Zilver PTX Trial Shows Benefits of DES in Treating SFA Disease

September 24, 2010—Principal investigator Michael D. Dake, MD, presented 1-year results from an evaluation of the Zilver PTX paclitaxel-eluting stent (Cook Medical, Bloomington, IN) in a late-breaking trial session at the annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium in Washington, DC.

As reported in the conference’s newspaper, TCT Daily, the data demonstrated the clinical benefit of using the paclitaxel-eluting stent to treat symptomatic peripheral artery disease (PAD) in the above-the-knee femoropopliteal artery compared to balloon angioplasty with provisional stenting using the bare-metal equivalent of the Zilver PTX. The Zilver PTX is a self-expanding nitinol stent specifically designed for the superficial femoral artery (SFA). The device features a polymer-free paclitaxel coating (dose = 3 µ/mm²) on the abluminal side of the stent struts.

The trial began in 2005 and reached its primary endpoints in 2010. It is a prospective randomized trial with 479 patients (Zilver PTX, n = 241; angioplasty, n = 238) at 55 trial sites in the United States, Japan, and Europe. In the angioplasty group, half of the patients had suboptimal angioplasty and underwent secondary randomization to provisional stenting with a Zilver PTX (n = 61) or bare-metal Zilver (n = 59).

In the study, 12-month patency rates were 83.1% with the Zilver PTX and 67% with angioplasty and bare-metal stenting. In a head-to-head comparison of provisional stenting, the patency rates at 12 months were 89.9% with the Zilver PTX and 73% with the BMS, showing that the drug effect was significant. Safety endpoints in the trial were also met.

In a per-protocol analysis, the primary safety endpoint of 12-month event-free survival from death, amputation, target lesion revascularization, or worsening Rutherford score (by two classes or to class 5 or 6) was improved by Zilver PTX over angioplasty (90.4% vs 82.6%; P < .01). The difference began to emerge at approximately 6 months. Stent fractures were rare in both Zilver PTX and BMS patients at on overall rate of 0.9% through 12 months, and no fractures resulted in clinical sequelae.

Based on intention to treat, the primary efficacy endpoint of 12-month primary patency on duplex ultrasonography (peak systolic velocity ratio < 2) or angiography if available (diameter stenosis < 50%) was higher for Zilver PTX than for angioplasty. Patency was slightly improved in the subgroup of patients who had optimal angioplasty but still less than in Zilver PTX. Patients who underwent standard of care angioplasty with provisional BMS also had significantly poorer patency rates with a 49% relative reduction in restenosis with the Zilver PTX (83.1%, Zilver PTX vs 32.8%, angioplasty; P < .01; 83.1% vs 65.3%, optimal angioplasty only; P < .01; 83.1% vs 67%, optimal angioplasty or suboptimal angioplasty plus BMS; P < .01).

To examine the drug effect, the investigators conducted a head-to-head comparison of secondary randomization to provisional stenting with Zilver PTX or BMS and found 12-month patency rates of 89.9% and 73%, respectively (P = .01), representing a 63% relative reduction in restenosis with DES treatment.

Dr. Dake advised that limitations of the trial include its reliance on duplex ultrasonography rather than angiography in 85% of the cohort, the relative high acute failure rate for angioplasty, and a study design that stipulated lesion length ≤ 14 cm and excluded in-stent restenosis.

"This is an important step toward reducing amputations, bypass, and repeat intervention surgeries in patients with PAD, which is very difficult to treat," said Dr. Dake in a statement from the Cardiovascular Research Foundation, the sponsor of the TCT meeting.

In the TCT Daily, William A. Gray, MD, commented on the trial, noting that these results follow soon after two DES studies that have failed to show efficacy at 12 months: SIROCCO, which tests a sirolimus-eluting stent, and STRIDES, which tests an everolimus-eluting stent. Both of the stents tested in those trials had durable polymers. Dr. Gray questioned the possible mechanisms for the observed efficacy, pointing out that the Zilver PTX eluted paclitaxel and has no durable polymer. He also noted that lesion lengths are typically 20 to 30 cm in clinical practice. "That aside," he said, "this is a very important trial and potentially groundbreaking in terms of how we conceive of SFA and popliteal treatment going forward."

Hans Krankenberg, MD, a TCT discussant, also praised the trial as a milestone but stated that the challenge is to transfer the results from a trial with 6-cm lesions. The results suggest that the findings might be generalizable to real-world treatment, Dr. Krankenberg told the TCT Daily.