News from the 22nd Annual Transcatheter Cardiovascular Therapeutics (TCT) Scientific Symposium

EVEREST II Data Show Clinical Benefit From Mitral Valve Clip Device

A percutaneous mitral valve clip designed to stop mitral valve regurgitation demonstrated clinical benefit as measured by the degree of mitral regurgitation, according to a study presented at TCT. Mitral valve regurgitation is one of the most common forms of heart disease. The study was led by James Hermiller, MD, Director of Cardiovascular Intervention at the St. Vincent Heart Center of Indiana (Indianapolis, IN). “Significant measures of clinical benefit are observed one year following successful therapy,” said Dr. Hermiller. The study, EVEREST II, is a prospective, multi-center, randomized controlled trial designed to compare the safety and effectiveness of the MitraClip System (Abbott Vascular, Redwood City, CA) with mitral valve surgery in the treatment of mitral regurgitation (MR). Measures of 12-month clinical benefit, defined as improvements in left ventricular (LV) function and symptomatic improvement, were evaluated for the Device Group and Control Group, and have been previously reported. However, observed clinical benefit by 12-month MR grade has not been reported. Significant improvement in LV function, NYHA Functional Class, and Quality of Life scores was observed for all device patients with ongoing success (MR less than or equal to 2+ at 12 months). Patients with MR reduced to 1+, 1+ to 2+, or 2+ at 12 months demonstrated marked clinical benefit, with significant improvements noted from baseline to 12 months. ————————————————————

First-In-Human Study of Robotically-Assisted PCI System Demonstrates Safety, Feasibility

The first-in-human study of a robotically-assisted percutaneous coronary intervention (PCI) system, the CorPath 200 System (Corindus Vascular Robotics, Natick, MA), presented at TCT, demonstrated that the technique was safe and feasible. The current practice of PCI still presents multiple limitations and potential hazards for both the patient (radiation exposure, contrast media use) and the operator (spine strain, accumulated radiation). According to the study, robotically-assisted PCI demonstrates the potential to decrease radiation exposure, contrast media usage, and improve technical precision. The study was led by Juan F. Granada, MD, Executive Director and Chief Scientific Officer of The Jack H. Skirball Center for Cardiovascular Research at the Cardiovascular Research Foundation and Giora Weisz, MD, Director of Clinical Cardiovascular Research at the Center for Interventional Vascular Therapy (CIVT) at New York-Presbyterian Hospital/Columbia University Medical Center. “Use of robotics is a very exciting development in interventional cardiology,” said Dr. Granada. “The operator is able to perform the procedure from a remote, radiation-protected control console. Initial experience with the use of this system demonstrated procedural effectiveness that was comparable to manual PCI.” In the study, a total of eight patients were enrolled in a single-arm, open-label, prospective study performed at the Corbic Research Institute (Corbic Institute, Envigado, Colombia). All patients had evidence of myocardial ischemia, documented de novo coronary stenosis, and clinical indication for PCI. Using a remote system that is compatible and capable of advancing, retracting, and rotating 0.014” guidewires and rapid exchange catheter systems, the operator manipulates the interventional devices from a control console with joysticks while sitting comfortably at the radiation-shielded interventional cockpit. The primary endpoint was technical success (————————————————————

Xience V Stent Shows Continued Strong Performance in Key Safety and Efficacy Measures at Two Years in Investigator-Initiated COMPARE Trial

Data presented from the investigator-initiated COMPARE trial of 1,800 real-world patients involving Abbott’s Xience V^® Everolimus Eluting Coronary Stent System and the Boston Scientific Taxus^® Liberte^® Paclitaxel-Eluting Coronary Stent System. The results from COMPARE at two years were presented by Peter Smits, MD, of Maasstad Ziekenhuis, Rotterdam, the Netherlands, during TCT. For the endpoint of major adverse cardiac events (MACE) at two years, which is a composite of all death, non-fatal heart attack (myocardial infarction or MI) and target vessel revascularization (TVR), Xience V showed a 34% lower incidence of MACE compared to Taxus (9.0% for Xience V vs. 13.7% for Taxus, p=0.0016). The composite secondary endpoint of cardiac death, non-fatal MI and target lesion revascularization (TLR) resulted in a 35% lower incidence for Xience V compared to Taxus (7.4% for Xience V vs. 11.4% for TAXUS, p=0.0038). In addition, Xience V demonstrated a 77% lower rate of stent thrombosis, defined as definite or probable according to ARC (0.9% for Xience V vs. 3.9% for Taxus, p≤0.0001); a 60% lower rate of TVR (3.1% for Xience V vs. 7.7% for Taxus, p≤0.0001); a 56% lower rate of TLR (2.6% Xience V vs. 5.9% Taxus, p=0.0005); and a 49% lower rate of non-fatal MI (3.9% Xience V for vs. 7.6% for TAXUS, p=0.0009). The stent thrombosis rate for Xience V between one and two years increased from 0.7% at one year to 0.9% at two years, while the Taxus arm increased from 2.6% at one year to 3.9% at two years. At two years, 88.6% of Xience V patients and 84.8% of Taxus patients had discontinued dual-antiplatelet therapy. The COMPARE study is a physician-initiated “all-comers” trial sponsored by Maasstad Ziekenhuis of Rotterdam, the Netherlands. The study, designed to reflect real-world, everyday clinical practice, enrolled 1,800 patients in a single-center, prospective randomized (1:1) comparison of safety and efficacy of the Xience V stent to the Taxus Liberte stent. The COMPARE trial was supported in part by an Abbott grant. All aspects of the trial were designed and conducted independent of Abbott. ————————————————————

PARTNER Trial Establishes Catheter-Based Aortic Valve Replacement as New Standard of Care for Patients Who Cannot Undergo Surgery

One-year data from the PARTNER clinical trial, published in the New England Journal of Medicine, demonstrate that transcatheter aortic-valve implantation, compared with standard therapy, resulted in significantly lower rates of death among patients who cannot undergo surgery for aortic stenosis. The results were presented at TCT. Transcatheter aortic-valve implantation (TAVI) is a new procedure in which a bioprosthetic valve is inserted through a catheter and implanted within the diseased native aortic valve. The Placement of AoRtic TraNscathetER valves (PARTNER) trial is a multicenter, randomized clinical trial comparing TAVI with standard therapy in high-risk patients with severe aortic stenosis. The co-principal investigators are Martin B. Leon, MD, and Craig R. Smith, MD, at NewYork-Presbyterian Hospital/Columbia University Medical Center. The data reflect a prespecified cohort of patients who were considered to be unsuitable candidates for surgery. The primary endpoint was the rate of death from any cause over the duration of the study. A total of 358 patients with aortic stenosis who were considered to be unsuitable candidates for surgery underwent randomization at 21 centers, including 17 in the United States. Patients randomized for standard therapy received a combination of watchful waiting, medications, and balloon aortic valvuloplasty, which can provide transient clinical benefit, but does not alter long-term outcomes. At one year, patients who underwent TAVI showed a 45% reduction in the rate of death from any cause compared with patients who received standard therapy (30.7% vs. 50.7%) and a 54% reduction in the combined endpoint of death from any cause or repeat hospitalization (42.5% with TAVI vs. 71.6% with standard therapy). Among survivors at one year, the rate of cardiac symptoms was significantly lower among patients who had undergone TAVI, as compared with those who had received standard therapy (25.2% vs. 58.0%). “Based on the reduction in mortality during the first year of the study, balloon-expandable TAVI should be the new standard of care in patients who are not suitable candidates for surgery,” said Martin B. Leon, MD, professor of medicine and director of the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital and Columbia University Medical Center. Dr. Leon is the co-principal investigator of the study. At 30 days, TAVI, as compared with standard therapy, was associated with a higher incidence of major strokes (5.0% vs. 1.1%) and major vascular complications (16.2% vs. 1.1%). In the year after TAVI, patients had no deterioration in the functioning of the bioprosthetic valve, as assessed by evidence of stenosis or regurgitation on an echocardiogram. “This study shows that transcatheter valve replacement is a safe and effective option for this life-threatening illness in patients unsuitable for surgical valve replacement,” said Dr. Smith, study co-principal investigator and surgeon-in-chief at New York-Presbyterian Hospital/Columbia University Medical Center. “Additional studies are needed to examine the increased incidence of stroke following TAVI.” According to the study authors, research is already underway on the next generation of TAVI devices that researchers hope will address the vascular complications encountered in the trial. Aortic stenosis results in a poor quality of life and a high rate of death, approximately 50 percent, in the first two to three years after diagnosis without surgical intervention. Approximately 300,000 Americans suffer from severe aortic stenosis. In clinical practice, at least 30% of patients with severe symptomatic aortic stenosis do not undergo surgery for replacement of the aortic valve because of advanced age, left ventricular dysfunction, or the presence of multiple coexisting conditions. The replacement valve used in the PARTNER trial is made of pericardial tissue leaflets hand-sewn onto a metal frame and implanted via a catheter into the left ventricle. It is then positioned inside the patient’s existing valve using a balloon to deploy the frame, which holds the valve replacement in place. The procedure is performed on a beating heart, without the need for cardiopulmonary bypass and its associated risks. The transcatheter valve procedure takes about 90 minutes, compared with four to six hours for open-heart surgery. In open-heart surgery, the surgeon cuts through the breastbone, stops the heart, removes the valve, and replaces it. Open-heart surgery can require a two- to three-month recovery period, compared with only a few days for the transcatheter approach. The multi-center PARTNER trial, which has more than 1,000 patients, began in 2007 and will be completed in 2014. The results reported at TCT reflect only the cohort of patients who are not considered candidates for surgery. The other arm of the trial, which compares transcatheter valves with surgically implanted valves, is ongoing. The executive committee of the trial includes two academic co-principal investigators, three interventional cardiologists, and three cardiac surgeons. ————————————————————

SCAI Statement on the PARTNER Trial Results

New data published in The New England Journal of Medicine show encouraging results for minimally invasive transcatheter aortic-valve implantation (TAVI) in patients with severe aortic stenosis who are too high risk to undergo surgery. While TAVI is approved for treatment of aortic stenosis in other countries, it is currently experimental in the U.S. These results are preliminary and more research is needed, but they are undoubtedly important in laying the groundwork for providing new and effective minimally invasive treatments to patients with severe disease. Aortic valve stenosis, a common heart problem in older adults, can cause shortness of breath, chest discomfort with exercise or fainting spells. Aortic stenosis worsens over time and requires open-heart surgery to replace the diseased heart valve. The rate of aortic valve replacement increases as patients get older. Unfortunately, the risk for open heart surgery generally increases for older patients. Left untreated, the disease can quickly result in death. The Placement of Aortic Transcatheter Valves (PARTNER) trial, a multi-center, randomized clinical trial comparing TAVI with standard therapy (typically balloon aortic valvuloplasty) in high-risk patients with severe aortic stenosis, showed:

• TAVI was superior to standard therapy, markedly reducing death after one year (the primary endpoint of the study). • TAVI significantly reduced the rates of death from cardiovascular causes and repeat hospitalization. • TAVI was associated with a significant reduction in symptoms, but was also associated with more neurological events (including strokes), major vascular complications, and major bleeding events as compared to the standard therapy group.

“Without exciting, new minimally invasive treatment options like TAVI, people with severe aortic stenosis will continue to have few to no treatment options and will die from their disease,” said Christopher White, MD, FSCAI, chairman, department of cardiology, and director of the Ochsner Heart & Vascular Institute, Ochsner Medical Center in New Orleans, and president-elect of the Society for Cardiovascular Angiography and Interventions. “These results are very encouraging and suggest TAVI is an effective treatment option for severe aortic stenosis in patients who cannot have surgery.” ————————————————————

Abiomed Reports Updated USpella Registry Data

Abiomed Inc. announced updated clinical data from USpella, a U.S. multi-center, observational registry of Impella 2.5^® patients. The new updates, presented at TCT 2010, reported that 24 U.S. and Canadian centers have contributed data for a total of 352 patients. The USpella registry results were last announced on May 15, 2010 at EuroPCR 2010. The updated USpella results were presented by William O’Neill, MD, University of Miami Miller School of Medicine, and Brijeshwar Maini, MD, Pinnacle Health and Vascular Institute. The updated USpella registry^* reported the following: After prophylactic Impella supported revascularization:

• Significant (17%) improvement of left ventricular ejection fraction (LVEF) • Significant improvement (49% of patients) in New York Heart Association (NYHA) class with 61% reduction in NYHA class four • Significant (25%) reduction in implantable cardiac defibrillator (ICD) target population, leading to potential cost savings • More than half of the patients (54%) were turned down for coronary artery bypass graft surgery (CABG), 59% of the patients had experienced a prior myocardial infarction (MI) • Low mortality (3.9%) and major adverse cardiac events (MACE) event rate (8.2%) in patients, compared to high-risk PCI literature^**

After emergent Impella support:

• Hemodynamic support with the Impella 2.5 (cardiac index, cardiac power output, wedge pressure, mean arterial pressure) significantly increased over the intra-aortic balloon pump (IABP) in this study • Impella improves cardiac power output (CPO), the strongest correlate of in-hospital mortality (CPO increased from 0.5 +0.2 before Impella support to 1.0 + 0.2 after Impella support) • Significant (19%) improvement of LVEF at discharge • Significant reduction (59%) in mortality in the group that received Impella before PCI • Ninety percent of the survivors recovered native cardiac function and were discharged with their own hearts

^*Significant = statistically significant with p**Syed Al, et al. Cardiovasc Revasc Med 2010; 1191–1197. ————————————————————

Fully Bioresorbable Vascular Scaffold Technology Shows Positive Data at Six and Nine Months

Abbott announced positive nine-month results from the first 45 patients enrolled in the second stage of the ABSORB trial. At nine months, Abbott’s bioresorbable vascular scaffold (BVS) demonstrated strong results that remained consistent with the six-month data from the same 45-patient group, with the rate of major adverse cardiac events (MACE) unchanged at 4.4 percent and no reports of blood clots (thromboses). These results were presented during the TCT. “I am impressed with how consistent the BVS data have been to date, as the nine-month data are compelling and supportive of earlier positive results,” said John Ormiston, MD, medical director at Mercy Hospital in Auckland, New Zealand, and co-principal investigator for the ABSORB trial. “In addition to the positive safety data we’ve seen to date, the late loss rate of 0.19 millimeters reported at six months is comparable to a metallic drug-eluting stent, and may address a limitation of metal stents by not leaving metal in the artery.” Abbott also presented six-month results for all 101 patients enrolled in the second stage of the ABSORB trial. In this complete patient population, the MACE rate remained consistent, with a nominal increase from 4.4% at six months in the first 45 patients to 5.0% at six months in all 101 patients. There were no reports of blood clots in any of the 101 patients. Patrick W. Serruys, MD, PhD, professor of interventional cardiology at the Thoraxcentre, Erasmus University Hospital, Rotterdam, the Netherlands, and principal investigator for the ABSORB trial, said, “The findings to date show that the device appears to effectively treat coronary artery disease with the possibility of restoring natural vessel function in a way that is not possible with permanent implants.” Abbott’s BVS is under investigation in two clinical studies, ABSORB and ABSORB EXTEND, and is currently not available for sale anywhere in the world. The BVS is made of polylactide, a proven biocompatible material that is commonly used in medical implants such as resorbable sutures. The ABSORB trial is a prospective, non-randomized (open label), two-phase study that enrolled 131 patients from Australia, Belgium, Denmark, France, the Netherlands, New Zealand, Poland and Switzerland. Key endpoints of the study include assessments of safety — MACE and treated-site thrombosis rates — at 30 days; six, nine, 12 and 24 months; with additional annual clinical follow up for up to five years, as well as an assessment of the acute performance of the bioresorbable vascular scaffold, including successful deployment of the system. Other key endpoints of the study include imaging assessments by angiography, intravascular ultrasound (IVUS), optical coherence tomography (OCT), and other state-of-the-art invasive and non-invasive imaging modalities at six, 12, 18, 24 and 36 months. The ABSORB EXTEND trial is a single-arm study that is currently enrolling patients at up to 100 centers in Europe, Asia Pacific, Canada and Latin America. The trial will enroll approximately 1,000 patients, including patients with more complex coronary artery disease. Abbott’s bioresorbable technology delivers everolimus, an anti-proliferative drug. ————————————————————

Economic Model Suggests That the Use of Cypher in Diabetic Patients May Result in Substantial Cost Savings When Compared to Other DES

New analysis indicates that the broad use of Cypher^® sirolimus-eluting coronary stent in patients with diabetes would result in substantial cost savings, as compared to the use of everolimus-eluting stents (EES), paclitaxel-eluting stents (PES), or zotarolimus-eluting stents (ZES). According to this analysis, the cost reduction per diabetic patient treated with Cypher would range between $733 and $937, depending on the comparator drug-eluting stent (DES). When this analysis is extrapolated to an estimated 200,000 U.S. diabetics that undergo percutaneous coronary intervention (PCI) with DES implantation each year, the annual cost savings with Cypher would exceed $145 million vs. all three other DES (EES, PES, or ZES). This study reflects the growing attention to Comparative Effectiveness Research, a focal issue in the recent health care reform debate. “This study adds to the large body of evidence assessing the economic value of drug-eluting stents,” said Ryan Saadi, MD, MPH, Worldwide Vice President of Health Economics and Strategic Pricing at Cordis. “It is unique in that it includes all relevant stents and predicts the actual costs for an entire population of patients, in this case diabetic patients that qualify under a fixed fee reimbursement system like Medicare. We look forward to presenting our analysis in other important patient sub-groups in the future.” The analysis was based on the rates of target lesion revascularization (TLR) at 1 year among 4,853 patients with diabetes in 13 head-to-head clinical trials of various DES, all of which included the PES. When outcomes from these trials are combined using an indirect comparisons framework, the rate of TLR at 1 year in diabetic patients treated with PES was estimated to be 6.9%. The use of either EES or ZES was not associated with a significant relative risk reduction in 1-year TLR vs. PES. The 1-year TLR rates were estimated to be 7.9% for EES and 7.1% for ZES). In contrast, the use of Cypher led to a highly significant, 54% relative risk reduction in the rate of 1-year TLR (3.2%) vs. the PES (p————————————————————

Novel Drug-Eluting Stent System for Treatment of Small Vessels Demonstrated Safe and Effective at Eight Months

Biosensors International Group, Ltd announced 8-month results from the CARE II Study, which showed that its novel Sparrow^® drug-eluting stent system, developed by recently-acquired CardioMind, Inc., is both safe and effective in the treatment of small-vessel lesions. These results were presented by the Principal Investigator, Dr. Alexandre Abizaid, Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil, at the TCT. The Sparrow drug-eluting stent system combines a limus drug in a fully biodegradable polymer matrix with a self-expanding ultra-thin nitinol stent, mounted within a 0.014-inch guide wire delivery system. Due to its “stent-on-the-wire” construction, Sparrow has been developed as 60% smaller than the nearest available coronary stent system. Stent deployment is achieved through a novel release mechanism that utilizes electrochemical dissolution. The CARE II trial included 138 patients with single de novo native coronary artery lesions with a diameters between 2.00 mm and 2.75 mm and lengths up to 20 mm, randomized to receive either the Sparrow limus-eluting stent (DES), Sparrow bare-metal stent equivalent (BMS), or the established MicroDriver^® BMS designed for small vessel use. The trial’s primary endpoint was in-stent late loss at eight months. Average in-stent late loss in patients treated with the Sparrow DES was 0.29 mm, compared with 0.86 mm in patients treated with the Sparrow BMS, and 0.99 mm in patients treated with the MicroDriver. The difference was statistically significant in both cases (Sparrow DES vs. Sparrow BMS: p=0.0001; Sparrow DES vs. MicroDriver: p————————————————————

Zilver^® PTX^® DES Meets Its Primary Endpoint in a 479-Patient, Multi-Center, Pivotal Clinical Trial

A summary of the final clinical trial results for the randomized study of Cook Medical’s Zilver^® PTX^® drug-eluting peripheral stent for use in patients with peripheral arterial disease (PAD) in the superficial femoral artery (SFA) was presented at TCT. The study — from the largest clinical trial to ever evaluate the performance of a drug-eluting stent (DES) in the treatment of peripheral vascular disease — met its 12-month primary endpoint goals showing non-inferior event-free survival (EFS) and superior patency for the Zilver PTX as compared to balloon angioplasty. Cook Medical has developed Zilver PTX: a self-expanding, highly durable nitinol stent that uses a proprietary technology to deliver a locally therapeutic dose of paclitaxel to the target lesion. The data from this clinical trial supports Cook’s PMA application submitted to the FDA earlier this year. This multicenter, multinational, prospective, randomized study compared the safety and effectiveness of the Zilver PTX to balloon angioplasty and bare metal stenting. Patients with de novo or restenotic SFA lesions were randomized to balloon angioplasty or Zilver PTX stent placement. Balloon angioplasty patients experiencing acute failure (>30% residual stenosis) underwent secondary randomization to provisional stenting with Zilver BMS (bare metal stent) or Zilver PTX. Endpoints included event-free survival, stent integrity by radiographic core laboratory analysis, and primary patency by Duplex ultrasound core laboratory analysis (peak systolic velocity ratio 55 institutions in the United States, Japan and Germany), with 241 patients randomized to the Zilver PTX group and 238 to the balloon angioplasty group. Demographics and lesion characteristics were similar for both groups. Approximately half the balloon angioplasty group experienced acute failure and underwent secondary randomization, assigning 59 and 61 patients to provisional stenting with Zilver BMS and Zilver PTX, respectively. The study met its 12-month primary endpoint by showing non-inferior event-free survival and superior patency for the Zilver PTX compared to balloon angioplasty. There was also significant clinical improvement in the group receiving Zilver PTX. The Zilver PTX stent was CE Marked in August 2009 and has been made available in Europe since September of 2009. In the United States, the Zilver PTX DES is an investigational device not available for sale at this time. ————————————————————

Early Transcatheter Valve Recipient Honored With Courageous Patient Award At TCT 2010

Lillian Feldshuh, of Scarsdale, NY, an early recipient of a transcatheter aortic valve in 2006, received the Courageous Patient Award at the Transcatheter Cardiovascular Therapeutics (TCT 2010) scientific symposium in Washington, DC. The procedure was a success and Feldshuh, who will turn 100 years in just 7 months, remains in good health. In 2006, Lillian Feldshuh suffered from aortic stenosis. Even though she had been told there were no options, the team at NewYork-Presbyterian Hospital/Columbia University Medical Center, led by Dr. Martin B. Leon, performed percutaneous aortic valve replacement on the then 95-year-old woman. On September 23rd, that team presented her with the award. Mrs. Feldshuh was accompanied to Washington by her children, Broadway actress Tovah Feldshuh and playwright and physician David Feldshuh. She delivered her acceptance remarks to an audience of over 3,000 physicians. “In June 2006, I was given the choice to die or take the chance to live. Naturally, I chose to take the chance to live. Maybe I’m a pioneer, I don’t know. But I accept this award with gratitude and wonder. Who could have predicted in 1911 that in my hundredth year I would be receiving an award from the finest doctors in the world? I’ve had a blessed life. To reach this time and these years and be with you today, life is wonderful. I thank you from the bottom of my heart,” Feldshuh said.

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