Paclitaxel-Coated Devices: A Q&A With the FDA

In early January, Andrew Farb, MD, Misti Malone, PhD, and William H. Maisel, MD, MPH, of the FDA’s Center for Devices and Radiological Health, published “Drug-Coated Devices for Peripheral Arterial Disease”¹ in the New England Journal of Medicine, a response to the publication of an interim analysis of the Swedish Drug Elution Trial in Peripheral Arterial Disease (SWEDEPAD)².

CLD asked Dr. Maisel to share more about his publication and the FDA’s position regarding paclitaxel-coated device use in the lower extremities.

Why did the FDA choose to weigh in at this time?

The recent publication of the SWEDEPAD randomized, controlled trial (RCT) interim study results in the NEJM² provided important new data addressing the concern about a possible increased late mortality signal associated with paclitaxel-coated devices (PCD) used for peripheral arterial disease. Fortunately, more recent clinical studies, including the important interim analysis of the SWEDEPAD RCT, have not shown a late mortality risk associated with paclitaxel-coated devices (PCD). However, we continue to believe additional long-term follow-up data are needed because of the uncertainty around the degree of risk of late mortality in prior analyses. We felt it was important to update the public on our position in light of the availability of the new data.  

Can you reflect on how the FDA has participated in and guided this mortality signal concern? How was it effective?

The FDA is committed to fostering transparency and timely communication with the public when important safety issues arise. The FDA issued its first communication to peripheral interventionalists and vascular medicine physicians more than 2 years ago after a meta-analysis³ of randomized trials suggested a possible increased mortality rate in patients 3 years after initial implantation of PCDs for peripheral arterial disease. Our June 2019 advisory committee meeting provided an open public discussion with independent experts of the meta-analysis, the FDA’s own analysis of the pivotal randomized controlled trials conducted to support previous PCD approvals, the independent data analysis completed by the VIVA Physician Group, and data presentations by PCD manufacturers. The roadmap recommended by the FDA following the panel meeting included the analysis of additional data sources and continued enrollment and follow-up of ongoing clinical trials, while following a thoughtful, balanced benefit-risk approach to the clinical use of PCDs. This approach, based on transparency and sound, science-based recommendations, we think, has served the public and clinical community well.  

What do you advise to physicians treating lower-extremity arterial disease patients at this time?

The currently marketed devices have demonstrated a benefit in a reduction in restenosis and repeat procedures. Different patient populations have different needs and expectations regarding the benefit-risk profile of a device. The treatment decision is case-specific, and should take into account the patient’s history and characteristics of the lesion to be treated. The use of a PCD may be the best treatment for some patients, particularly those judged to be at particularly high risk for restenosis and repeat femoropopliteal interventions. 

We continue to advise health care providers to consider the recommendations in our Aug 2019 communication⁶ to health care providers, which are repeated below.
 

• Continue diligent monitoring of patients who have been treated with paclitaxel-coated balloons and paclitaxel-eluting stents.
   
• When making treatment recommendations, and as part of the informed consent process, consider that there may be an increased rate of long-term mortality in patients treated with paclitaxel-coated balloons and paclitaxel-eluting stents.
   
• Discuss the risks and benefits of all available PAD treatment options with your patients. For many patients, alternative treatment options to paclitaxel-coated balloons and paclitaxel-eluting stents provide a more favorable benefit-risk profile based on currently available information.
   
• For individual patients judged to be at particularly high risk for restenosis and repeat femoropopliteal interventions, clinicians may determine that the benefits of using a paclitaxel-coated device outweigh the risk of late mortality.
   
• In discussing treatment options, physicians should explore their patients' expectations, concerns and treatment preferences.
   
• Ensure patients receive optimal medical therapy for PAD and other cardiovascular risk factors as well as guidance on healthy lifestyles including weight control, smoking cessation, and exercise.

What recommendations would you make to paclitaxel-coated device manufacturers/distributors at this time?

Because of the demonstrated short-term benefits of the devices and the limitations of the available data, the FDA believes that clinical studies of these devices should continue and should collect long-term mortality data. Similarly, the FDA now routinely reviews longer-term data for PCDs for which market authorization is being sought when they are intended to treat patients with PAD, and the agency requests that trials capture information on adjunctive antithrombotic therapy and medications indicated for patients with atherosclerosis.

Are there particular trials the FDA will be paying close attention to going forward?

The FDA continues to review long-term clinical outcomes from patients enrolled in the pivotal PCD RCTs and data from other clinical trials, registries, and administrative databases. The FDA will continue to work with clinical investigators, medical professional societies, and the device industry to facilitate data development, and when FDA has more complete information regarding the late mortality question, we intend to update the FDA’s Aug 2019 letter to healthcare providers.

Any final thoughts?

The use of a PCD may be the best treatment for some patients, particularly those judged to be at particularly high risk for restenosis and repeat femoropopliteal interventions. Additional data are needed to further refine optimal treatment strategies for patients on the basis of their risk profile for restenosis, incorporating patient specific factors (e.g., presence of diabetes, endothelial dysfunction, increased platelet activity, or systemic inflammation) and lesion-specific factors (e.g., small-diameter vessels, long lesions, high plaque burden, or reduced distal runoff).