Eluvia Sustains Lead Over Zilver PTX in Patients With Diabetes: IMPERIAL Subanalysis

HOLLYWOOD, FL—The gap in outcomes between the Eluvia (Boston Scientific) and Zilver PTX (Cook Medical) drug-eluting stents is especially pronounced for diabetic patients being treated for femoropopliteal disease, according to a subgroup analysis from the IMPERIAL trial. For Eluvia, safety outcomes didn’t differ between the diabetic cohort and the overall trial, but with Zilver PTX, diabetic patients fared worse than their peers.

William A. Gray, MD (Lankenau Heart Institute, Wynnewood, PA), who presented the results on Tuesday at the 2019 International Symposium on Endovascular Therapy (ISET), told TCTMD that the main message here is that for patients with diabetes and long lesions, “where we expect to see deterioration of patency outcomes, we didn’t see that at all in either group as compared to the main cohort.”

Eluvia is a novel paclitaxel-eluting stent designed specifically for the superficial femoral artery (SFA), Gray reminded ISET attendees. “As compared to the Zilver stent, which does not have a polymer, this has a biostable fluorinated polymer, which allows elution of the drug over a longer period of time, with the realization that restenosis occurs probably in the 10- to 12-month range in SFA disease, as opposed to the 3- to 4-month range in coronary disease.”

Additionally, the paclitaxel dose is lower with Eluvia than with Zilver PTX, at 0.167 µg/mm2 versus 3 µg/mm2, respectively. “Because paclitaxel is eluted over the course of nearly a year with this stent, the tissue pharmacokinetics are much different,” Gray explained. Preclinical models have suggested there is less restenotic hyperplasia with Eluvia, he said, “but without histologic evidence of worsening inflammation or issues with healing.”

To TCTMD, Gray noted that the lengthier elution time of Eluvia “is particularly relevant in a diabetic population, where restenosis may be more aggressive.”

The main IMPERIAL results were presented at TCT 2018 in San Diego, CA, with US Food and Drug Administration approval of Eluvia coming quickly thereafter.

The Gap Widens

IMPERIAL, performed at 65 centers around the world, randomized 465 patients with native SFA or proximal popliteal artery lesions with stenosis of at least 70% by visual angiographic assessment 2:1 to Eluvia or Zilver PTX. Eluvia showed better 12-month patency than Zilver PTX (86.8% vs 81.5%) in the head-to-head trial, with noninferior safety results.

About 40% of the total IMPERIAL population had diabetes, including 116 people who received Eluvia and 64 who received Zilver PTX. Within this cohort, primary patency at 12 months was 87.4% with Eluvia and 80.2% with Zilver PTX.

In terms of safety, the major adverse event (MAE) rate was 4.6% with Eluvia and 13.6% with Zilver PTX among diabetic patients (P = 0.0658), with the difference almost entirely due to clinically driven TLR, which was fourfold higher with Zilver PTX; the only other MAE was a target-limb major amputation in the Eluvia group. Stent thrombosis also was less common with Eluvia. For both endpoints, the advantage for the newer device over its predecessor was greater than what had been seen in IMPERIAL as a whole.

IMPERIAL: Safety Through 12 Months

“When we look at clinical outcomes important for patients and payers alike, we see that the distribution of Rutherford class was improved at 1 month and sustained out to 12 months [for Eluvia and Zilver PTX], as was the walking improvement questionnaire score,” Gray observed. Around 83% of patients showed no or minimal symptoms at 1 year.

“Data from this randomized controlled trial subgroup as well as in the IMPERIAL long-lesion cohort suggest that the efficacy and safety profiles of Eluvia are not affected by the challenging conditions that these at-risk populations represent,” he concluded.

IMPERIAL is slated for 5-year follow-up, Gray said to TCTMD, but he noted that the number of patients is too small to shed light on the late mortality concerns that have been raised over paclitaxel devices in PAD. “Because mortality is such an infrequent event in these trials, you need 2,000 to 6,000 patients to really understand any signal,” he explained.