Download this article's Factoid (PDF & PPT for Gold Subscribers)

Femoropopliteal lesions implanted with paclitaxel-eluting stents (PES) are almost 3 times more likely to remain open at 2 years than those treated with balloon angioplasty, even when angioplasty is backed up with provisional stenting, according to follow-up data scheduled to be published online April 9, 2013, ahead of print in the Journal of the American College of Cardiology. Patients receiving PES are also more likely to achieve event-free survival at 2 years. 

The findings were originally presented at the 23rd Annual International Symposium on Endovascular Therapy (ISET) in January 2011 in Miami, FL.

For the multinational Zilver PTX trial, investigators led by Michael D. Dake, MD, of Stanford University School of Medicine (Stanford, CA),  randomized 474 patients with symptomatic above-the-knee femoropopliteal disease of at least Rutherford class 2 to treatment with PES (Zilver PTX; Cook Medical, Bloomington, IN; n = 236) or balloon angioplasty (n = 238). In a second phase, 120 patients who had suboptimal results with angioplasty were randomized to ‘provisional’ stenting with either PES (n = 61) or a bare-metal Zilver stent (BMS; n = 59). In addition, 787 patients with more complex lesions treated with PES were enrolled in a single-arm study.

Zilver PTX is a self-expanding nitinol stent specifically designed for the superficial femoral artery (SFA). It has a polymer-free paclitaxel coating (dose 3 µg/mm²) on the abluminal side. Zilver PTX gained US Food and Drug Administration approval in November 2012 based largely on the 1-year trial results, which showed superior efficacy compared with angioplasty regardless of whether angioplasty succeeded or failed and was followed by PES or BMS stenting.

Efficacy, Safety Sustained at 2 Years

At 2 years in the randomized trial, the initial PES group fared better than the overall angioplasty group (including those who received provisional stenting) with regard to survival free from major events (amputation, clinically driven TLR, target limb ischemia requiring surgical intervention, or surgical vessel repair) as well as from worsening of Rutherford score (by 2 classes or to class 5 or 6). The most common event was TLR, which occurred in 13.4% of the initial PES group. In addition, primary patency was retained in almost 3 times as many initial PES patients as angioplasty patients. Based on Kaplan-Meier estimates, rates of sustained clinical benefit, measured by improvement over baseline in Rutherford scores, ankle brachial index, and walking impairment scores, were higher in the PES group (table 1).

 

Table 1. Two-Year Outcomes

 

The advantage of PES in primary patency was maintained across subgroups based on diabetic status, total occlusion, Rutherford class category (2-3 and 4-6), and lesion length (0-7 mm and > 7 mm; all P < 0.01).

Moreover, among the provisional stenting groups, patients who received PES had higher 2-year patency rates than those implanted with BMS (83.4% vs. 64.1%; log rank P < 0.01) and achieved higher sustained clinical benefit (83.9% vs. 68.4%; P = 0.05). On the other hand, there was no difference in patency between primary PES and provisional PES treatment (log rank P = 0.11).

In covariate analysis, smoking was the only factor affecting TLR; rates were reduced for those who had never smoked (OR 0.29; 95% CI 0.07-1.13; P = 0.02). Duration of dual antiplatelet therapy (DAPT) was the only influence on patency; rates were reduced for patients not receiving DAPT at 1 month (OR 0.36; 95% CI 0.11-1.17; P = 0.03).

In the single-arm study, the rate of freedom from TLR was similar to that of PES patients in the randomized arm. Moreover, measures of clinical benefit improved over 2-year follow-up (P < 0.01).

Benefit Sustained at 3 Years

Meanwhile, limited 3-year data presented at the Transcatheter Cardiovascular Therapeutics scientific symposium in November 2012 showed the continuing superiority of initial PES  stenting with regard to freedom from TLR (83.0% vs. 70.2% for optimal angioplasty plus provisional BMS stenting; log rank P < 0.01).

In a telephone interview with TCTMD, study coauthor Gary M. Ansel, MD, of Riverside Methodist Hospital (Columbus, OH), said the 3-year data shore up the durability of PES. “We’re going to follow patients out to 5 years, but I don’t expect any surprises,” he said. “If there were going to be a drop-off in efficacy, you would expect it to occur by the 2- or 3-year mark.”

Dr. Ansel said an underappreciated advantage of PES is that if restenosis does occur, it tends to be focal. That is important, he explained, because with focal blockage, sufficient blood flow is often maintained, thereby holding off symptoms. In contrast, with the diffuse restenosis seen in BMS, flow is more likely to fall to the point that it precipitates the return of symptoms. Moreover, he noted, diffuse in-stent restenosis is harder to treat, requiring debulking before performing a repeat procedure to achieve prolonged patency.

Zilver PTX Uptake Rapid

Since the approval of Zilver PTX, clinical uptake has been “very significant very quickly,” while use of BMS had declined “dramatically,” Dr. Ansel reported.  Although upfront costs with Zilver are higher, providers should assess overall cost-effectiveness in the context of the reduced need for repeat procedures, he observed.

One area in which application of Zilver PTX has been more “tentative,” Dr. Ansel acknowledged, is heavily calcified lesions, which may not permit full stent expansion. But diabetic patients, in whom SFA treatment has been especially problematic, appear to benefit as much as nondiabetics from the new technology, he said. And over the next 6 months, data from the FDA-mandated postmarket registry should clarify whether patients with very long lesions, who were excluded from randomized trials, also fare well with Zilver PTX, he added.

As for new technologies that might challenge Zilver PTX, Dr. Ansel pointed to bioabsorbable drug-coated stents. “That has been the natural evolution in the coronaries, and I expect to see it in the peripheral vasculature as well,” he said. Another rival therapy on the horizon is drug-eluting balloons, he said, adding that they will probably be tested first in conjunction with atherectomy in medium to long lesions to see if they can match DES in both patency and cost-effectiveness.

“But for the next couple of years, DES don’t have much of a challenge,” he concluded. 

Study Details 

The average lesion length was 65 ± 40 mm in randomized patients and 99.5 ± 82.1 mm in the single-arm study. Clopidogrel starting at least 24 hours before intervention or a procedural loading dose of 300 mg was recommended for all patients. Clopidogrel continued for at least 60 days, while aspirin use was indefinite. 

 

---

Source:
Dake MD, Ansel GM, Jaff MR, et al. Sustained safety and effectiveness of paclitaxel-eluting stents for femoropopliteal lesions: Two-year follow-up from the Zilver PTX randomized and single-arm clinical studies. J Am Coll Cardiol. 2013;Epub ahead of print.

 

 

Related Stories:

• Zilver PTX: Novel DES for Femoropopliteal Disease Encouraging at 2 Years
• Zilver Stent Seen as Welcome Addition to PAD Armamentarium
• Zilver Stent Shows High Event-Free Survival at 2 Years in Patients with PAD