The US Food and Drug Administration (FDA) is warning physicians of a “potentially concerning signal” of increased long-term mortality in patients who have received a paclitaxel-coated balloon or paclitaxel-eluting stent to treat peripheral arterial disease (PAD) in the femoropopliteal artery, the agency said March 15 in an updated letter to healthcare providers.
While the analyses are ongoing, “because of this concerning safety signal, we believe alternative treatment options should generally be used for most patients while we continue to further evaluate the increased long-term mortality signal and its impact on the overall benefit-risk profile of these devices,” the FDA advised.
The warning letter follows a vascular leaders forum convened earlier this month to address the issue, in which FDA officials acknowledged that the safety signal persisted in their initial investigation of the devices.
On January 17, as reported by Medscape Medical News, the FDA notified healthcare providers about the potential for increased long-term mortality with paclitaxel-coated balloons and stents used to treat PAD identified in a meta-analysis of randomized trials.
That analysis, published in the Journal of the American Heart Association , reported a 68% relative risk increase in all-cause death with paclitaxel-coated balloons and stents beginning at 2 years that increased to 93% at 5 years.
The FDA has been conducting a preliminary analysis of long-term follow-up data of the premarket randomized trials for paclitaxel-coated products indicated for PAD.
Each of the three trials with 5-year follow-up data showed higher mortality in patients treated with paclitaxel-coated products than in their peers treated with uncoated devices. In total, among the 975 patients in these three trials, there was about a 50% increase in risk of mortality in patients treated with paclitaxel-coated devices compared with those treated with control devices (20.1% vs 13.4% crude risk of death at 5 years), the FDA said.
The data should be interpreted with caution for several reasons, the FDA said. “First, there is large variability in the risk estimate of mortality due to the limited amount of long-term data. Second, these studies were not originally designed to be pooled, introducing greater uncertainty in the results. Third, the specific cause and mechanism of the increased mortality is unknown,” the FDA said.
The FDA intends to conduct additional analyses to determine whether the benefits continue to outweigh the risks for approved paclitaxel-coated balloons and paclitaxel-eluting stents when used as currently indicated.
In addition, they will convene an advisory committee meeting of the circulatory system devices panel to reexamine the benefit-risk profile of this group of devices and consider modifications to ongoing and future US clinical trials evaluating devices containing paclitaxel, among other topics.
For now, the FDA recommends that healthcare providers consider the following:
Discuss the risks and benefits of all available PAD treatment 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 said
Providers are asked to report any adverse events or suspected adverse events experienced with these devices through MedWatch, the FDA Safety Information and Adverse Event Reporting program.