Conor Medsystems (Menlo Park, California) presented acute and follow-up data from the PISCES (Paclitaxel In-Stent Controlled Elution Study) trial during last month's EuroPCR (previously Paris Course on Revascularization) conference in Paris. The company said results from the trial support the safety of its stents and demonstrated in one of the study arms a binary restenosis rate of 0%. "These findings provide clear indications of optimal dosing and a superior kinetic release profile for paclitaxel in reducing restenosis using the company's novel vascular drug-delivery stent platform in the treatment of native coronary artery lesions," Conor said in a statement.
The company described PISCES as "the most comprehensive pilot study conducted to date of drug dosing and kinetics with drug-eluting stents."
Patrick Serruys, MD, of Erasmus University (Rotterdam, the Netherlands) is the principal investigator for the trial, a multicenter study involving 191 patients from 10 sites in seven countries, comparing the safety and performance of paclitaxel delivered at different rates and doses using Conor Medsystems' stainless-steel MedStent.
Each patient participating in the trial received one of six different formulations of paclitaxel that varied by dose, drug release rate (fast, medium and slow) and directionality (drug release to only the arterial wall vs. release to both the wall and the lumen). Each dosing group had at least 30 patients, with an average age of 59.
At four-month follow-up, all six formulations were determined to be safe, with a subacute thrombosis rate of 0.5% and zero deaths from discharge to follow-up. Two groups with slow release (30-day) formulations had particularly good outcomes, Conor said. In the 39-patient group receiving a 10 mcg slow-release formulation delivered to the vessel wall, the in-stent binary restenosis rate was zero and the in-stent angiographic late loss was 0.38 mm, with a 7.7% volume obstruction by intravascular ultrasound (IVUS). The target lesion revascularization rate was 2.6%. In the 30-patient group receiving a 30 mcg slow release formulation delivered to the vessel wall, the in-stent binary restenosis rate was 3.7%, with in-stent angiographic late loss of 0.30 millimeters, and 5.1% volume obstruction determined by IVUS. The TLR rate was 3.3%.
The remaining four groups with faster release kinetics, ranging from five to 10 days for either 10 mcg or 30 mcg per stent, had less efficacy with respect to angiographic and IVUS endpoints. Conor said the study results "indicate that the drug release rate and direction of delivery have an effect on treatment outcomes, as well as confirm dosing regimens for the company's current clinical program."
Frank Litvack, MD, chairman and chief executive officer, said, "For the first time, we have a clear indication of the benefits of kinetic release and controlled dosing in improving patient outcomes. We are pleased with these encouraging results which address significant problematic issues in this field and which support our unique stent and polymer platforms."
Litvack said the dosing information obtained from the study "is contributing to the planning of our COSTAR and EUROSTAR studies, and the validation of the benefits of kinetic release has positive implications for the broad application of our platform for vascular drug delivery."
Conor's drug-eluting stents are the first non-surface-coated stents specifically designed with polymer reservoirs for controlled, tailored release kinetics with the use of a fully bio-erodable polymer. The company said pre-clinical studies have demonstrated that there is no residual polymer or drug after the specified release period.
"Comparatively, MedStent required approximately one-10th to one-quarter of the drug dose currently used with commercially available stents delivering paclitaxel," Conor said in a statement.
The company is engaged in several international clinical trials for each of its drug-delivery stent platforms stainless steel and cobalt chromium. In addition to the PISCES trial for the stainless-steel stent, Conor has two trials under way with its paclitaxel-eluting cobalt chromium stent COSTAR (CObalt chromium STent with Antiproliferative for Restenosis) and EUROSTAR (EUROpean cobalt chromium STent with Antiproliferative for Restenosis).
Conor said it plans to seek regulatory approval for its proprietary cobalt chromium stent worldwide. In addition to the initial focus on the treatment of restenosis and vascular disease, the company also is exploring additional indications where controlled drug release from a medical device is expected to provide therapeutic advantage.
Abbott sees 'new era' in vascular closure
Abbott Vascular Devices (Redwood City, California), a division of Abbott Laboratories (Abbott Park, Illinois), unveiled the StarClose Vascular Closure System. The company said the introduction marks the world's first circumferential clip-based vascular closure device, and ushers in "a new era in vascular access closure devices."
StarClose features a Nitinol clip designed to promote the primary healing process to achieve a secure close of femoral artery access sites following diagnostic or interventional vascular procedures. The clip provides 360-degree tissue apposition for rapid healing and immediate hemostasis, Abbott said. StarClose received CE mark certification in February and is available for sale in the European Economic Community.
Robert Hance, president of Abbott Vascular Devices, said the introduction of StarClose solidifies his company as "an innovative leader in vessel closure." StarClose joins a product line that includes the Perclose suture-mediated closure family and Chito-Seal topical hemostasis, giving physicians a patient-centric approach when addressing a broad spectrum of clinical needs.
Hance said the device requires only four clicks to achieve a secure, extravascular close, meaning that nothing is left inside the artery itself. The clip closes the closure site entirely from the outside of the vessel. Abbott said physician feedback regarding ease of use and the time it takes to close the vessel has been "positive." In addition, it said, "the intuitive design of StarClose shortens the learning curve for physicians."
Peter Ruygrok, MD, principal investigator for the StarClose New Zealand study, consultant cardiologist at Auckland City Hospital and clinical associate professor at the University of Auckland (Auckland, New Zealand), said, "StarClose heralds in a new generation of rapid, simple arterial puncture site closure devices that are shown to be safe even in patients receiving strong blood thinners such as GPIIb/IIIa inhibitors. I have no doubt it will modernize the management of puncture sites following catheterization and percutaneous intervention."
An additional feature of the StarClose system allows physicians to close the artery through the introducer sheath. Abbott said this through-the-sheath (TTS) approach expedites patient management, as extra guide wire insertion and sheath exchange steps are removed from the procedure. Moreover, it said, "TTS allows the interventionalist to use the very same pathway established during the catheterization procedure to deliver the StarClose clip directly to the puncture site, thereby shortening the procedure for the interventionalist."
Tony Chou, MD, general manager of vessel closure technologies at Abbott Vascular Devices, said, "The StarClose system provides an original approach to managing vascular access sites . . . [incorporating] a high degree of confidence in gaining hemostasis, a rapid means of deployment, and [giving] physicians a true through-the-sheath approach."
Abbott Vascular Devices launched the CLIP (Clip cLosure In Percutaneous procedures) study a U.S.-based clinical trial of StarClose for extravascular closure in diagnostic and interventional cases in March, with StarClose patients randomized against manual compression. The first Perclose system was launched in 1994, enabling physicians to use suture-mediated closure technology to more quickly close accessed vessels in cardiac catheterization procedures. Such improved closure allows patients to ambulate safely, improves patient comfort and allows patients to go home sooner.
Abbott Laboratories acquired Perclose in 1999.
Study backs Cypher's value for diabetics
Data presented at the EuroPCR meeting provided further clinical evidence that use of the Cypher sirolimus-eluting coronary stent, made by the Cordis (Miami Lakes, Florida) unit of Johnson & Johnson (New Brunswick, New Jersey), is an effective treatment for a broad range of patients including diabetics, who are some of the most difficult-to-treat patients.
The six-month data from the e-Cypher Registry, which Cordis terms "the world's largest Internet-based, post-market surveillance study," highlights key areas of improvement, including a large number of diabetic patients that did not have to be retreated for coronary blockages, according to the company. The diabetic patient subset is the single largest high-risk group of patients enrolled in this study. While still enrolling, the registry currently is comprised of 12,180 patients who received the Cypher Stent in 275 medical centers outside of the U.S. Physicians conducted clinical follow-up and adjudication on more than 80% of the patient population in the study, providing further validity of the data.
"The results are encouraging and provide a much needed broader view of the efficacy of the Cypher Stent in a range of lesion subsets and high-risk patient populations," said Philip Urban, MD, director of invasive cardiology at La Tour Hospital (Geneva, Switzerland). In the overall population, Urban reported a 2.5% major cardiac adverse event (MACE) rate, 1% target lesion revascularization (TLR) rate that included angioplasty and by-pass surgery and a 0.3% sub-acute thrombosis (SAT) rate.
Diabetic patients, especially insulin-dependent diabetics, are considered one of the highest-risk patient subsets to treat for cardiovascular disease, generally having a more diffuse and aggressive vascular disease than non-diabetic patients. Nearly 30% of the patients enrolled in the e-Cypher Registry are diabetic, of whom more than one-third are insulin-dependent. Urban highlighted the excellent results achieved in the overall diabetic subset in whom the six month MACE rate is 4.2%, TLR rate is 1.4%, and the SAT (clotting) rate is 0.5%.
The results of the insulin-dependent diabetic patient population were similar to those of the overall diabetic patient population, with a six-month MACE rate of 5.9%, TLR of 1.5% and SAT rate of 0.4%. "These results are particularly impressive given the significant difference in the pre-existing medical history of diabetic patients vs. the non-diabetic population," said Urban.
A total of 14,300 patients from 275 sites in Latin America, Europe, Middle East and Asia Pacific, out of the target patient population of 15,000, have been enrolled in the e-CYPHER database. Of these, 83% have completed 6-month follow-up. The registry is monitored by an independent advisory board with adverse events/endpoints adjudicated by an independent endpoints review committee.
In other EuroPCR news:
Mentice (Gothenburg, Sweden/San Diego, California), together with Guidant (Indianapolis, Indiana), reported that for the first time during a live-case transmission at EuroPCR, a carotid stenting procedure was rehearsed on a virtual reality simulator before the procedure was performed on the patient. The training simulator uses technology developed by Mentice to provide visual and tactile feedback, with the virtual anatomy used in the rehearsal created from a 3-D scan.
Jonas Ohlsson, president of Mentice, said, "In several clinical studies it has been proven that our Procedicus simulators, such as MIST and VIST, improved performance in the operating room. With the unique procedure rehearsal capability and fidelity, demonstrated at the Euro-PCR, we can now advance the field of endovascular simulation to the next-generation: patient-specific training and pre-procedure planning and rehearsal."
Radiologist Lukas van Dijk, MD, and vascular surgeon Johanna Hendriks, MD, at the Erasmus Medical Center (Rotterdam, the Netherlands) performed both the virtual and actual procedures. Vascular surgeon Marc van Sambeek, MD, at the same hospital, moderated the focus session.
Guidant reported CE mark approval and launch of the Multi-Link Mini Vision Coronary Stent System, the company's first cobalt chromium stent for treating coronary artery disease in small vessels, and CE mark approval and launch of the next-generation Voyager Coronary Dilatation Catheter. Dana Mead Jr., president of Guidant's Vascular Intervention unit, said that both devices "will enable physicians to more easily treat patients with complex coronary artery disease . . . we believe that this new stent system will build upon our market-leading position in the European metallic stent market."
Cobalt chromium technology is designed for small-vessel stenting by allowing stents to have a thinner strut stent design and improved deliverability. With the introduction of the Multi-Link Mini Vision Coronary Stent System, cobalt chromium stents are now available in Europe, the Middle East, Australia and New Zealand.
Guidant said it expects to launch the Multi-Link Mini Vision Coronary Stent System in the U.S. market and other geographies later this year. The Voyager RX Coronary Dilatation Catheter was launched immediately in Europe, and the devices were to be introduced in Asia, the Middle East and Latin American countries shortly thereafter.