The Xience V DES by Abbott Vascular may be launched in Europe in the coming year.
Author’s Note: EuroPCR definitely has its own flare. The meeting combined education, exhibits and divertissement.
As meetings go, EuroPCR 2006 was definitely different than meetings that take place in the U.S. Drug-eluting stents (DES) dominated the coronary sessions. To put things into perspective, each year EuroPCR organizers collect data from “high-impact” peer reviewed journals to create a booklet of randomized trials. DES made up 36 pages of this booklet.
The organizers also publish an endovascular angioplasty product catalog each year as well. There were 27 companies showcasing their stent technologies in the coronary angioplasty section of the catalog. In contrast, the next largest segment was angioplasty balloon technologies, for which there were 18 companies showcasing their wares.
Although DES technologies appeared to dominate the coronary sessions, in terms of news and discussions, other interesting topics, such as whether multislice CT angiography would ever replace diagnostic angiography and “tomorrow’s innovations,” including a new approach for treating coronary ostial-bifurcation lesions and a novel remote control angioplasty system, also captured the audience’s attention.
Will Computed Tomography Replace the Catheter in Diagnosing CAD?
This was one of the featured discussions during PCR this year. According to Pim de Feyter, M.D., Ph.D., (Thorax Center, Rotterdam University Hospital, Rotterdam, The Netherlands) in a statement to the EuroPCR Daily, multislice computed tomography coronary angiography (or MSCT-CA) “works well to rule out patients without [CAD]” about 96 percent of the time. MSCT-CA also works to detect SVG disease in more than 90 percent of cases and graft patency 100 percent of the time.
Dr. de Feyter, who has authored several books on radiology, including books on this topic, indicates that MSCT-CA still has its limitations and comes with a steep learning curve. MSCT-CA “resembles an airplane cockpit with thousands of unknown buttons,” stated Dr. de Feyter. Nevertheless, he believes that the technology is viable and that the learning curve can be overcome if cardiologists and radiologists can work together.
The New Abbott Vascular
In an effort to phase out the Guidant brand name, Boston Scientific sold Guidant Vascular Interventions to Abbott Laboratories, which merged Guidant’s business with its own vascular device business. Nicky Spaulding, president of International Operations of the newly formed Abbott Vascular, indicated in an interview given to EuroPCR Daily that the fusion between the two business groups was complementary.
“The world of intervention has evolved and become more complex than the approaches of yesterday,” stated Spaulding.
He also believes that by fusing Guidant with Abbott, Abbott Vascular gets the best of both worlds: A top medical device company on the cutting edge of interventional medicine, coupled with the pharmaceutical capabilities of Abbott Laboratories. Spaulding foresees launching both the XIENCE V (Guidant) and ZoMaxx (Abbott) DES systems in the coming year in Europe.
“We believe [both DES systems] offer second-generation technologies over and above what is available today,” he said.
According to Spaulding, great things can be expected from the new Abbott Vascular in the coming year, such as new clinical data on their two DES platforms, as well as discussion on future generation DES technologies (e.g., bioabsorbable stents). The new company also plans to tackle vulnerable plaque and to introduce concepts for new therapies and technologies.
Stents, Stents and More Stents!
DES were definitely the focal point of this meeting, which hosted discussions ranging from when to use DES to novel coronary stent technologies. Outside the U.S. there are many more coronary stent options from which to choose. Doctors and hospitals can select from a wide range of paclitaxel to rapamycine and tacrolimus coated stents to varying stent designs and materials. Bare-metal stents in most cases are used as frequently as DES in many European countries.
Because stent choice is much greater, the competition is fiercer. There were at least 27 companies showcasing their stent technologies — too many to discuss in detail. However, below is a description of some of the novel stent technologies available to hospitals and physicians abroad.
Novel Stenting Concepts
Aachen Resonance (Aachen, Germany) has developed several active and passive coated stent technologies. The company’s ARtax, a paclitaxel eluting stent, has a dual-drug release feature. The drug (paclitaxel) is layered on top of the polymer, which allows the drug to be released quickly. A second layer incorporates the drug into the polymer for slower release. The top outer layer allows 80 percent of the drug to be released within five days of deployment, while the polymer-drug layer (or second layer) elutes more slowly over time. This structural coating allows for continuous drug delivery that helps inhibit cell functions that cause restenosis and smooth muscle cell proliferation.
Aachen has also developed a stent that combines an endothelial cell capture system and an antimitotic drug. The “DoubleFace” stent is dually coated, with the lumenal side of the stent having the endothelial cell capture coating, while the ablumenal side is coated with paclitaxel.
Both the ARtax and the DoubleFace stents use Aachen’s FlexForce stent platform as the delivery vehicle. The stent features a closed cell design and low profile stainless steel. The FlexForce’s main attributes include low recoil, superior flexibility and high radial strength.
Matching Stents to Vessels
The Skylor cobalt-chromium stent (Invatec, Roncadelle, Italy) is unique in design. Invatec has developed Diameter Specific Design, a stent technology based on vessel size. For example, a small vessel stent is constructed of three circumferential cells, whereas the large vessel stent has five circumferential cells. The small vessel stent has a strut thickness of 70 µm, while the medium vessel stent has a strut thickness of 80 µm and the large vessel stent is 95 µm. The stent is available with rapid exchange technology and is 0.014-inch guide wire and 5F guiding catheter compatible. Invatec’s Skylor Co-Cr Stents boast superior flexibility, well-balanced scaffolding and low crossing profiles.
The Other Rapamycine Stent
MicroPort Medical’s (Shanghai, China) FIREBIRD rapamycine eluting stent technology is delivered on MicroPort’s MUSTANG stent delivery system. The system delivers stents to complex lesions and offers accurate stent placement. The FIREBIRD is a rapamycine-eluting MUSTANG stainless steel stent.
The stent features a strut thickness of 0.0034 inches and is compatible with 5F guiding catheters. The MUSTANG’s small and large sinusoidal stent design provides balance between strength and flexibility. It features excellent vessel conformity and its cell design provides side branch access without compromising wall coverage. The FIREBIRD boasts a three level coating process:
• Level 1 is the polymer base coating. The polymer ensures adhesion of both the polymer to the stent and the drug to the polymer. This is an important feature, particularly during stent delivery and dilatation.
• Level 2 is the drug layer. The second layer is a combination of the rapamycine and polymer.
• Level 3 is the “top coating.” This last layer ensures that the drug is evenly released into the vessel wall.
From Passively Coated to Drug-Eluting Stents — The Choice is Yours
The Sorin Group (Saluggia, Italy) showcased two interesting stent technologies: The JANUS Flex tacrolimus-eluting Carbostent and the Tecnic Carbostent Plus.
A stainless steel stent with a turbostatic carbon coating (Carbofilm), the JANUS Flex tacrolimus-eluting stent features a unique polymer-free drug delivery platform. The JANUS is a slotted tube multicell design and is MRI safe with a stent strut thickness of 0.11 mm.
The JANUS’ design also incorporates micro trenches from which the drug is eluted, alleviating the need for a polymer carrier. Unlike conventional DES technologies — such as Taxus and Cypher that are circumferentially coated, which can leach drug into the bloodstream over time and delay vessel healing due to their nonerodable polymers — the JANUS’ unique micro trenches provide targeted drug delivery. This allows the drug to be directionally delivered into the vessel wall, ensuring only drug gets delivered into the vessel wall.
Sorin’s Tecnic Carbostent Plus is a nondrug-eluting Carbofilm coronary stent. The Tecnic boasts some very unique features, starting with the stent’s dedicated cellular design.
“Each cell is an elemental structure that realizes a full, self-contained mechanical functionality in order to optimize individual response to expansion, flexure and torsion,” states the company’s Web site. Furthermore, the Tecnic’s optimized cell-to-size ratio provides stents tailored to small, medium or large sized vessels. The Carbostent coating eliminates metal leaching that may cause a thrombogenetic response and minimizes interference with endothelialization. The stent has two platinum radiopaque markers on board that facilitates visualizing the stent pre- and post-deployment.
Head-to-Head DES Trial Updates
Some newly and recently published head-to-head DES trial updates were presented at EuroPCR 2006.
Results from the 1300-plus patient REALITY trial (published in the Journal of the American Medical Association [JAMA] in 2006), as well as results from the ISAR-DIABETES trial (published in the New England Journal of Medicine in 2005) and ISAR-SMART 3 trial (published in the European Heart Journal in 2006) were presented. The results from these three studies demonstrated Cypher’s (Cordis, Miami Lakes, FL) overall superiority over Taxus (BSC, Natick, MA) in terms of late loss and, in most cases, restenosis, as well as for fewer target vessel revascularizations (TLR).
Results from the ISAR TEST trial, a study to assess whether a polymer-free, rapamycine-eluting stent was inferior to Taxus, were also presented. The results from this study concluded that a polymer-free rapamycine-eluting was not inferior to Taxus in terms of restenosis, late loss, combined death and MI and TLR.
Brief summaries for each study mentioned above, as well as tabulated results from each study are presented below.
REALITY
Eight-month binary restenosis data and 12-month event rate data was presented from the REALITY trial, which compared the safety and efficacy of Cypher and Taxus (see Table 1) in over 1,300 patients that were randomized either to Cypher or Taxus stents. The primary endpoint was in-lesion, binary restenosis at eight months with angiographic follow-up.
Overall, Cypher performed slightly better than Taxus, even though the results were not “statistically significant.” One result that is worth mentioning is the stent thrombosis rate in the Cypher arm. Cypher was less thrombogenic than Taxus by more than 1.2 percent (0.7 percent vs. 1.9 percent; P-value of 0.06).
ISAR-DIABETES
ISAR-DIABETES was a study undertaken to demonstrate that Taxus was not inferior to Cypher in preventing restenosis in diabetic patients. Both insulin dependent and noninsulin dependent diabetics were included in this single-center, randomized trial. Two hundred fifty patients were enrolled in the study. The primary endpoint for ISAR-DIABETES was in-segment late lumen loss with angiographic follow-up from six to eight months. Results are presented in Table 2.
In terms of late loss and restenosis, Cypher was found to be superior to Taxus. Although not found to be statistically significant, nearly half as many diabetic patients randomized to Cypher required repeat revascularization. Fewer patients died in the Cypher group, but more patients suffered MIs in the Cypher group than in the Taxus group.
ISAR-SMART 3
The ISAR-SMART 3 study was undertaken to see which stent (Cypher or Taxus) performed better in small vessels (see Table 3 for results). Three hundred eighty patients at two centers were randomized to receive either a Cypher or Taxus stent. Patients with vessels less than 2.8 mm in diameter were included. Patients with diabetes, recent MI and stenosis of the left main coronary artery were not enrolled.
The primary endpoint for this study was late loss as assessed by angiographic follow-up from six to eight months. One hundred fifty-nine patients were available for follow-up in the Cypher group, compared to the 154 in the Taxus group.
In small vessels, Taxus was superior to Cypher in terms of restenosis. However, more patients required revascularization of the target lesion in the Taxus arm than those in the Cypher arm.
ISAR TEST
The objective of the ISAR TEST trial was to assess whether a polymer-free, rapamycine-eluting stent was inferior to a Taxus stent. Four hundred fifty patients at two centers were randomized to receive either the nonpolymer rapamycine stent or a Taxus stent. Primary endpoint for this study was in-stent late loss. Binary restenosis was also assessed by angiography from six to eight months. Death, MI and TLR were measured at nine months. Results are presented in Table 4.
The nonpolymer coated rapamycine
-eluting stent fared no worse than the Taxus stent. These results provide new insight into whether a polymer is needed to carry and deliver a drug into the vessel wall. No polymer on a stent means that once the drug is eluted, all that is left is a bare metal stent. Studies have shown that vessels endothelialize better with bare metal stents. If the goal of DES is to decrease restenosis that reduces the need for subsequent revascularizations, then nonpolymer coated drug-eluting stents might be the solution. This issue was discussed during a featured session regarding the precautionary use of DES at EuroPCR.
The Debate Rages On:
Precautionary Attitude Toward Full DES Adoption
Parts of Europe have adopted a precautionary attitude toward full-out use of DES. According to industry data and depending on the country, DES adoption and usage in Europe ranges anywhere between 55 to 75 percent. This explains why so many stent manufacturers offer alternative coronary stent technologies to DES as part of their product portfolios.
One possible reason for this attitude is the fact that many experts and physicians alike are not convinced that DES are appropriate for all. In a statement to the EuroPCR Daily, professor Jean Marco (Pasteur Clinic, Toulouse, France) stated that “based on the evidence that we have today, the only promise of DES is the reduction of clinically driven [TLR] without reduction of cardiac mortality or MI.”
After reviewing the two- and three-year follow-up data from the RAVEL and SIRIUS trials, Marco’s statement seems accurate. Nine-month MACE rates from the SIRIUS trial were 7.1 percent and 18.9 percent respectively for Cypher and BxVelocity. Two-year follow-up MACE rates increased roughly three percent for Cypher and approximately six percent for BxVelocity to 10.1 percent and 24.4 percent respectively.
One-year combined MACE rates in the RAVEL trial were 5.8 percent for Cypher and 28.8 percent for BxVelocity. Three-year combined MACE rates in the RAVEL trial practically tripled to 16.7 percent in the Cypher group and increased by approximately six percent in the BxVelocity group.
Late thrombosis as a result of discontinuing dual anti-platelet therapy and issues of hypersensitivity to nonbiodegradable polymers have been linked to delayed vessel healing (or endothelialization) and increased incidences of MI.
Looking Toward Tomorrow
There was plenty to see in the Innovative and Emerging Technology section at EuroPCR 2006, from a novel bifurcation stenting technology and bioengineered covered stents to a remote controlled angioplasty system for interventional cardiologists to protect themselves from hazards associated with exposure to harmful radiation.
Cappella is Heard Loud and Clear
Cappella Inc. (see related story in the May/June issue of Diagnostic & Invasive Cardiology) has developed a unique approach and device to treat ostial-bifurcation lesions. Professor Campbell Rogers (Harvard University, Boston, MA), one of the Sideguard principal investigators, presented animal data on Cappella’s Sideguard Ostium Protection Device (OPD) during an interactive session for Innovative and Emerging Technologies.
Cappella is exploring the use of biodegradable polymer carriers for its DES system.
Remote Control
Angioplasty — Can It Be True?
Remote control cars and planes are pretty common, but what about remote controlled angioplasty? The future is here and Corindus Inc. (Auburndale, MA) is bringing it. Corindus’ CorPath system allows physicians to perform angioplasties from a remote location in the cath lab without exposing themselves to harmful radiation. Because CorPath is compatible with most cath lab imaging technologies, it has caught the attention of some of the larger players in this industry, stated Corindus CEO Tal Wenderow.
The CorPath can remotely maneuver guide wires and catheters through arteries using the Physician Workstation’s joystick and touchscreen panel.
Au Revoir Paris, Bienvenido a Barcelona
Next year EuroPCR 2007 moves to Barcelona, Spain. In the meantime, the U.S. will host TCT 2006 Oct. 22-27 and ACC 2007 March 24-27. This year’s EuroPCR may well be a preview of what’s to come at the American meetings. Keep an eye on Abbott Vascular, particularly at TCT 2006, where the company will probably have some updated data to present about its XIENCE V and ZoMaxx DES systems.
