Key data supporting the safety of paclitaxel-coated devices placed in femoropopliteal lesions has been undermined by serious errors, suggesting the mortality risk shown in a hotly debated meta-analysis may be real after all.
When that meta-analysis in the Journal of the American Heart Association turned up a for paclitaxel-coated balloons and stents (7.2% vs 3.8% crude rate) at 2 years, it sparked an FDA investigation and brought a halt to several ongoing trials.
Medtronic quickly responded with analysis from its IN.PACT Admiral drug-coated balloon trial program showing no increased all-cause mortality through 5 years compared with uncoated devices. But the company issued a press release Feb. 15, 2019 noting a programming error that led to beyond 1 year from that paper in the Journal of the American College of Cardiology.
"While a component of the recent patient-level meta-analysis will need to be updated," it said, "Medtronic has found the revised analysis still supports earlier conclusions that: there was no statistically significant difference in all-cause mortality between the IN.PACT Admiral drug-coated balloon (DCB) and plain balloon angioplasty at five years; there is no correlation between paclitaxel dosing and long-term survival in the studied population; and, there was no difference in mean nominal dose of paclitaxel between overall survival in patients treated with DCB and those who died."
The updated numbers remain to be released or published, and their impact remains to be seen.
More concerning, a was issued in Circulation on Feb. 20, 2019 reversing the mortality findings of the Zilver PTX trial, which had been cited as some of the strongest evidence for paclitaxel-coated device safety due to its long follow-up.
The paper originally showed a 5-year all-cause mortality advantage to paclitaxel-eluting stents in the femoropopliteal artery, at 10.2% versus 16.9% for the percutaneous transluminal angioplasty comparator (PTA, P=0.03).
"The authors regret that the numbers for the two groups were inadvertently reversed," the correction notice said.
In fact, the paclitaxel-coated stent had a significantly higher mortality risk ("The 5-year all-cause mortality rate was 13.6% [16.9% for the primary DES group and 10.2% for the PTA group, P=0.03], and no deaths were adjudicated as procedure or device related").
The Twitter response was stunned: "Wow," said Ved Ramnani, Head Clinical Vascular Scientist at Royal Free London NHS Foundation Trust. "Between this and the admitted error in the Medtronic DCB analysis, it's been a bad week for paclitaxel." , of Saint Luke's Mid America Heart Institute in Kansas City, Missouri, agreed.
The "paclitaxel plot thickens," said Joseph Mills, MD, of Baylor College of Medicine in Houston.