FDA Gives Eagerly Awaited Update on Mortality With Paclitaxel-Coated Devices in PAD

The US Food and Drug Administration today provided an update on the late mortality signal seen with paclitaxel-coated balloons and stents in patients with PAD, but did not give any major new recommendations regarding their use.

After considering the results of its own analyses and the discussion from a 2-day advisory committee meeting held in June, the agency said clinical studies involving the devices may continue and should collect long-term safety and efficacy data.

“These studies require appropriate informed consent and close safety monitoring to protect enrolled patients,” according to the update.

Of note, the FDA also acknowledged in the updated letter that labeling modifications are in the works—a critical step that advisory panel chair, Richard Lange, MD (Texas Tech University Health Sciences Center, El Paso), had predicted to TCTMD that the FDA might take after the June meeting.

“Based on the conclusions of our analysis and recommendations of the advisory panel, the FDA is taking additional steps to address this signal, including working with manufacturers on updates to device labeling and clinical trial informed consent documents to incorporate information about the late mortality signal,” the agency said. “The FDA is also continuing to actively work with the manufacturers and investigators on additional clinical evidence development for assessment of the long-term safety of paclitaxel-coated devices.”

A higher rate of mortality with paclitaxel-coated devices gained the attention of the endovascular community when a meta-analysis led by Konstantinos Katsanos, MD, PhD (Patras University Hospital, Rion, Greece), was published in December 2018. That analysis showed that use of paclitaxel-coated balloons and stents in patients with femoropopliteal disease was associated with a greater risk of all-cause mortality at 2 years and 5 years.

The FDA first warned of the potential risk in January, following up in March with preliminary results of its own analysis showing a higher rate of death with paclitaxel-coated versus uncoated devices at 5 years. The agency said it would convene a meeting of its Circulatory System Devices panel, which took place over 2 days in June.

“The panel concluded that a late mortality signal associated with the use of paclitaxel-coated devices to treat femoropopliteal PAD was present,” the FDA said in its new update. “The panel and the FDA agreed that the magnitude of the signal should be interpreted with caution because of multiple limitations in the available data including wide confidence intervals due to a small sample size, pooling of studies of different paclitaxel-coated devices that were not intended to be combined, substantial amounts of missing study data, no clear evidence of a paclitaxel dose effect on mortality, and no identified pathophysiologic mechanism for the late deaths.”

The agency said it agrees with the panel that “additional clinical study data are needed to fully evaluate the late mortality signal.

Recommendations provided to healthcare professionals who treated patients with PAD largely mirror those released in March, with the addition of new advice stating that “physicians should explore their patients’ expectations, concerns, and treatment preferences.”

The FDA continues to recommend that patients already treated with paclitaxel-coated devices should be closely monitored and that clinicians consider the potential increase in mortality when making treatment recommendations and getting informed consent.