News from the Transcatheter Cardiovascular Therapeutics Meeting (TCT): Part I

Boston Scientific Announces Two-Year Follow-Up Data from the TAXUS II Clinical Trial Boston Scientific Corporation announced two-year follow-up data from its TAXUS II paclitaxel-eluting stent system clinical trial. The results provided two-year clinical outcomes, as well as the largest, long-term prospective quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) follow-up data of any drug-eluting stent trial to date. The data demonstrated that the safety and efficacy benefits associated with the Taxus stent system were maintained at two years. The company made the announcement at the annual Transcatheter Cardiovascular Therapeutics symposium in Washington, D.C. The two-year data from TAXUS II clearly demonstrate the sustained safety and effectiveness of the Taxus paclitaxel-eluting stent system in the treatment of de novo coronary artery disease, said Professor Antonio Colombo, MD, Columbus Hospital and San Rafaelle Hospital in Milan, the trial’s Principal Investigator. This data indicates that Taxus stents may prevent rather than merely delay in-stent restenosis. The large patient cohorts and long-term angiographic and IVUS data provide an especially rich source of information on the excellent performance of the Taxus system. The study’s results indicate a continued significant difference for both the slow- and moderate-release formulation cohorts in target lesion revascularization (retreatment rate, or TLR) as compared to the combined control group. The study reported a TLR rate of 5.5 percent (7/127) for the slow-release formulation cohort and 3.9 percent (5/127) for the moderate-release formulation cohort, as compared with 15.5 percent (41/264) for the combined control group. This included eight new TLR events (percutaneous coronary intervention, or PCI) between one and two years in the combined control group compared to one new event in the slow-release formulation group and no new events in the moderate-release formulation group. The TAXUS II two-year follow-up included the largest prospective angiographic and IVUS two-year sub-study population (210 patients) in interventional cardiology. Angiographic data demonstrated stable late loss out to two years with sustained statistical benefit over the control group. The benefit in percent net volume obstruction as the primary endpoint at six months was also maintained out to two years, as demonstrated by the IVUS sub-study data. The two-year results for TAXUS II support long-term safety, as incidences of aneurysms, incomplete apposition and stent thromboses were all low and comparable to control rates. No new aneurysms were seen at 2 years. Incidence of incomplete apposition was 8.7% for the slow-release formulation cohort and 6.5% for the moderate-release formulation cohort, versus 9.0% for the combined control group. TAXUS II is a 536-patient, 15-country, randomized, double-blind, controlled study of the safety and efficacy of a Taxus paclitaxel-eluting coronary stent, in which two sequential cohorts of patients with standard risk, de novo coronary artery lesions were treated with two different dose formulations: slow-release (SR) and moderate-release (MR). The study met its primary endpoint-six-month, percent in-stent volume obstruction as assessed by IVUS in results announced in September 2002. In March 2003, Boston Scientific announced one-year follow-up data from TAXUS II, which supported safety and efficacy. In May 2003, the Company announced additional results related to higher-risk patient subgroups, including diabetics and patients with longer lesions and smaller vessels, demonstrating that the reduction in target lesion revascularization (TLR) events for the TAXUS II subgroups at one year was equal to or better than that of the general study population. It also announced data in May 2003 demonstrating excellent performance by the Taxus stent at six months with respect to vascular healing, incomplete apposition and edge effect following detailed IVUS analysis. The Company has commercialized the slow-release formulation; the moderate-release formulation is not available for commercial distribution. At two years, patients returned for clinical follow-up and approximately 50 percent of patients were enrolled in a special angiographic and IVUS sub-study to better ascertain the longevity of the safety and efficacy outcomes seen at six months. Clinical follow-up in TAXUS II included 96 percent of the patients enrolled at two years (512/536). The follow-up rate for angiographic IVUS examinations was 231/536, resulting in different denominators for the follow-up subgroups. Boston Scientific Also Announces Two-Year Follow-Up Data from the TAXUS IV Clinical Trial Benefits maintained at two years Boston Scientific Corporation also announced two-year follow-up data from its TAXUS IV clinical trial. The benefits reported at 12 months for patients who received a paclitaxel-eluting stent compared to patients who received a bare-metal stent were maintained at two years. The company made the announcement at the annual Transcatheter Cardiovascular Therapeutics symposium in Washington, D.C. The results support safety and efficacy, as demonstrated by low rates of target lesion revascularization (retreatment rate, or TLR) that were maintained at two years. The Taxus group reported a 5.6 percent (36/645) TLR rate compared with 17.5 percent (112/640) in the control group. The follow-up rate at two years was outstanding with 97 percent of patients returning. The rate of patients living free of TLR events was 94.4 percent at two years for the Taxus group, as compared to 82.6 percent for the control group. Results for diabetic patients (including oral and insulin-requiring diabetics) in the Taxus group also showed that benefits were maintained at two years. The TLR rate for diabetics was 8.0 percent (12/150) compared to 22.0 percent (35/159) in the control group. Diabetic patients are more likely than non-diabetic patients to experience restenosis following angioplasty and stenting with bare-metal stents, and may stand to benefit substantially from drug-eluting stent technology. Diabetic patients are expected to represent approximately 40 percent of coronary interventions. Gregg W. Stone, MD, the study’s Principal Investigator and Professor of Medicine, Columbia University Medical Center in New York, said, These outcomes establish the durability of the Taxus stent in a broad range of complex patients and blockages. At two-year follow-up, the incremental benefits of having received the Taxus stent system rather than a bare-metal stent continue to increase with no evidence of late catch-up apparent. TAXUS IV is a randomized, double-blind pivotal trial designed to assess the safety and efficacy of a paclitaxel-eluting coronary stent system in reducing restenosis in de novo lesions 10-28 mm in length and 2.5-3.75 mm in diameter. The study, which enrolled 1,326 patients at 73 sites in the United States, is using Boston Scientific’s Taxus Express coronary stent system. Medtronic Announces Preliminary Data from the MAVErIC I & II Carotid Stenting Clinical Trials Stephen R. Ramee, MD, the Co-Principal Investigator of the MAVErIC(a) Clinical Trial, presented positive preliminary 30-day data from the MAVErIC II trial and one year data from the MAVErIC I trial at the Transcatheter Cardiovascular Therapeutics (TCT 2004). The MAVErIC I and II clinical studies, which comprise a total of 498 patients, are designed to evaluate the short- and long-term safety and efficacy of Medtronic’s Exponent Carotid Stent System and the GuardWire® Balloon Occlusion device in reducing the incidence of stroke and death in patients with carotid artery disease. The preliminary data from these studies suggests that the GuardWire system, when used with the Exponent carotid stent, is successful in treating high risk patients with carotid artery disease, said Dr. Ramee. This data indicates that balloon occlusion devices, such as the GuardWire system, used in this manner are similar to filter devices and can produce favorable results in carotid stenting procedures. Depending on the patient, it may be appropriate to fully seal a vessel via a balloon system to prevent stroke and this data suggests that the GuardWire system is a viable option for meeting this important objective. The MAVErIC II trial is a 399-patient pivotal trial designed to study the safety and efficacy of the Self-Expanding Exponent Carotid Stent with the GuardWire Balloon Occlusion and Aspiration System for the treatment of carotid stenosis. The preliminary 30-day results showed a Major Adverse Event (MAE) rate of 5.3 percent. MAE includes any stroke, myocardial infarction (MI) and/or death. The MAE rate for MAVErIC II included an MI rate of 2.0 percent, a death rate of 1.0 percent and stroke rate of 3.3 percent. The study also assessed lesion, device and procedural success, with both the Exponent stent and GuardWire system performing well in the study. The MAVErIC II Clinical Trial completed enrollment in August 2003 and is being performed at 34 centers in the United States. Patients in the MAVErIC II trial will be followed up to one year after their procedure. Medtronic anticipates that final patient follow up will occur in the fall of 2004. The MAVErIC II trial is led by co-principal investigators: Stephen R. Ramee, MD, FACC, Director of the Cardiac Catheterization Laboratory at the Ochsner Clinic Foundation, New Orleans, and Randall T. Higashida, MD, Clinical Professor of Radiology and Neurological Surgery at the University of California’s San Francisco Campus. The first MAVErIC II patient enrollment was initiated by James D. Joye, DO, FACC, Director of the Cardiac Catheterization Laboratory at El Camino Hospital in Mountain View, Calif. The MAVErIC I clinical trial was a 99-patient feasibility study designed to demonstrate the safety of the Self-Expanding Exponent Carotid Stent with the GuardWire Temporary Occlusion and Aspiration System for the treatment of carotid stenosis. At one year, the study found a major adverse event (MAE) rate of 5.1 percent, which was unchanged from the 30-day results. The study also demonstrated positive device, lesion and procedural success. The MAVErIC I study completed enrollment in December 2002 and was performed at 16 centers in the United States. Medtronic intends to conduct the MAVErIC III Clinical Trial in the United States, beginning in the fall of 2004, to study the safety and efficacy of the Exponent Carotid Stent System with the Interceptor® PLUS Filter System in reducing the incidence of stroke and death in patients with carotid artery disease. The Exponent stent system is an investigational device and is not available for commercial distribution in the United States. The GuardWire system, the first FDA-cleared embolic protection device, has been available for use in U.S. markets since June 2001 for treating diseased saphenous vein grafts (SVGs). (a) MAVErIC (Evaluation of the Medtronic AVE Self-Expandable Carotid Stent System with Distal Protection In the Treatment of Carotid Stenosis) CryoPlasty® Therapy Now Available for Limb Salvage CryoVascular Systems, Inc. has expanded the PolarCath CryoPlasty System to include a new line of catheters to treat atherosclerotic occlusive disease in the infrapopliteal and tibioperoneal arteries. The infrapopliteal catheters are used with CryoVascular’s PolarCath System, a peripheral CryoPlasty system that treats stenosis by dilating and cooling arteries to -10C/+14F with a balloon filled with nitrous oxide. Recently cleared by the FDA, the PolarCath Infrapopliteal Catheter is being used at approximately 100 hospitals across the country. A prospective, multi-center study (Below the Knee Chill) is also being initiated at 30 hospitals across the country, evaluating the role of the CryoPlasty technology in avoiding major amputation in patients with severe disease. Enrollment began in September 2004, and preliminary results are expected to be presented as early as January 2005 at the International Symposium on Endovascular Therapy (ISET) in Miami and the Society of Interventional Radiology (SIR) Annual Meeting in New Orleans in March. Patency at one year for conventional catheter-based interventions is estimated at 59% for PTA and 62% for stenting. The dominant contributing factors affecting the ability to keep the lower extremity arteries open over time is the length of the vessel that is affected as well as whether or not the vessels below the knee have adequate flow. The tendency to treat patients at later stages of disease progression almost always means very long lesions and little, if any, flow below the knee. Without an effective means to open these small, delicate vessels, many patients ultimately require bypass. Surgical vessel bypass has demonstrated one-year patency rates as high as 83%; however, many times, the vessel used as a bypass conduit is the same one used for coronary bypass. Since most of these patients suffer from systemic vascular disease, preserving the conduit vessels for use in the heart is critical. Additionally, many of these patients have poor overall health and are no longer suitable candidates for a surgical procedure. Since the launch of the PolarCath System in 2003, physicians using the CryoPlasty procedure as a primary therapy have observed a significant reduction in their use of stents, coinciding with a lower rate of flow-limiting dissection and vessel recoil. Clinical data indicate that 83% of artery blockages treated with the PolarCath System remained open after 9 months. During a CryoPlasty procedure, a catheter advances a balloon to the site of the occlusion and nitrous oxide, rather than saline, is used to inflate the balloon. The nitrous oxide changes into gas upon entering the balloon, cooling it to -10C/14F. The cold is believed to have several beneficial vascular effects as it opens the artery, including weakening the plaque to allow it to reshape more easily, reducing vessel elasticity to minimize reclosing of the vessel, and minimizing inflammation and scar tissue formation. Research presented at the Annual Transcatheter Cardiovascular Therapeutics Scientific Symposium showed outcomes of the first patients to receive the therapy. Ninety-five percent of the patients were able to avoid almost-certain amputation below the knee as a result of treatment with the PolarCath System Infrapopliteal Catheter. Patients with this type of advanced disease many of whom are diabetic have very few treatment options, said James Joye, DO, director of the Cardiac Catheterization Lab at El Camino Hospital, Mountain View, Calif., and co-founder of the CryoPlasty technique. The CryoPlasty procedure is a conservative no harm therapy that can be employed early in the disease process, and can be repeated if necessary without hindering future treatment options. It may be possible to delay progression of the disease to the limb-threatening stage. Outcomes of the first patients treated with CryoPlasty reported at TCT: 26 lesions in arteries below the knee were treated in 20 patients who had leg pain at rest or ischemic ulceration and gangrene. All 20 patients received the CryoPlasty technique using the PolarCath System Infrapopliteal Catheter as the primary therapy; 6 patients with severely blocked vessels underwent atherectomy to create a channel that would allow passage of the catheter. Limb salvage with freedom from major amputation was achieved in 19 patients (95 percent) and only 1 patient (5 percent) proceeded to below-the-knee amputation. Five patients (25 percent) underwent toe or transmetatarsal amputation of pre-existing gangrene and 1 patient who was treated for bilateral disease underwent subsequent bypass surgery in one limb. The PolarCath System is distributed by Boston Scientific Corporation.

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