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SAN FRANCISCO -- The late mortality risk associated with paclitaxel-coated balloons and stents for peripheral artery disease edged down as researchers accrued more patient-level data, but still remained nonetheless, according to a new report.

With newly recovered information, the latest meta-analysis from the VIVA/NAMSA independent, patient-level data analysis showed a mortality risk (HR 1.27, 95% CI 1.03-1.58) "incrementally" lower than the last update at an FDA device panel in June (HR 1.38, 95% CI 1.06-1.80), said Krishna Rocha-Singh, MD, of Prairie Heart Institute at HSHS St. John's Hospital in Springfield, Illinois.

"This updated meta-analysis, which represents the most comprehensive analysis of available individual patient data to date, demonstrated a modest and consistent mortality signal in patients exposed to paclitaxel. However, it did not identify any explanation," Rocha-Singh told the audience at the Transcatheter Cardiovascular Therapeutics (TCT) .

It has taken 9 months for paclitaxel devices to reach this point, from a high of HR 1.93 described by investigators in a meta-analysis published in December 2018. That paper was subsequently criticized for not having patient-level data and for including studies with lots of crossover between paclitaxel and control groups.

In turn, industry stakeholders and FDA started working together to gather individual-level data with a focus on collecting vital status.

Today, the paclitaxel device issue is "by no means a done deal" and has "taken over the majority of our work load," Eleni Whatley, PhD, of the FDA, said here at TCT.

Any new application for a device containing paclitaxel -- no matter the vascular bed intended -- now has to apply with at least 5 years of data "no matter what" and with minimal loss to follow-up, she said.

Devices already on the market should remain available given that their known benefits for peripheral artery disease greatly outweigh the risks, the panel of FDA advisors said at the June meeting, but a change in labeling is warranted -- and will come as early as within the next few weeks, Whatley teased.

Regardless, several TCT panelists said they were still troubled by the lack of a mechanism that could explain these excess late-term deaths.

Mechanistic studies show there are conditions where one can get a prolonged presence or retention of drugs like paclitaxel for years, but there's no evidence this would result in toxicity, according to panelist William Gray, MD, of Lankenau Heart Institute in Wynnewood, Pennsylvania.

Ultimately, the question is what happens to paclitaxel devices in the real world, said fellow discussant Thomas Zeller, MD, PhD, of Universitäts-Herzzentrum Freiburg-Bad Krozingen in Germany. "What is the real experience? What is real life?"

He emphasized that patients included in past trials represent a highly selected group, mentioning an upcoming study (in press in European Heart Journal) using Germany insurance company data to show that paclitaxel recipients actually had reduced mortality risk.

"In my career, I've never seen the field change as dramatically over one paper as I have with this," commented Michael Jaff, DO, of Newton-Wellesley Hospital in Massachusetts, during the session.

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