Dive Brief:

• FDA has alerted physicians to the potential for an increased risk of death in patients with peripheral artery disease (PAD) treated with paclitaxel-coated balloons and paclitaxel-eluting stents. The higher mortality rate was identified in patients two years following the procedure.
• The agency's letter to peripheral interventionalists and vascular medicine physicians comes after a new meta-analysis in the Journal of the American Heart Association (JAHA) observed the increased risk compared to patients treated with control devices such as non-coated balloons or bare metal stents.
• Next steps for FDA include investigating further. It currently believes the benefits of the devices continue to outweigh the risks.

Dive Insight:

Drug-coated balloons are a newer treatment option for PAD, a condition in which plaque builds up in arteries carrying blood to the legs. Medtronic, Cook Medical and C.R. Bard, now part of Becton Dickinson, are among the major U.S. makers of drug-coated balloons for PAD. FDA noted that there are a number of paclitaxel-coated balloons and paclitaxel-eluting stents approved or under study for peripheral vascular use in the United States.

In traditional balloon angioplasty, a catheter with a balloon on the end is used to widen the artery, and sometimes a stent is put in place to prevent the artery from narrowing again. Drug-coated balloons, first approved in the United States in 2014, allow medication to transfer to the wall of the artery to help prevent scar tissue from forming and re-clogging the vessel.

The JAHA meta-analysis concluded there is an increased risk of death following application of paclitaxel‐coated balloons and stents in the femoropopliteal artery of the lower limbs. The article stressed that further investigations are urgently warranted.

"There is strong evidence from statistical inference that the risk of death is 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," the authors wrote. Claudication refers to cramping pain caused by obstruction of the arteries.

The specific cause of the increased mortality rate has not yet been determined, the agency noted.

The cause is yet to be determined, but we’re reviewing all available information quickly and thoroughly and will communicate as soon as we know more.

— Scott Gottlieb, M.D. (@SGottliebFDA) January 17, 2019

FDA said it is evaluating available data, performing additional statistical analyses and working with manufacturers of the devices to better understand the issue. The review is focusing on specific causes of death, the paclitaxel dose delivered and patient characteristics, and will include an evaluation of long-term follow-up data from studies that supported approval of paclitaxel-coated balloons and paclitaxel-eluting stents. Additional statistical analyses will be performed to determine the magnitude of any long-term risks.

"In the meantime, we urge health care professionals to carefully monitor patients with peripheral arterial disease who are using these devices," FDA Commissioner Scott Gottlieb said in a statement.

The agency recommends that healthcare providers monitor patients who have been treated with the devices, discuss the risks and options with patients, and report any adverse or suspected adverse events experienced with the use of the devices.