More on Mortality Risk With Paclitaxel Balloons in PAD

February 20, 2019

The continuing controversy over the safety of peripheral artery interventions with paclitaxel-delivering balloons and stents has a new chapter, with Medtronic announcing that some of its reported mortality data were omitted in error, along with a new observational study finding no safety concerns with the devices.

A meta-analysis published in December 2018 put the field on guard, sparking a broad reexamination of paclitaxel-delivering balloons and stents in peripheral interventions by suggesting a significant excess 2-year mortality risk with the devices in the femoropopliteal artery.

The report from Katsanos and associates triggered the suspension of enrollment to several randomized trials, a data review by American regulators, and a January 2019 meta-analysis of studies using Medtronic's IN.PACT Admiral paclitaxel-coated balloon, as recently chronicled by theheart.org | Medscape Cardiology.

At the time, according to news reports, officials from Medtronic, as well as from Boston Scientific, which markets the paclitaxel-coated Ranger balloon, said their internal data reviews found nothing to support the 2018 meta-analysis finding of an excess mortality.

In a February 15 press release, however, Medtronic says that "due to a programming error, mortality data were inadvertently omitted from the summary tables included in the statistical analysis" associated with safety data from its IN.PACT SFA trials.

The findings had contributed to the IN.PACT SFA meta-analysis published in January, as well as to preliminary reporting in a January press release and an interventional course underway at about the same time. The data omissions also affect the May 2018 report on 2-year outcomes from the IN.PACT Global Study, Medtronic says.

Patient deaths excluded from the presented data "were, however, previously included and reported in Medtronic's database, captured in the appropriate study exit forms, and adjudicated by an independent clinical events committee."

A revised analysis "is currently moving through the appropriate peer-review" with the published report's authors and journal editors "so the manuscripts can be appropriately corrected," the company says.

Nonetheless, "Medtronic has found the revised analysis still supports earlier conclusions" that there is no all-cause mortality difference between interventions with paclitaxel-coated and control uncoated balloons at 5 years. Nor did it see any dose-response relationship between paclitaxel and mortality."

The Latest Analysis

A review a review of femoropopliteal-artery revascularizations in 16,560 Medicare patients, published days before the latest Medtronic announcement, provided no support for an excess mortality risk associated with drug-delivering stents and balloons compared with bare-metal stents and uncoated balloons.

The rate of death from any cause over a median follow-up of 389 days was 32.5% for the 5989 patients treated with the "drug-coated devices" and 34.3% for the 10,571 patients treated with "non-drug-coated" devices (= .007 unadjusted).

The difference's significance disappeared, however, after controlling for age and sex, comorbidities, adjunctive use of atherectomy, hospital characteristics like region of the country, teaching status, and number of beds, and hospital experience with drug-coated devices.

The adjusted all-cause mortality hazard ratio for drug-coated vs non-drug-coated devices was 0.97 (95% CI, 0.91 - 1.04; = .43) in the report published online February 12 in JAMA Cardiology, with lead author Eric  A. Secemsky, MD, MSc, Beth Israel Deaconess Medical Center, Boston.

Nor were there significant differences in adjusted analyses limited to the subsets of patients with or without critical limb ischemia, or who were treated with drug-coated balloons alone or drug-eluting stents alone.

Apples and Oranges?

The authors describe a number of important differences between their cohort analysis and the December Katsanos et al report that triggered the ongoing controversy. Their study followed patients for a shorter time, "and it is possible that the risks of drug-coated devices could become apparent over greater follow-up."

Also, "our analysis only included Medicare fee-for-service beneficiaries, and this population was older and had higher rates of comorbidities, including critical limb ischemia, compared with patients in the Katsanos et al meta-analysis. The high rates of mortality observed in our study likely reflect these differences in patient characteristics."

Although the Medicare-data analysis seems to reassure that the mortality signal seen in the Katsanos et al meta-analysis might not apply to clinical practice, "there are a number of reasons why it is not easy to draw a direct comparison between the two analyses," agrees Jay Giri, MD, MPH, University of Pennsylvania and Veterans Affairs Medical Center, Philadelphia, in an accompanying editorial.

For example, the Medicare population's high baseline mortality risk "raises the concern that a relatively small absolute increase in mortality associated with paclitaxel may be washed out by competing risks of mortality."

Because of that and other differences between the populations, it's hard to say whether the current analysis should alleviate concerns raised by the Katsanos et al meta-analysis, Giri writes.

Secemsky reported no conflicts; disclosures for the other authors are in the report. Giri discloses serving on an advisory board for AstraZeneca and receiving research funds to his institution from St. Jude Medical and Recor Medical.

JAMA Cardiol. Published online February 12, 2019. Full text, Editorial

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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