FDA Issues Cautionary ‘Dear Doctor’ Letter In Response to Study Reporting Increased Deaths with Paclitaxel-Coated Devices in PAD Treatment of Peripheral Arterial Disease with Paclitaxel-Coated Balloons and Paclitaxel-Eluting Stents Potentially Associated with Increased Mortality   

The FDA issued a Dear Doctor letter while investigating a potential safety signal with paclitaxel-coated balloons and stents used to treat peripheral artery disease. “This review will focus on the causes of death, the paclitaxel dose delivered, and patient characteristics that may impact clinical outcomes. Additional statistical analyses will be performed to clarify the presence and magnitude of any long-term risks,” the letter stated. 

The agency decided to take action following the publication of a meta-analysis in the Journal of the American Heart Association conducted by Konstantinos Katsanos and his colleagues showcasing an increased risk of death following the application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the lower limbs. The investigators of the study concluded that there was strong evidence from the statistical inference that the risk of death was significantly increased beyond the first year following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg in patients with intermittent claudication. However, the actual causes remained unknown and further clinical investigations were urgently warranted. Speaking of its clinical implications, the investigators professed that collection and reporting of longer-term follow-up (beyond 1 year) in case of all commercial clinical studies was recommended to confirm or refute the present findings. Additionally, pharmacological studies may also help understand the potential biological mechanisms behind the association of paclitaxel in the lower limbs and patient mortality. Within days, the BASIL-3, SWEDEPAD 1, and SWEDEPAD 2 investigators announced that they were pausing enrollment for these drug-coated balloon trials.

Until more information was made available, the FDA recommended healthcare providers continued monitoring patients that received these paclitaxel-coated devices, discussed the risks and benefits of these balloons and stents with patients considering them, and reported adverse events through MedWatch. Additionally, device manufacturers and user facilities would have to comply with the applicable Medical Device Reporting (MDR) regulations. Health care personnel employed by facilities that were subject to FDA’s user facility reporting requirements were supposed to follow the reporting procedures established by their facilities. Prompt reporting of adverse events could help the FDA identify and better understand the risks associated with medical devices. “Currently, the FDA believes that the benefits continue to outweigh the risks for approved paclitaxel-coated balloons and paclitaxel-eluting stents when used in accordance with their indications for use,” according to the agency.

Currently, the FDA is in the process of evaluating available long-term follow-up data to determine if there are any long-term risks associated with paclitaxel-coated products. An assessment of long-term follow-up data from studies that supported approval of paclitaxel-coated balloons or paclitaxel-eluting stents in the U.S. and other available data sets are included. This review will primarily focus on the causes of death, the paclitaxel dose delivered, and patient characteristics that may impact clinical outcomes. Additional statistical analyses will be performed to clarify the presence and magnitude of any long-term risks. “We are working with manufacturers of paclitaxel-coated balloons and paclitaxel-eluting stents to better understand this issue,” the FDA states. The educational non-profit group VIVA Physicians is hosting a forum in February to discuss the safety of these devices.