BARCELONA, Spain – A consensus for treatment of peripheral arterial disease (PAD) emerged at last week's EuroPCR 2009 gathering here among endovascular physicians and two innovative medical devices won ringing endorsements for their novel approach to therapies based on trial results.

In a summary session confronting "Challenges in peripheral interventions," Alberto Cremonesi, MD, from Villa Maria Cecilia Hospital (Cotignola, Italy) delivered a state-of-the-art judgment for treating renal, femoral and below-the-knee arteries, rendering the following verdicts:

• Renal stent placement is declining and should continue to do so "due to the view that this procedure is effective only in selected patients, and that hypertension is frequently well managed pharmacologically."

• Femoral stent placement is of growing importance with all studies showing clear patient benefits when treated with a stent versus angioplasty and that there is a clinically supported a trend towards implanting longer stents.

• Below-the-knee stent placement is a rapidly growing area with a growing preference for balloon-only interventions and stenting being used for bail-out used in emergency cases.

In treatment of above-the-knee femoral arteries, Cremonesi said that where the current approach dictates that doctors should only revascularize after failed exercise training, more recent evidence suggests endovascular revascularization should be used as a primary treatment as it offers immediate gains in quality of life.

"All studies show stenting in general produces benefits with an immediate relief of patient complaints," he said, adding that the longer the lesion, the higher the result over time if the lesion is stented.

The two device manufacturers who won accolades for their products in PAD interventions were Cook Medical (Bloomington, Indiana), for its Zilver stent line, and Invatec (Roncadelle, Italy), for its drug-eluting balloons (DEB).

Zilver PTX kicks above-the-knee competition

The Zilver Flex 35 bare-metal stent (BMS) made its international debut at the Cook Medical exhibit during EuroPCR, but it was the future drug-eluting version of this stent, the Zilver PTX, that was winning acclaim during the conference sessions.

The nitinol stents share the same design innovation that creates a linear flexibility, as opposed to the horizontal strut strength that is a feature for coronary stents

"This stent moves, it literally flexes, which becomes important when you consider patients can have one implanted in their leg that runs 30 cm (11 inches) or more," said Andy Forster, sales manager for Cook in Europe, the Middle East and Africa.

Typically, he said, exams used in clinical studies emphasize blood flow using Doppler imaging, but angiography imaging reveals the fracturing of stents caused by metal fatigue.

A reduced fracture rate was cited in clinical studies of femoro-popliteal treatments as a benefit for this "new generation of self-expandable stents, a thinly veiled reference to the Zilver line.

Presenting results from the continuing Zilver PTX trial for above-the-knee interventions, Dirk Scheinhert from the Heart Center at the University of Leipzig in Germany, said stent integrity data for the Zilver stent platform with a mean follow up of 2.4 years showed a 1% fracture rate, a 45%improvement over previous stent data.

The Zilver PTX trial combines a randomized study of 487 patients in the U.S., Japan and Germany with a registry study of 792 patients across Europe, Russia, Canada and South Korea.

A sneak preview of preliminary data presented at the Society for Cardiovascular Angiography (SCAI) meeting in Las Vegas showed that 82% of patients treated with Zilver PTX were free from target lesion revascularization (TLR) at two years.

In Barcelona, full results presented from the study showed 78% of patients were free of adverse events of death or amputation at 24 months and Scheinhert delivered the conclusions that the Zilver platform "has excellent durability, specifically with fracture resistance, and through two years no safety concerns and favorable effectiveness."

Noting that in critical limb ischemia there is an undisputed role for femoral-popliteal intervention and good results are reinforcing a trend towards implanting longer stents (15 cm to 17 cm) to treat long lesions, Cremonesi acknowledged a question remains as to whether the quality of life benefits for patients warrant the additional costs to healthcare systems associated with the intervention.

Forster told Medical Device Daily that in Europe, where the Zilver stent is approved for sale, the company to date has won reimbursement in France and Belgium, through certain diagnostic-related groups under the German insurance system, and a majority of the 19 autonomous healthcare authorities in Spain.

"These are very, very interesting results, and what is new here is the new generation of nitinol stents," Cremonesi told MDD.

In the Zilver PTX registry study, the new Cook Medical stent is powerfully outperforming competitors at one-year follow-up showing 5% to 6% TLR among patients compared to 13% to 21% for existing products.

Balloons buoy below-the-knee treatment

"Pertinent technical development have made a drug eluting balloon the great novelty today for below-the-knee treatments," reported Cremonesi during a session at EuroPCR dedicated to "Challenges in peripheral interventions."

At the same time, during a press conference, he deflated the hopes of developers of novel laser devices for atherectomies, the removal of arterial plaque, saying "Honestly, there is not enough science to support the use of these devices, no real hard evidence."

Jean Marco, MD, professor of cardiology at Centre Cardiothoracique de Monaco, who is also the longtime course director of the Paris Course on Revascularization (the PCR in EuroPCR), went further saying, "For 30 years successful percutaneous intervention has needed to be simple, safe, and the cheaper the better. Sophisticated devices like these lasers will never work as they are neither simple, entirely safe and certainly not cheap."

The drug-coated balloon (DCB), however, is showing great promise in two small trials conducted to date making endovascular intervention below-the-knee possible where surgery is not, especially in the case of the diabetic patient, a population that makes up 80% of such cases, according to Cremonesi.

The two trials by Scheller, et al., in the coronary area and Tepe, et al., in the peripheral area, published in the New England Journal of Medicine in 2006 and 2008, respectively, contradict notions that balloons are not as effective as stenting in smaller arteries, and significantly, show that these balloons are effective to fix problems of in-stent restenosis.

"Yes, you could say it is potentially a fix for the fix," Cremonesi told MDD, though he urged caution must be exercised until larger studies are concluded.

"This is a rapidly growing area," he said, with many cath labs now entering the field and treating more, and increasingly more challenging, lesions.

The manufacturer of a paclitaxel DCB, Invatec (Roncadelle, Italy), confirmed to MDD that the company will begin enrolling patients for a larger trial, IN.PACT DEEP, later this year.

Mario Landini, vice president clinical affairs for Invatec, told MDD the strategy is to deploy the FreePac matrix that holds the paclitaxel on all its platforms.

Invatec is advancing rapidly in its product development of DCB having developed a special formulation of an agent, FreePac, to blend with paclitaxel that controls the dilution of the therapeutic in the blood flow encouraging a great uptake by the cells pressed with the balloon at the target lesion.

At EuroPCR, the company introduced the IN.PACT Admiral balloon for the superficial femoral artery (SFA) that has just received the CE mark

IN.PACT Admiral is the third DCB launched recently by Invatec, joining the IN.PACT Falcon, designed to treat coronary arteries and the IN.PACT Amphirion, designed to treat arteries below the knee.

Landini said the IN.PACT DEEP clinical trial will pit the DCB Amphirion against conventional uncoated balloons used currently in percutaneous transcatheter angioplasty (PTA) in a prospective randomized trial of 374 patients affected by critical limb ischemia (CLI) at 10 medical centers in Europe.

"It is an innovative study design for combining co-primary endpoints of clinical and angiography assessments below-the-knee and for having eligibility requirements that, while not purely an all-comers trial, are set to reflect the general CLI population," he said. "Rigorous wound-healing assessment will be another distinguishing feature."

Key to Invatec devices is the proprietary FreePac formulation that combines paclitaxel with a compound "made of a 100% natural element that can be extracted from the body, so it is absolutely hemo- and bio-compatible, said Landini.

"Where paclitaxel is a lipophilic drug, this component is hydrophilic and combining these characteristics in a specific balance and with the right coating technology for the balloon results in a balance between a necessary drug adhesion that assures you do not lose any of the drug downstream on the way to applying it to the lesion, and a necessary property for drug elution required at the lesion site that deploys the therapeutic in 30 to 60 seconds of balloon inflation," he explained.