After a preliminary analysis of long-term follow-up data, the FDA has found that paclitaxel-coated devices used to treat femoropopliteal artery disease are linked with up to approximately a 50% increased risk in mortality.
“While the analyses are ongoing, our preliminary review of this data has identified a potentially concerning signal of increased long-term mortality in study subjects treated with paclitaxel-coated products compared to patients treated with uncoated devices,” the FDA stated in an updated letter.
Three trials with 5-year follow-up data were included in the analysis, with 975 participants across the three trials. Among those participants, there was an approximately 50% increased risk of mortality in those treated with paclitaxel-coated devices compared with those treated with control devices (20.1% versus 13.4% crude risk of death at 5 years).
As a result of the concerning mortality signal, the FDA will hold an Advisory Committee meeting of the Circulatory Systems Devices panel with the goal of having a transparent and unbiased discussion on the mortality risk, as well as discussing potential biological mechanisms and considering updates to US clinical trials in terms of informed consent and adjudication for drug-related adverse events and deaths.
The FDA plans to announce the details regarding the time and location of the Advisory Committee meeting in the coming weeks.
The FDA urged caution in interpreting the mortality data at this stage though, as there is large variability in the risk estimate of mortality resulting from limited long-term data. Additionally, the studies examined were not designed to be analyzed together, and the mechanism responsible for increased mortality is not known.
Until further information is known, the FDA recommends that health care providers continue monitoring patients treated with paclitaxel-eluting devices, consider the possibility of long-term mortality risk as part of the informed consent process and treatment decisions, and discuss benefits and risks of all available PAD options with patients.
“For most patients, alternative treatment options to paclitaxel-coated balloons and paclitaxel-eluting stents should generally be used until additional analysis of the safety signal has been performed,” the FDA wrote. “For some individual patients at particularly high risk for restenosis, clinicians may determine that the benefits of using a paclitaxel-coated product may outweigh the risks.”