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Amid a flurry of data on the safety of peripheral artery disease (PAD) devices, a Medicare analysis showed no mortality risk from drug-eluting stents (DES).

Going back to the first paclitaxel-eluting stent approval (Zilver PTX) for PAD in 2012, recipients had similar mortality through a median of 2.0 years and range up to 4.1 years compared with those who got bare-metal stents (51.7% vs 50.1%, log-rank P=0.16).

That finding held with multivariable adjustment (HR 0.98, P=0.53) and was true for both those with critical limb ischemia (HR 0.97, P=0.32) and acute limb ischemia (HR 0.99, P=0.95).

These findings "suggesting the safety of these devices in routine practice" were reported by Eric Secemsky, MD, of Beth Israel Deaconess Medical Center in Boston, and colleagues, in the Journal of the American College of Cardiology.

Safety has been the big question since December, when a of randomized trials first showed 68% elevated all-cause mortality with paclitaxel-coated devices in the femoral and/or popliteal arteries. The FDA started an investigation and several trials were halted as industry and researchers scrambled for data.

"We first conceived of the idea of using available data, registry and claims data, to try to understand this relationship better as soon as that meta-analysis was published," Secemsky told 乌鸦传媒.

First, their group on ICD-10 data that could capture the drug-coated devices included in the meta-analysis -- both DES and drug-coated balloons -- showing no excess mortality compared with non-drug coated devices. But the mean follow-up was short at just over a year.

"Then we thought about how we could provide longer-term follow-up on these devices, and we realized that ICD-9 codes ... had longer follow-up but would only be useful for looking at drug-eluting stents," Secemsky said. Drug-coated balloons were approved later and never got an ICD-9 code.

Other limitations to the ICD-10 analysis included "inability to localize the lesion of interest, possible misclassification due to use of claims codes, lack of data on outpatient procedures ... the potential influence of unmeasured confounding, and the inability to determine specific causes of death," Secemsky's group noted. Also, the population was older and and sicker, with more critical limb ischemia than in the meta-analysis.

The new study included 51,456 PAD patients in the fee-for-service Medicare Provider Analysis and Review files who got first peripheral stents starting Dec. 1, 2012, when Zilver PTX was approved, and continued through Sept. 30, 2015.

Administrative codes identified peripheral DES or bare-metal stent use. Some off-label use of stents only approved for use in other vascular beds might have been mixed in, but the study likely captured mostly Zilver PTX use, Secemsky said.

Concerns about the Zilver DES had popped up again last week, when a correction notice wiped out the 5-year mortality advantage of the stent initially reported from the device's pivotal trial data. After revision, the results now show significant risk. (The error was due to a reportedly inadvertent reversal of the numbers.)

Still, Secemsky suggested that there's optimism in the field. "From all the data that we've understood, for how long we've been using these devices, I think it was hard for us to fathom that they were really causing these fatal events," he said.

He pointed to the reliability of mortality analysis in Medicare data. "We don't lose patients," he said, whereas the Zilver trial had a lot of crossover and withdrawal that could have muddied the waters.

"This is one of those situations where the data got ahead of us," Secemsky added, because such devices are usually assessed for surrogate endpoints like stent patency rather than mortality.

An as-treated analysis of the Zilver trial for mortality could help answer the issue of causality, he suggested. VIVA's partnership underway to get patient-level data from the randomized trials is "probably going to be the most definitive data we're going to see."

The VIVA Physicians' Vascular Leaders Forum and Cardiovascular Research Technologies conference will have further discussion of these issues over the next week. Watch for coverage from 乌鸦传媒.

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