Selected News from the American College of Cardiology Annual Scientific Sessions:March 24-27, 2007, New Orleans, Louisiana

SPIRIT III Clinical Trial Demonstrates Positive Performance for Both Taxus® and Promus Drug-Eluting Stent Systems Results of the pivotal SPIRIT III clinical trial reaffirmed prior safety and efficacy data for the Taxus® Express2 Paclitaxel-Eluting Coronary Stent System and provided early positive data for the Xience V (Promus) Everolimus-Eluting Coronary Stent System. The Xience V Everolimus-Eluting Coronary Stent System is manufactured by Abbott and distributed on a private-label basis by Boston Scientific as the Promus Everolimus-Eluting Coronary Stent System. Results of the U.S.-based, non-inferiority trial were presented at the annual American College of Cardiology Scientific Session in New Orleans. This trial is important as it reinforces our understanding of the proven performance of the Taxus Stent and generates enthusiasm for the early clinical data of this deliverable Olimus, the Promus Stent," said Martin B. Leon, MD, of Columbia University Medical Center and the Cardiovascular Research Foundation, New York. Gregg W. Stone, MD, the trial’s Principal Investigator, reported that the primary endpoint of angiographic in-segment late loss at eight months met its non-inferiority margin between the Taxus Stent (0.28 mm) and Xience V (Promus) Stent (0.14 mm), pNIPairing Medical Therapy with Coronary Intervention Fails to Reduce Heart Disease Deaths: COURAGE Results No study has examined the ability of percutaneous coronary intervention (PCI) to improve outcomes over and above modern, optimal medical therapy (OMT) in patients with stable coronary disease, until now. Results of research presented at the American College of Cardiology’s 56th Annual Scientific Session showed that PCI combined with OMT was no more effective than OMT alone in preventing myocardial infarction (MI) and other cardiac events among patients with coronary artery disease. The Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial enrolled 2,287 patients at 50 hospitals in the United States and Canada, randomizing them to one of two study arms: PCI and OMT together or OMT alone. Enrolled patients suffered from angina pectoris and had at least a 70% blockage of one or more coronary arteries. Both groups of patients received OMT, which includes guideline-driven intensive treatment with medicines such as aspirin, statins, antiplatelets, nitrates, ACE inhibitors, beta-blockers and calcium channel blockers, as well as lifestyle programs such as smoking cessation, exercise and weight control, and nutrition counseling. A majority of the patients in the study were men (85%) and had experienced chest pain for about two years, with an average of 10 episodes per week (median three episodes per week). Most exhibited several risk factors for heart disease: 29% were smokers, 67% had hypertension, 38% had a prior heart attack, 71% had high cholesterol, 27% had previous PCI and 69% had multi-vessel coronary artery disease. Approximately half of the patients met criteria for metabolic syndrome. Patients in the study group underwent PCI to clear the affected artery or arteries. Dr. William Boden at Buffalo General Hospital/Kaleida Health in Buffalo, New York and his collaborating investigators followed patients for two-and-a-half to seven years, with a primary endpoint of a death or a non-fatal MI. Results of the study showed a similar rate of death, MI or stroke. There were 211 primary events in the PCI group and 202 events in the medical therapy group. The 4.6-year cumulative primary rates of death or non-fatal MI were 19.0% and 18.5% in the PCI and medical therapy groups, respectively. Hospitalization rates for acute coronary syndrome were similar for both groups as well, at 12.4% and 11.8%, respectively. There was no statistically significant difference between the rates of MI: 13.2% in PCI plus OMT patients and 12.3% among OMT alone. The one benefit found for the PCI group was less angina compared with the medical therapy group, suggesting that while, on average, PCI does not allow patients to live longer or reduce their chances for a MI, it does improve their symptoms and quality of life. Conventional wisdom would indicate that PCI and OMT together would be superior to OMT alone. Indeed, that was our initial hypothesis, said Dr. Boden, lead investigator of the study, which was supported by the Department of Veterans Affairs. But results of the COURAGE trial demonstrate that two treatments are not always better than one. These findings, along with data from recent studies of more than 5,000 patients combined, show that PCI has no impact on reducing major cardiovascular events. BRIT Introduces PACS with 3D Cardiovascular Applications BRIT Systems launched its 3D cardiovascular applications as part of their PACS, The Roentgen Files, at the American College of Cardiology (ACC) 56th Annual Scientific Sessions. With the solution, all authorized cardiologists and radiologists have access to 3D imaging applications at multiple locations virtually anywhere, at any time. This new functionality is the result of a recently announced strategic partnership between BRIT and Mercury Computer Systems that integrates the Mercury Visage CS Thin Client Server into BRIT’s PACS and workstations. Mercury will also deliver professional services to BRIT to provide fast time-to-market turnkey solutions for implementing the thin client into BRIT's Linux Workstation. Through the use of a Linux client, Mercury’s 3D tools will become an integrated part of our workstation, BRIT Vision, said Shelly Fisher, President of BRIT Systems. This provides our application with a tremendous increase in capabilities for supporting features such as 3D and 4D rendering of images, coronary artery analysis and left ventricular wall analysis. Plus, these features can also be made available on Windows platforms for referring physicians through thin client technology without the facility incurring any additional expense. The continued prevalence of multi-slice CT (MDCT) and increased use of MRI for cardiac imaging prompted BRIT to also introduce a new set of PACS-native 3D tools. Improved and more powerful MPRs, MIPs, volume rendering and basic 3D imaging tools, along with more efficient viewing tools, are now native applications on all properly configured BRIT Vision workstations. BRIT’s advanced cardiovascular PACS applications will be available for deployment in May 2007. BRIT Systems is a technology company founded in 1993 that provides solutions for PACS, RIS and teleradiology. Modular systems are built using commercial off-the-shelf hardware and software based on standards such as DICOM-3 and HL-7. BRIT also provides services for archiving and accessing exams via Virtual Private Network that meet HIPAA’s security regulations. More information can be found at www.brit.com. CryoPlasty® Provides Alternative to Amputation for Patients with Blocked Arteries Below the Knee BTK CHILL study demonstrates high rate of limb protection at one year Boston Scientific Corporation announced one-year results from its Below-The-Knee (BTK) CHILL study, which evaluated the performance of the PolarCath Peripheral Dilatation System for the dilatation of stenotic lesions in infrapopliteal arteries when treating the whole leg. Results were presented by principal investigator Tony Das, MD, Director of Peripheral Interventions at Presbyterian Heart Institute of Dallas at the annual American College of Cardiology Scientific Session in New Orleans. One-year results of the BTK CHILL study, a prospective, multi-center trial with 111 limbs treated in 108 patients at 16 sites in the United States, include an 85% freedom from amputation rate and a 97% procedural success rate (a decrease in vessel narrowing to less than 50%), resulting in improved blood flow. These outcomes are particularly encouraging in light of the severity of disease in these patients. The majority of patients in this study exhibited tissue loss at baseline with nonhealing ulcers or focal tissue loss reported in 66% of the limbs and gangrene reported in 37% of the limbs (some patients reported both focal tissue loss and gangrene). In total, 69% of the treated limbs were categorized as either Rutherford Class 5 or 6 at the time of study enrollment. Almost 70% of patients with critical limb ischemia undergo amputation as the initial treatment, said Dr. Das. The 12-month results from the BTK CHILL study support the effectiveness of the PolarCath System, which offers a valuable alternative to amputation or invasive surgical bypass procedures in patients who have this painful, historically difficult-to-treat condition. CryoPlasty therapy using the PolarCath Peripheral Dilatation Device is a form of balloon angioplasty that cools the inside of blocked arteries in the legs while opening them up. This technology uses nitrous oxide to fill an angioplasty balloon within a blocked artery, cooling the balloon’s surface to -10 degrees C. As it is inflated, the cold surface of the balloon cools the vascular lesion, which exerts both mechanical and biological effects that may help prevent re-blockage of the artery. Mechanically, CryoPlasty therapy may enhance the uniformity of lesion dilatation, reducing injury during the procedure. Cooling may also help to prevent vessel and lesion recoil. Biologically, cooling promotes a process called apoptosis, which may reduce excessive thickening of the new layer of smooth muscle cells which contributes to restenosis. Procedures using the PolarCath Peripheral Dilatation System are typically completed in just a few hours and may relieve pain and symptoms. First Human Trial Tests Stem-Cell-Based Treatment for MI Despite the enduring controversy surrounding the use of embryonic stem cells for disease research, scientists continue to evaluate the therapeutic potential of other types of stem cells. Previous research on the efficacy of stem cell therapy for heart repair has shown possible benefit from mesenchymal stem cells (MSCs) cells found in bone marrow that create connective tissue, bone and cartilage. A study presented at the American College of Cardiology’s Innovation in Intervention: i2 Summit reveals the results of the first human trial using MSCs for the treatment of myocardial infarction (MI). As a cell-based therapy, MSCs have a number of unique advantages: they can be taken from genetically distinct donors, are easy to prepare, and have a tendency to collect within injured areas. In animal models, MSCs not only home to regions of MI, but reduce infarct size and improve ejection fraction. Researchers from ten medical centers across the United States, led by Joshua Hare, MD, of the University of Miami, Miller School of Medicine, conducted a Phase 1 trial to assess the safety and efficacy of infusing MSCs intravenously to 53 patients within ten days of a MI. In the trial, patients were randomized to one of three doses: 0.5, 1.6 or 5 million MSCs/kg, and each dose was compared with placebo. The occurrence of treatment-related serious adverse events was evaluated over a six-month period, and efficacy was assessed using echocardiography. Over the six month follow-up period, the stem cell-treated patients had lower rates of side effects such as cardiac arrhythmias, and had significant improvements in heart, lung and global function. Echocardiography showed improved heart function, particularly in those with large amounts of cardiac damage. This trial makes an important contribution in the field of stem cell-based treatments for heart disease by providing safety and efficacy data for a unique and promising type of stem cell to treat cardiac damage, said Joshua Hare, MD, of the University of Miami and lead author of the study. It’s important to note that this study represents a first step, and, as in other disease categories, we must perform additional, larger trials to determine the real world application of mesenchymal stem cell therapy to fight heart disease. Abbott Announces Positive Six-Month Results from Clinical Trial of Fully Bioabsorbable Drug-Eluting Coronary Stent Abbott announced positive results from ABSORB, a clinical trial evaluating the overall safety and performance of a fully bioabsorbable drug-eluting stent platform for the treatment of coronary artery disease. Six-month results from the first 30 patients in the trial, presented at the 56th Annual American College of Cardiology Scientific Session in New Orleans, demonstrated no stent thrombosis and a low (3.3%) hierarchical rate of ischemia-driven major adverse cardiac events (MACE), such as heart attack or repeat intervention. The encouraging results from the first 30 patients of ABSORB suggest that drug-eluting bioabsorbable stent technologies may be a promising future therapy option for physicians treating patients with heart disease, said Patrick W. Serruys, MD, PhD, professor of interventional cardiology at the Thoraxcentre, Erasmus University Hospital, Rotterdam, who is co-principal investigator of the study. The single MACE event reported was a non-Q-wave myocardial infarction. The same patient underwent a repeat intervention that occurred at the site of the original procedure, resulting in an overall target lesion revascularization rate of 3.3%. The trial results confirmed that the treatment effect of everolimus in the bioabsorbable stent is similar to that observed in Abbott’s studies of metallic drug-eluting stents, with everolimus actively inhibiting tissue growth into the artery. The rate of device success (successful placement of the bioabsorbable stent at the site of the lesion) was 93.5%. Abbott’s everolimus-eluting bioabsorbable stent is made of polylactic acid, a proven biocompatible material that is commonly used in medical implants such as dissolvable sutures. Unlike a metallic stent, a bioabsorbable stent is designed to be slowly metabolized by the body and completely absorbed over time. The ABSORB trial is a prospective, non-randomized (open label) study designed to enroll up to 60 patients in Belgium, Denmark, France, New Zealand, Poland and The Netherlands. Key endpoints of the study include assessments of safety MACE and stent thrombosis rates at 30, 180 and 270 days, with an annual follow-up for up to five years, and successful deployment of the bioabsorbable drug-eluting stent. Other key endpoints of the study include follow-up measurements assessed by angiography, IVUS, and state-of-the-art imaging modalities at 180 days and two years, as well as a new noninvasive technique in a subset of patients at 18 months. The co-principal investigator of the study is John Ormiston, MD, of Mercy Hospital in Auckland, New Zealand. Study Identifies Steps to Improve Safety of Renal Artery Stenting Platelet Inhibitor Combined with Embolic Protection Device Yields Best Results High blood pressure is the most common chronic medical condition in the United States, and the most common identifiable cause is renal artery stenosis. Renal artery stenting is a widely performed but controversial procedure for patients with narrowed kidney arteries. Studies have demonstrated little improvement in average kidney function with a significant minority of patients experiencing a decline in kidney function after the procedure. Use of a platelet inhibitor may make renal artery stenting safer for patients, especially when used in combination with an embolic protection device (EPD), according to a study presented at the American College of Cardiology’s Innovation in Intervention: i2 Summit in New Orleans. This is the first study to test whether using glycoprotein IIb/IIIa inhibitors and EPDs would improve renal function following the stenting. To test the value of the combination therapy regimen, a total of 100 patients undergoing renal artery stenting at seven centers were randomized to an EPD (Angioguard) or double-blinded use of a glycoprotein IIb/IIIa inhibitor (abciximab) in a 2x2 factorial design. Patients’ key functions were recorded, including kidney function, activation of platelets and the presence of platelet-rich thrombus in the filter baskets of the EPDs. The main effects of treatments and their interaction were assessed by percent change in MDRD-derived GFR from baseline to one month. MDRD-derived GFR (glomerular filtration rate) is a widely accepted estimated measure of kidney function, usually based on serum creatinine level, age, sex and race. Researchers found that an overall improvement in renal function was only observed in patients allocated to both treatments. Abciximab reduced the occurrence of platelet-rich emboli (particles or debris) in the EPD from 42 to seven percent. This difference was highly significant compared to the three other possible allocations in the 2x2 design. EPD alone was not associated with improved renal function, whereas the use of a glycoprotein IIb/IIIa inhibitor showed measurable benefit. When examined independently, the platelet inhibitor abciximab appeared to have beneficial effects, but Angioguard did not appear to be noticeably helpful, said Christopher J. Cooper, MD, of the University of Toledo and lead author of the study. However, the group treated with both Angioguard and abciximab in combination benefited the most from treatment, illustrating a significant interaction effect. Like many other studies, we are finding that patients benefit from a combination of therapeutic strategies; in this case, the filter and the drug serve patients best when doctors use both in combination.

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