would take to exclude a mortality signal over 5 years with good statistical power, panelists suggested close collaboration among device companies and the FDA to pool their resources and speed up post-market data collection.

Accruing more 5-year data is mandatory for the understanding of the mortality risk, they added.

And as existing animal data don't provide mechanistic insights, new animal studies are "absolutely essential" going forward -- and it would be preferable that researchers get creative, added Joaquin Cigarroa, MD, of Oregon Health & Science University in Portland.

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