FDA rolls back warnings of death risks for paclitaxel-coated balloons, stents

After more than four years of scientific review, the FDA is rolling back warnings over cardiovascular devices and implants coated with the drug paclitaxel, saying studies have shown they do not carry an excess added risk of early death.

The agency was previously leery of some of the devices—where doses of the chemotherapy are used to help prevent the narrowing of reopened blood vessels and slow the buildup of scar tissue—and had been recommending alternatives after analyses in 2018 and 2019 highlighted potential increases in long-term mortality after two years among patients being treated for peripheral artery disease.

In its updated missive to healthcare providers this week, the agency still recommends that clinicians continue their routine monitoring of patients treated with paclitaxel-laden balloons and stents and urges them to discuss the risks and benefits of all types of treatment options for the condition.

In the time since its 2019 alert, the FDA said new data have come to light from multiple randomized, controlled trials—including studies that the agency worked with device manufacturers and others to help plan and execute. 

The updated meta-analysis also features more complete pictures of patient information and longer follow-ups, with most studies tracking participants for up to five years, according to the FDA. Longer-term follow-up is still ongoing.

Now that a review by the agency’s clinicians and statisticians has not found an association with late mortality risk, the FDA said it will work with device manufacturers to update the labeling of their products based on the latest findings.

One study, presented at the 2021 annual meeting of the American College of Cardiology, included an audit of nearly four years of real-world data that spanned more than 168,000 Medicare beneficiaries. It was unable to replicate the earlier signal of potential harm with paclitaxel-coated devices compared to bare ones. That analysis focused on peripheral artery disease patients with blockages in the thigh, spanning nearly 3,000 different healthcare facilities.

The FDA helped design that study to potentially avoid the need to conduct a large-scale, randomized trial—which could have required enrolling more than 20,000 participants with no previous exposure to paclitaxel, which in different forms is also used to treat multiple types of cancer.

The 2018 analysis that put on a spotlight on the devices’ potential risks included a total of 28 randomized trials and 4,663 participants—though only three trials and 863 cases were used to calculate all-cause death rates up to five years. It associated an increase of 7% in absolute risk and 93% in relative risk with paclitaxel-coated devices.

Between then and now, the FDA continued to approve paclitaxel-coated devices, such as Boston Scientific’s Ranger balloon in 2020. It’s designed to limit the patient’s systemic exposure to the drug, with a slim-profile balloon that carries a lower paclitaxel dose plus a coating designed to keep the drug within the surrounding tissue without spreading it to the rest of the body through the bloodstream.

More recently, the FDA approved Surmodics’ SurVeil drug-coated balloon late last month, following months of delays after agency requests for more clinical data and questions about its biocompatibility. With the balloon’s approval, Surmodics was able to claim a $27 million milestone payment from Abbott, which holds exclusive global licensing rights to the device.