Paclitaxel-based Devices in PAD: Operating Under a Dark Cloud

Patrice Wendling

April 12, 2019

Professional societies in the United States and Europe are changing their stance on the use of paclitaxel-based balloons and stents to treat peripheral artery disease (PAD) after the US Food and Drug Administration's (FDA) recommendation to consider "alternative treatment options" for most patients.

In a March 15 letter to healthcare providers, the FDA reported that its preliminary review of 975 patients in three trials with 5-year follow-up data showed an approximately 50% increased mortality risk among those who received a paclitaxel-coated device compared with a bare-metal device.

The safety signal was first identified in a December meta-analysis by Katsanos et al, in which the relative risk for all-cause death with paclitaxel-based devices was increased 68% at 2 years and 93% at 5 years. The findings prompted PAD trials to be paused, positive new analyses from industry, corrections to original papers, and an international vascular leaders forum.

The Cardiovascular and Interventional Radiological Society of Europe (CIRSE) notified its members about the meta-analysis in January but took no position on the use of paclitaxel-coated devices in PAD at the time. Its recent updated position statement, acknowledging the rapidly moving landscape, notes that no mechanism has been identified for the increased mortality and that new trials may be needed to determine the veracity of the increased safety signal. It goes on to state:

"In the meantime, and until more information is available, CIRSE sees no alternative but to take the position that:

  • In the majority of patients undergoing lower limb recanalization therapies, alternatives to drug-eluting devices should be used.

  • For some individual patients at particularly high risk for restenosis, clinicians may decide that the benefits of using a paclitaxel-coated device may outweigh the risks.

  • Drug-eluting devices should only be used after a full informed-consent process that has discussed the mortality implications from the Katsanos meta-analysis.

  • All patients who have already received paclitaxel-eluting devices should be followed up to assess for a potential effect on mortality."

In response to the controversy, the Society for Vascular Surgeons (SVS) formed a Taskforce on Paclitaxel Safety in early March to facilitate a patient-level meta-analysis — something also heartily endorsed at the vascular leader's forum.

In a subsequent update, SVS president and chair of its paclitaxel task force, Kim Hodgson, MD, writes: "The cloud over paclitaxel has darkened with these new findings and advisories."

"At bare minimum, a documented discussion with the patient and a detailed description of the perceived benefits of a paclitaxel device are prudent if one is to be used in this climate," he says.

"Given the conflicting conclusions about a paclitaxel dose effect, even proceeding but choosing a lower-dose device seems unsubstantiated."

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