Zilver PTX Bests Bare-Metal Stents in Largest Randomized Peripheral Endovascular Trial Ever

Reed Miller

October 13, 2010

October 13, 2010 (Washington, DC) — The Zilver PTX (Cook Group) paclitaxel-eluting peripheral stent succeeded where others have failed before, beating both percutaneous transluminal angioplasty and provisional bare-metal stenting in the largest randomized trial of a peripheral endovascular therapy to date.

Dr Michael Dake

Today at TCT 2010, Dr Michael Dake (Stanford University, Palo Alto, CA) presented one-year follow-up results of the ZILVER PTX trial, which enrolled 479 patients with moderate to severe symptomatic femoropopliteal artery disease with lesions up to 14 cm. The average lesion length was 6.6 cm. About half the patients were diabetic.

The study had two randomization protocols. First, the patients were randomized to treatment with either traditional percutaneous transluminal angioplasty (PTA) or treatment with the Zilver PTX, a nitinol, self-expanding, polymer-free, paclitaxel-eluting peripheral stent. Each patient received up to two stents.

PTA failed to restore vessel patency (defined as peak systolic velocity ratio >2) in about half the patients randomized to that group (125 total lesions), similar to the failure rates seen in previous femoropopliteal stent trials, Dake said. Failed PTA was defined as >30% residual stenosis or a >5-mm/mL pressure gradient following two to three minutes of PTA balloon inflation, as analyzed by the core lab. This so-called "nonoptimal PTA" subgroup was randomized again to a second treatment with either a bare-metal version of the Zilver stent or the Zilver PTX.

After one year, 83.1% of the stented segments treated with Zilver PTX were still patent, compared with only 32.8% of the vessels in the PTA-treated patients (p<0.01). Even when only the optimal PTAs were considered, Zilver PTX still performed much better than PTA, 83.1% compared with 65.3% (p<0.01).

In the provisional stenting group--those patients who were randomized to a bare-metal Zilver or Zilver PTX following suboptimal PTA--the 12-month patency rate was 89.9% in the Zilver PTX-treated patients compared with 73% for the bare-metal-stent–treated patients (p=0.01).

The patency rate for the Zilver PTX–treated patients was also significantly better (p<0.01) than for the group comprising both the patients whose initial PTA was optimal (126 total lesions) plus those nonoptimal PTA patients who were then randomized to bare-metal stents (63 total lesions). This "standard-of-care" group's 12-month patency rate was 67%.

Stent fractures, which plagued earlier attempts to develop a stent for the vessel below the knee, were extremely rare, only 0.9% at 12 months, and there were no clinical sequelae from the fractures. Subgroup studies with angiography, Doppler ultrasonography, and intravascular ultrasound "found no evidence of untoward effects of the drug elution or complications of the device," Dake said.

The primary safety end point of the trial was event-free survival, defined as freedom from death, amputation, target lesion revascularization, or worsening of claudication by two or more Rutherford system classes. Event-free survival at one year was 90.4% in the Zilver PTX–treated patients and 82.6% in the PTA-treated patients (p<0.01).

There were no instances of acute stent thrombosis in either the bare-metal stent patients or Zilver PTX patients, all of whom were on a dual antiplatelet regimen for at least two months postprocedure.

Dr William Gray

Commenting on the trial, Dr William Gray (New York Presbyterian Hospital, NY) pointed out that previous attempts to create a peripheral drug-eluting stent that could outperform a bare-metal version have failed. The SIROCCO II trial failed to show a difference in outcomes between femoropopliteal-disease patients treated with a sirolimus-eluting, polymer-coated stent and those treated with a bare-metal stent. Likewise, an everolimus-eluting stent failed to impress in the STRIDES trial. Gray suggested that Zilver PTX's relative success is somehow due to its polymerless design and delivery of paclitaxel instead of one of the limus drugs. ZILVER PTX, he said, "is a very important trial and potentially now groundbreaking in terms of how we can conceive of superficial femoral artery disease and popliteal treatment going forward."

Dr Hans Krankenberg (Hamburg University Cardiovascular Center, Germany) said "over the past 10 years we have made just small steps [in improving outcomes in this type of patient], so this is really a milestone study that will help us a lot in treating our patients. The problem will be in transferring the results from this trial with 6-cm lesions [to patients with longer lesions]." Krankenberg pointed out that an ongoing Zilver PTX registry of over 750 patients in Europe, Russia, Japan, and Korea, in which up to four stents are implanted per patient, is showing results similar to the ZILVER PTX randomized study. In that study, over 25% of the patients have lesions over 15 cm long and 70% have lesions greater than 7 cm long. "So overall, this medley of Zilver trials allows us to get a story that is more complete than what we can see in a single study," Dake added.

Gray acknowledged that positive results seen at 12 months might not last, as many previous stent trials have shown late catch-up of restenosis. Dr John Laird (University of California Davis Medical Center) commented that "there is a chronic injury [and] chronic irritation with stents, so there is potential for delayed restenosis, and there may be some late catch-up here. The big difference is that there's no polymer on this stent, so you don't have the polymer as a source of irritation as well, potentially tearing or falling off the stent and being a stimulus for neointimal proliferation later, so my hope would be that the late catch-up won't occur or will be less significant than with other [drug-eluting] media."

Zilver PTX is currently available in Europe under CE Mark approval. The new data are the basis of a premarket approval application that Cook submitted to the FDA in June.

Dake reported research grants and clinical trial support from Cook Group and WL Gore, consulting fees and honoraria from WL Gore and Abbott Vascular, and stock in NovoStent , Vatrix, Amaranth, CVRx, Endoluminal Sciences, REVA Medical, TriVascular, and Cytograft Tissue Engineering.