FDA Warns of Safety Concerns With Paclitaxel-Coated Devices


The FDA has issued a letter about a possible risk of increased mortality among patients with a type of arterial disease who have paclitaxel-coated implants.

The FDA has issued a letter to healthcare providers about the risk of increased mortality associated with vascular balloons coated with paclitaxel or stents that release the agent in the femoropopliteal artery in the leg among patients with a type of peripheral arterial disease (PAD).1

The letter follows a meta-analysis that was recently published in the Journal of the American Heart Association (JAHA; CRD42018099447), which suggested that there is a possible increased risk of death ≥2 years in patients with PAD treated with these devices compared with control devices, which consist of noncoated balloons or bare metal stents. The specific cause of this mortality observation has not yet been determined, the agency stated.

In the letter, the agency recommended physicians monitor patients who have been treated with the coated balloons and eluting stents, and discuss the benefits and risks of all available therapies for patients with PAD. The FDA also said that, currently, the benefits continue to outweigh the risks when the devices are used as indicated. Additionally, all observed or suspected adverse events associated with these devices should be reported.

The paclitaxel-coated balloons and paclitaxel-eluting stents are approved by the FDA to treat obstructed lesions in arteries of the legs. Mechanistically, the balloon and stent operate to open the obstructed vessel, and paclitaxel is released from the balloon or stent to prevent scar tissue formation in the blood vessel that can re-obstruct the artery.

Intravenous paclitaxel is approved by the FDA for indications in breast cancer, ovarian cancer, non—small cell lung cancer, and Kaposi’s sarcoma.

The FDA also noted in a press release that it is currently evaluating the available long-term follow-up data to determine whether there are any associated long-term risks with paclitaxel-coated products. Additional statistical analyses are also being conducted to identify the magnitude and presence of any long-term risks.

In the JAHA study, investigators conducted a systemic review and meta-analysis of 28 randomized controlled trials of paclitaxel-coated devices in the femoral and/or popliteal arteries with a primary endpoint of all-cause patient death. Risk ratios and risk differences were pooled with a random effects model, and 4663 patients (89% intermittent claudication) were analyzed.

Of 28 trials with 4432 cases, the all-cause patient death at 1 year was similar between paclitaxel-coated devices and the control arm at 2.3% versus 2.3% (Risk ratio, 1.08; 95% CI, 0.72-1.61). At 2 years, the all-cause death at 2 years—which was 12 trials and 2316 cases—was significantly higher in the paclitaxel arm (7.2%) than in the control arm (3.8%; risk ratio, 1.68; 95% CI, 1.15-2.47; number-needed-to-harm, 29 patients [95% CI, 19—59]).

Up to 5 years, the all-cause death of 3 trials and 863 cases continued to be higher in the paclitaxel-coated arm (14.7%) versus the control arm (8.1%; risk ratio, 1.93; 95% CI, 1.27-2.93—number-needed-to-harm, 14 patients [95% CI, 9—32]).

Moreover, meta-regression showed a significant link between exposure to paclitaxel (dose-time product) and absolute risk of death (0.40.1% excess risk of death per paclitaxel mg-year; P<.001). A trial sequential analysis excluded false-positive findings with 99% certainty (2-sided a, 1.0%).

The study investigators concluded in the article that further investigations are warranted.


  1. Treatment of Peripheral Arterial Disease with Paclitaxel-Coated Balloons and Paclitaxel-Eluting Stents Potentially Associated with Increased Mortality - Letter to Health Care Providers. FDA. Published January 17, 2019. https://bit.ly/2W0wr3B?rel=0". Accessed January 17, 2019.
  2. Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg: a systematic review and meta-analysis of randomized controlled trials. JAHA. 2018;7:e011245. doi: 10.1161/JAHA.118.011245.
© 2024 MJH Life Sciences

All rights reserved.