Paclitaxel-coated products used in the peripheral arteries

Paclitaxel-coated balloons and stents are used to improve blood flow to the legs and decrease the likelihood of repeat procedures to reopen blocked blood vessels.

Medical device regulators around the world have been reviewing incidents associated with paclitaxel-coated products following the publication in December 2018 of a meta-analysis of randomised controlled trials in the Journal of the American Heart Association (JAHA) - external site.

The JAHA meta-analysis concluded there was increased risk of death following application of paclitaxel‐coated balloons and stents in the femoral and popliteal arteries of the lower limbs. It argued that further investigations were urgently warranted.

US Food and Drug Administration (FDA)

Following publication of the JAHA meta-analysis, the US Food and Drug Administration (FDA) disseminated a letter on 17 January 2019 to peripheral interventionalists and vascular medicine physicians - external site alerting them to the issue. The FDA published a further update on 15 March 2019 - external site alerting health care providers that a preliminary analysis had shown a potentially concerning signal of increased long-term mortality in study subjects treated with paclitaxel-coated products compared to patients treated with uncoated devices. On 7 August 2019 the FDA published further information - external site following its analysis of information provided to it at an advisory panel meeting in June 2019. 

Since this time, on 11 July 2023 the FDA published further information - external site following its review of the totality of the available data and analyses. 

Collaboration in an updated meta-analysis that included additional studies, more complete vital status information, and longer-term follow-up compared to prior studies was performed. In these studies, patient follow-up ranged from 2 to 5 years, with data from most studies available out to 5 years. The study data concluded that the updated randomized controlled trials (RCTs) meta-analysis does not indicate that the use of paclitaxel-coated devices is associated with a late mortality risk.

Additional analyses by the FDA of the mortality signal were also reviewed by international regulators, including the SWEDEPAD trial interim analysis, the VOYAGER PAD study, the German BARMER Health Insurance study, the U.S. Veterans Health Administration study, and the Medicare SAFE-PAD study. None of these studies, with mean or median follow-up ranging from 1.7 to 3.5 years, found a late mortality safety signal associated with paclitaxel-coated devices. Longer-term follow-up in several of these studies is ongoing.

The FDA stated:

We have determined that the data does not support an excess mortality risk for paclitaxel-coated devices. The FDA previously communicated about this topic in 2019 and is now providing updated information.

Medicines and Health products Regulatory Agency (MHRA)

The Medicines and Health products Regulatory Agency (MHRA) in the United Kingdom has also undertaken a review of the issue. Its expert advisory committee has provided advice in relation to further published recommendations for ongoing use on 4 June 2019 - external site. Their advice includes:

• Not to use these devices in routine treatment of patients with intermittent claudication
• Use these devices in patients with critical limb ischaemia is an appropriate option in accordance with NICE guidance;
• Assess the relative risks on an individual patient basis
• Ensure informed consent includes a risk-benefit discussion regarding the uncertainty in long-term outcomes; and
• Patient follow-up should be life-long.

Therapeutic Goods Administration (TGA)

There are currently 10 paclitaxel-coated products included in the Australian Register of Therapeutic Goods (ARTG) and the TGA has undertaken an appraisal of the JAHA meta-analysis and its methodology, along with other recent studies and meta-reviews. 

Review of the TGA’s data of adverse events in Australia have not shown a signal like the one described by the FDA. Adverse events reported to the TGA associated with these devices relate mostly to balloon and stent deployment issues. Most events occurred on the day of implantation and there have been no deaths reported.

Recommendations

The TGA recommends that health care providers:

• Continue to make treatment decisions based on the individual patient’s needs.
• Continue monitoring of patients who have been treated with paclitaxel-coated balloons and paclitaxel-eluting stents as per required follow up.
• When making treatment recommendations, ensure educated informed consent as part of standard process.
• Discuss the risks and benefits of all available peripheral arterial disease (PAD) treatment options with your patients. 
• Ensure patients receive optimal medical therapy for PAD and other cardiovascular risk factors as well as guidance on healthy lifestyles including weight control, smoking cessation, and exercise.^[1]

Disclaimer

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For correspondence or further information about Medical Devices Safety Update, contact the TGA's Medical Devices Branch at iris@tga.gov.au or 1800 809 361.