FDA NewsPerspective

FDA advises clinicians to discuss risks of paclitaxel-coated devices with patients

The FDA today issued a series of recommendations following an advisory panel meeting on a signal of late mortality risk associated with paclitaxel-coated devices to treat peripheral artery disease, including advising clinicians to discuss extensively with patients the risks and benefits of the devices and to ensure patients are on optimal medical therapy and are following appropriate lifestyle practices.

The agency also stated clinical studies of the devices should continue.

As Healio previously reported, the FDA’s Circulatory System Devices Panel in June convened to advise the agency on the signal of late mortality risk associated with the devices — first detected in a summary-level meta-analysis and then confirmed in the FDA’s own analysis — and recommended that the devices remain on the market but that product labeling be updated to include information about the mortality signal and that clinical trials be designed to follow patients long term and to improve adjudication of deaths.

In a letter issued to health providers, the FDA stated it will continue to work with manufacturers and investigators to assess the long-term safety of the devices and to analyze additional data; it will work with manufacturers to update product labels; and it will work with investigators of ongoing clinical trials to modify informed-consent documents to include information about the mortality signal.

Ongoing clinical studies of paclitaxel-coated devices should not be stopped, according to the letter.

“Because of the demonstrated short-term benefits of the devices, the limitations of the available data, and uncertainty regarding the long-term benefit-risk profile of paclitaxel-coated devices, the FDA believes clinical studies of these devices may continue and should collect long-term safety (including mortality) and effectiveness data,” the agency stated. “These studies require appropriate informed consent and close safety monitoring to protect enrolled patients.”

In the meantime, the agency stated, clinicians should follow these recommendations:

  • Diligently monitor patients already treated with paclitaxel-coated devices.
  • Include discussion of the mortality signal during the informed-consent process.
  • Discuss risks and benefits of paclitaxel-coated devices and alternative treatments with all patients being considered for a procedure with a paclitaxel-coated device.
  • Consider that for patients at very high risk for restenosis or repeat procedures, the benefits of paclitaxel-coated devices may outweigh the late mortality risks.
  • During discussions with patients, explore patients’ expectations, concerns and treatment preferences.
  • Make sure all patients with PAD are on optimal medical therapy.
  • Make sure all patients with PAD receive guidance on lifestyle issues such as weight control, exercise and smoking cessation.
  • Report any adverse events or suspected adverse events related to paclitaxel-coated devices to the FDA’s MedWatch program.

 

The FDA today issued a series of recommendations following an advisory panel meeting on a signal of late mortality risk associated with paclitaxel-coated devices to treat peripheral artery disease, including advising clinicians to discuss extensively with patients the risks and benefits of the devices and to ensure patients are on optimal medical therapy and are following appropriate lifestyle practices.

The agency also stated clinical studies of the devices should continue.

As Healio previously reported, the FDA’s Circulatory System Devices Panel in June convened to advise the agency on the signal of late mortality risk associated with the devices — first detected in a summary-level meta-analysis and then confirmed in the FDA’s own analysis — and recommended that the devices remain on the market but that product labeling be updated to include information about the mortality signal and that clinical trials be designed to follow patients long term and to improve adjudication of deaths.

In a letter issued to health providers, the FDA stated it will continue to work with manufacturers and investigators to assess the long-term safety of the devices and to analyze additional data; it will work with manufacturers to update product labels; and it will work with investigators of ongoing clinical trials to modify informed-consent documents to include information about the mortality signal.

Ongoing clinical studies of paclitaxel-coated devices should not be stopped, according to the letter.

“Because of the demonstrated short-term benefits of the devices, the limitations of the available data, and uncertainty regarding the long-term benefit-risk profile of paclitaxel-coated devices, the FDA believes clinical studies of these devices may continue and should collect long-term safety (including mortality) and effectiveness data,” the agency stated. “These studies require appropriate informed consent and close safety monitoring to protect enrolled patients.”

In the meantime, the agency stated, clinicians should follow these recommendations:

  • Diligently monitor patients already treated with paclitaxel-coated devices.
  • Include discussion of the mortality signal during the informed-consent process.
  • Discuss risks and benefits of paclitaxel-coated devices and alternative treatments with all patients being considered for a procedure with a paclitaxel-coated device.
  • Consider that for patients at very high risk for restenosis or repeat procedures, the benefits of paclitaxel-coated devices may outweigh the late mortality risks.
  • During discussions with patients, explore patients’ expectations, concerns and treatment preferences.
  • Make sure all patients with PAD are on optimal medical therapy.
  • Make sure all patients with PAD receive guidance on lifestyle issues such as weight control, exercise and smoking cessation.
  • Report any adverse events or suspected adverse events related to paclitaxel-coated devices to the FDA’s MedWatch program.

 

    Perspective
    Gary M. Ansel

    Gary M. Ansel

    The recommendations are fair at this point. The FDA’s main mission is safety, and the current recommendations really leave it up to the physicians to take responsibility in looking at the current data and weighing the risk benefit they see for their individual patient. Realistically, this is what proceduralists should be doing for every patient they evaluate and treat.

    I am not sure what the FDA is really planning except to look at more data. I cannot conceive of a way to move to any registry or trial that could be completed or would really answer the question of mortality raised.

    We will have to continue to obtain good patient-level data from the current, in-process and planned randomized datasets to help us see the potential answer more clearly.

    Who should and should not be treated with paclitaxel-coated devices at this juncture is an important question. Though many will state that it is the patients with critical limb ischemia that should be treated, I feel that each patient has their own set of values and variables for risk and benefit. A shared decision-making process between the physician and patient will be the correct process.

    The VIVA independent patient-level data analysis that was obtained in partnership with industry continues to provide us with very important datasets, and all final data and insights are not in yet.  Certainly, if there is no dose-response that is evident, the mortality association with paclitaxel becomes much weaker. However, if there is a dose association with mortality, then we have a lot more science to figure out.

    • Gary M. Ansel, MD, FACC, FSCAI
    • Cardiology Today’s Intervention Editorial Board Member
      OhioHealth

    Disclosures: Ansel reports he consults for Boston Scientific, Cook Medical, Medtronic, Phillips, Surmodics and W.L. Gore and Associates.