The FDA’s preliminary investigation into the long-term safety of paclitaxel-coated balloons and stents revealed those devices are associated with a 50 percent higher risk of death than control devices used to treat femoropopliteal artery disease.
In its updated letter to physicians on March 15, the agency suggested alternative treatment options should be used in most cases until more data are available.
The concern over paclitaxel devices began after a meta-analysis was published in December in the Journal of the American Heart Association. That analysis, which pooled results from 28 randomized controlled trials, found relative mortality increases of 68 percent and 93 percent at two and five years, respectively, with the drug-coated devices compared to uncoated devices.
The FDA’s own preliminary analysis included three trials with at least five years of follow-up data.
“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 agency stated. “In total, among the 975 subjects in these 3 trials, there was an approximately 50% increased risk of mortality in subjects treated with paclitaxel-coated devices versus those treated with control devices (20.1% versus 13.4% crude risk of death at 5 years).”
The FDA acknowledged pooling the studies may lead to a “greater uncertainty in the results” and said the specific cause and mechanism of the higher mortality rates is unknown. Nevertheless, the agency said it would convene an advisory committee meeting of its Circulatory System Devices Panel to discuss those potential mechanisms, facilitate a discussion on the long-term mortality signal, consider modifications to U.S. clinical trials of paclitaxel products and re-examine the benefit-risk profile for these devices.
In the meantime, the FDA recommends healthcare providers continue to monitor patients who have received paclitaxel-coated devices for peripheral artery disease and discuss the risks and benefits of all available treatment options.
“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 suggested. “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.”