News from the American College of Cardiology Annual Scientific Session 2005

Heartlab Introduces Ascentia, a Full Web-based Cardiovascular Information System and Announces OEM Distribution of TomTec 3D/4D Clinical Application Package Heartlab previewed its new Ascentia cardiovascular information system at the 54th Annual Scientific Session of the American College of Cardiology in Orlando. The Ascentia line provides a complete package of multimodality image analysis tools, comprehensive digital reporting, and secure portal access to patient records delivered via a web-based technology that improves access and reduces system administration. Using new approaches to system architecture, Ascentia Portal delivers full diagnostic quality DICOM images to virtually any PC on the inter/intranet. Heartlab’s new compression-on-demand technology delivers over 10 different levels of lossless and lossy compression on the fly directly from the original images in the DICOM archive. Storing additional compressed copies of images has been totally eliminated. Ascentia WorkStation enables access to diagnostic-quality images and review tools for multiple cardiology and vascular imaging exams. WorkStation introduces new user-configurable measurement protocols and vascular features such as bolus chase reconstruction and remasking. Ascentia Results Management offers integrated, structured reporting which allows physicians to create reports digitally while reviewing cases online. The repository of cardiology image data can be mined quickly and easily, transforming clinical data into meaningful information for statistical analysis, research and presentations. Also, as a work-in-progress, Heartlab showed the Ascentia HeartStation to handle digital ECG management for electrocardiograms from any vendor’s ECG equipment. With HeartStation, ECG studies are stored, read, interpreted and archived as part of a patient’s web-accessible electronic medical record. The HeartStation combines a dynamic new user interface with image acquisition and analysis algorithms for versatile, vendor-neutral, enterprise-wide ECG management that promotes paperless workflow for cardiology. Heartlab’s Ascentia WorkStation, Results Management, and Portal systems received FDA 510(k) clearance on February 18, 2005. Heartlab, Inc. also has announced that it has signed an agreement with TomTec Imaging Systems GmbH to distribute its 3D/4D clinical application package, called 4D Cardio-View, as an integrated component of the Ascentia WorkStation. TomTec’s software capabilities in 3D and 4D analysis, reconstruction, rendering and advanced quantification will be made available within the Ascentia WorkStation application. Instead of launching a separate application from the desktop, the TomTec technology will be instantly available to users within the Ascentia WorkStation application. The TomTec clinical application package enables Heartlab software to work with proprietary formats from other vendors. With the new integrated, offline solution, physicians will be able to perform analysis functions from the Ascentia WorkStation on the hospital network. TAXUS V Results Reported Boston Scientific Corporation announced nine-month results from its TAXUS V clinical trial, confirming the safety and efficacy of the TAXUS® Express2 paclitaxel-eluting coronary stent system for the treatment of coronary artery disease. The Company said that the overall TAXUS V study met its primary endpoint as well as all secondary endpoints. TAXUS V expands on the TAXUS IV pivotal trial by studying a higher-risk patient population, including patients with small vessels, large vessels and long lesions requiring multiple overlapping stents the most challenging lesions and highest-risk patients ever studied in a randomized, controlled drug-eluting stent trial in the United States. The Company made the announcement at the annual American College of Cardiology scientific session in Orlando. The randomized, double-blind trial enrolled 1,172 patients at 66 sites in the United States, assessing the safety and efficacy of a slow-release formulation paclitaxel-eluting coronary stent system in reducing restenosis in de novo lesions 10-46 mm in length and 2.25-4.0 mm in diameter. Safety data. The results supported safety as demonstrated by low overall rates of Major Adverse Cardiac Events (MACE) and stent thrombosis. MACE includes death, myocardial infarction (MI; Q-wave and non-Q-wave) and target vessel revascularization (TVR). The study reported a 15.0 percent overall MACE rate at nine months in the TAXUS group compared with 21.2 percent in the control bare-metal stent group (p=0.0084), with all other factors, including cardiac death and MI, comparable to control (cardiac death was 0.5 percent in the TAXUS group versus 0.9 percent in the control group (p=0.7256), MI was 5.4 percent in the TAXUS group versus 4.6 percent in the control group (p=0.5853)). The MACE reduction was due to the lower target lesion revascularization (TLR) rate in the TAXUS group compared with the control group. In addition, stent thrombosis rates were identical between TAXUS and control stents (0.7 percent or 4/557 patients in the TAXUS group versus 0.7 percent or 4/562 patients in the control group), indicating comparable safety of drug-eluting stents and bare-metal stents. Revascularization rates. The study reported a total lesion revascularization rate (TLR) of 8.6 percent in the TAXUS group compared with 15.7 percent in the control group (P= 0.0003). TLR is one of the most accurate indicators of the performance of drug-eluting stent technology. The study met its primary endpoint, nine-month TVR (symptom-driven repeat revascularization of the target vessel), which was significantly lower in the TAXUS group (12.1 percent) than in the control group (17.3 percent) (p=0.0184). Restenosis rates. The study reported an in-segment (stented vessel segment plus 5 mm beyond each end of the stent) binary restenosis rate of 18.9 percent in the TAXUS group compared with 33.9 percent in the control group (P less than 0.0001) (binary restenosis is defined as 50 percent or greater vessel re-occlusion). The study reported an in-stent binary restenosis rate of 13.7 percent in the TAXUS group compared with 31.9 percent in the control group (P less than 0.0001). In addition, the study found significant improvements in the more sensitive, quantitative angiographic measurements (in-segment, in-stent and at the edges), such as in-segment percent diameter stenosis (33.63 percent in the TAXUS group versus 42.34 percent in the control group; P less than 0.0001), in-segment minimum lumen diameter (1.81 mm in the TAXUS group versus 1.57 mm in the control group; P less than 0.0001) and in-segment late lumen loss (0.33 mm in the TAXUS group versus 0.60 mm in the control group; P less than 0.0001). TAXUS V studies a challenging patient population with multiple, concurrent risk factors including small vessels and long lesions requiring multiple stents, which has never before been studied with drug-eluting stents, said Gregg W. Stone, MD, the study’s Principal Investigator and Professor of Medicine, Columbia University Medical Center in New York. The overall study shows TAXUS stents are safe, with comparable rates of death, MI and stent thrombosis between TAXUS and bare-metal stents. The study further shows the product is highly effective, with marked reductions in clinical and angiographic parameters. While there was a small but elevated rate of non-Q-wave MI in TAXUS patients receiving multiple overlapping stents compared to control, this was most likely related to reductions in side branch blood flow and balanced by the reduction in reintervention of more than 50 percent in the TAXUS group. These are compelling findings that further confirm the safety outcomes of paclitaxel-eluting stent technology compared to bare-metal stents, said Stephen G. Ellis, MD, the trial’s Co-Principal Investigator and Director of the Sones Cardiac Catheterization Laboratories at the Cleveland Clinic. The overall MACE rates are particularly low for such a complex set of patients. Mennen Medical and ScImage Announce International Business Partnership Combined Hemodynamic and Cath Lab Imaging Solution Mennen Medical Corp., the advanced hemodynamic monitoring manufacturer, and ScImage, Inc., The Enterprise PACS Company, announced a business partnership at the Annual Scientific Session of the American College of Cardiology for the integration and co-marketing of their cardiology products as a complete, seamlessly integrated solution. The combined offering will deliver a range of features, including the live viewing of prior images during cath lab procedures as well as fully integrated multi-modality DICOM worklists. Under the agreement, the two companies will both offer the new integrated digital hemodynamic multi-modality for sale throughout the U.S. Mennen will sell the integrated solution internationally under its own name. Studies Find Aspirin Resistance in up to 27% of Aspirin Users Highest Incidence Among Women, Elderly and Low-Dose Patients; Link to Plavix Resistance Also Revealed Up to 27 percent of patients with well-documented CAD on an aspirin regimen for at least four weeks were found to be resistant to aspirin’s antiplatelet effects, determined by the Accumetrics VerifyNow Aspirin test, according to research reported by Dr. W.H. Chen and colleagues at the University of Hong Kong at the American College of Cardiology meeting. The study of 468 patients identified patient characteristics significantly associated with increased risk for the condition. Women, the elderly, those with renal insufficiency, low hemoglobin levels and those taking low-dose aspirin were found to have the highest likelihood of being aspirin resistant. In particular, the authors identified that dosage of aspirin directly correlates with the prevalence of aspirin resistance. The highest prevalence of aspirin resistance was associated with doses of less than 100 mg (30.2%), was less prevalent in higher aspirin doses of 150 mg (16.7%), and non-existent with 300 mg (0%). Separately, a meta-analysis of 200,000 people also presented at the ACC meeting showed that risk of bleeding increases with increasing doses of aspirin (especially 325 mg). In combination, these two studies suggest that a balance between safety and effectiveness needs to be achieved so that the lowest, effective dose is prescribed and patients are confirmed responsive to their aspirin regimen. Knowledge of particular patient groups susceptible to aspirin resistance underscores the need to confirm aspirin response so that alternative or additional antiplatelet therapy can be considered in this population at higher risk, said Daniel Simon, associate director, interventional cardiology at Brigham and Women’s Hospital and professor of medicine at Harvard University. Physicians don’t use coumadin or heparin without monitoring their anti-thrombotic effects. Antiplatelet therapy is no different. It is clear that the individual patient responds differently and one dose does not fit all. Another study demonstrated that resistance to aspirin and clopidogrel (or Plavix®) may often occur together, according to research presented by Dr. Eli Lev and colleagues at Baylor College of Medicine in Houston. In fact, 50% of those patients resistant to aspirin were also resistant to clopidogrel. Using the VerifyNow Aspirin test, the study evaluated 80 patients who had received aspirin for at least a week, finding 15% to be aspirin resistant. Separately, 24% of patients were found to be resistant to clopidogrel. A total of 7.5% of patients in the study were resistant to both aspirin and clopidogrel. This research suggests that a positive test for aspirin resistance raises the possibility that the patient may be clopidogrel resistant as well, said Dr. Lev. The VerifyNow Aspirin test is a rapid, point-of-care blood test that measures the degree to which a patient’s platelets aggregate. The U.S. FDA has granted a waiver under the Clinical Laboratory Improvements Amendments of 1988 (CLIA) for the VerifyNow Aspirin test. The waiver places the VerifyNow Aspirin test among the least complex of laboratory tests, in the same category as many cholesterol and coagulation tests. The VerifyNow Aspirin test is the first platelet function assay to receive CLIA waived categorization and no longer requires the specialized procedures of moderately complex CLIA laboratories. The new FDA classification expands the availability of the VerifyNow Aspirin test to a wider physician community, in addition to the hospital and laboratory setting. The test provides a result in 30 minutes and gives one number indicating whether aspirin is effectively inhibiting platelet function or if a patient is resistant. The VerifyNow Aspirin test can be performed in the physician office. The test is also available at hospitals and laboratories throughout the country and is eligible for reimbursement by Medicare as well as by private insurance providers. Clinical Results of ENDEAVOR II Trial Presented William Wijns, MD, the Co-Principal Investigator of the ENDEAVOR II Pivotal Clinical Trial and Co-Director of the Cardiovascular Center, OLV Ziekenhuis, Aalst, Belgium, presented positive results of the ENDEAVOR II trial at the American College of Cardiology (ACC) 54th Annual Scientific Session. The ENDEAVOR II study demonstrated clinically and statistically significant improvement in all of the study’s endpoints, including a 47 percent reduction in the primary endpoint of Target Vessel Failure (TVF). Overall the clinical results show that more than 95 percent of the patients who received an Endeavor stent in the trial required no further treatment or revascularization at the original treatment site at the nine month assessment period, said Dr. Wijns. The Endeavor stent’s performance in this trial provides substantial evidence that the Endeavor drug eluting stent is safe and that it substantially reduces clinical restenosis compared to a bare metal stent. The ENDEAVOR II Clinical Trial, sponsored by Medtronic, Inc., was a randomized, double-blind pivotal trial designed to evaluate the safety and efficacy of Medtronic’s Endeavor Drug Eluting Coronary Stent compared to Medtronic’s Driver® Cobalt Alloy Coronary Stent in patients with coronary artery disease. The co-principal investigators of the ENDEAVOR II trial are Dr. Wijns; Jean Fajadet, MD, Clinique Pasteur Unite de Cardiologie Interventionnelle, Toulouse, France; and Richard M. Kuntz, MD, Associate Professor, Harvard Medical School; and Chief, Division of Clinical Biometrics, Brigham and Women’s Hospital, Boston. The trial enrolled 1,197 patients at 72 facilities in 17 countries, making it the first and largest drug-eluting stent trial comparing a drug eluting stent to a bare metal stent ever performed outside the U.S. The primary endpoint of the trial was TVF at nine months. TVF is a composite endpoint, which includes death, myocardial infarction and Target Vessel Revascularization (TVR). The study successfully met its primary and secondary endpoints, including a 47 percent reduction in TVF in the Endeavor arm (8.1%) in comparison with the control group (15.4%). The study also demonstrated a 62 percent reduction in Target Lesion Revascularization (TLR) between the Endeavor arm (4.6%) and the control group (12.1%). Angiographic results of the study demonstrated a significant reduction in restenosis rates. The study showed a 71 percent reduction in in-stent angiographic binary restenosis (ABR) in the Endeavor arm (9.5%) versus the control arm (32.7%). The in-segment ABR rate in the study was reduced by 61 percent in the Endeavor arm (13.3%) versus the control arm (34.2%). The study showed an in-segment late loss of 0.36 mm in the Endeavor arm (0.70 mm in the control arm) and an in-stent late loss of 0.62 mm in the Endeavor arm (1.03 mm in the control arm). Dr. Kuntz said, The study had an impressive 88 percent follow up rate in the assigned angiographic cohort and a 97 percent follow up rate in the clinical cohort. The study indicated a 50 percent reduction in the Major Adverse Cardiac Event (MACE) rate in the Endeavor arm (7.4%) compared to the control arm (14.7%). In addition, the ENDEAVOR II trial showed a 0.5 percent rate of stent thrombosis at 30 days with no late thrombosis beyond 30 days and no late stent malapposition. Martin B. Leon, MD, co-principal investigator of the ENDEAVOR III and ENDEAVOR IV Clinical Trials and Chairman of The Cardiovascular Research Foundation, Columbia University Hospital, New York, said. While you get a significant treatment effect with drug eluting stents, we must always remain diligent that long-term safety is not compromised in patients. The ENDEAVOR II clinical experience of zero thrombosis beyond thirty days and no late malapposition places the Endeavor stent among the safest DES systems studied to date. The Endeavor drug eluting stent is based on the Driver Coronary Stent. The Driver stent is made of a cobalt alloy and has a modular architecture to provide deliverability over standard bare metal stents. Dr. Wijns added, Device and lesion success rates were all above 99 percent in both the Endeavor arm and Driver control. Caution: The Endeavor Drug Eluting Coronary Stent is an investigational device with an investigational drug (ABT-578) and exclusively for clinical investigation. Aggrastat® Injection ADVANCE Clinical Data Presented at ACC Guilford Pharmaceuticals Inc. announced the presentation of additional data from the ADVANCE trial (The Additive Value of Tirofiban Administered With the High-Dose Bolus in the Prevention of Ischemic Complications During High-Risk Coronary Artery Angioplasty) at the 2005 Scientific Sessions of the American College of Cardiology. The data, presented by Dr. Marco Valgimigli, showed that in this study a single high dose bolus (SHDB) regimen of Aggrastat® Injection (tirofiban hydrochloride) improved outcomes in diabetic patients undergoing percutaneous coronary intervention (PCI) when compared to placebo. Marco Valgimigli, MD, Chair of Cardiology, University of Ferrara, Italy, and principal investigator for the ADVANCE trial, commented, Diabetic patients are known to experience a higher rate of adverse ischemic events during and after PCI. One hypothesis is that this is a result of the differences in platelet physiology between diabetic and non-diabetic patients. Diabetic platelets are larger and demonstrate enhanced aggregation compared to non-diabetic platelets. We sought to determine whether tirofiban, administered as a SHDB regimen could reduce ischemic events in diabetic patients referred for elective or urgent PCI. The ADVANCE study was a double-blind, placebo-controlled, randomized trial that included 202 high-risk patients undergoing PCI. Patients in the placebo group were eligible to receive bail-out GP IIb/IIIa inhibitor therapy during PCI if deemed necessary by the investigator. In this PCI trial, 98% of patients underwent intracoronary stenting. The data presented were based on a prespecified subgroup analysis of 99 patients with diabetes who participated in the ADVANCE trial. On background therapy of heparin, aspirin and a thienopyridine (ticlopidine or clopidogrel), patients were randomized to receive the SHDB regimen of tirofiban (N=54; bolus of 25 mcg/Kg/3-min, followed by an infusion of 0.15 mcg/Kg/min for 24-48 h), or placebo (N=45). The primary endpoint was a composite of death, nonfatal myocardial infarction (MI), urgent target vessel revascularization and thrombotic bailout GP IIb/IIIa inhibitor therapy occurring within six months of PCI. After a median follow-up of 262 days (range: 143-398) the results yielded a significantly reduced primary composite endpoint with the SHDB regimen of tirofiban when compared to placebo (17% vs. 40%; HR 0.37 [95% CI: 0.11- 0.58]; p=0.003), with a relative risk reduction of 58%. The incidence of major and minor bleeding was not statistically different between the two groups. However, this lack of difference in adverse events could be due to the fact that the study was underpowered. The difference in the incidence of adverse ischemic events was mainly due to a lower rate of periprocedural MI in the tirofiban versus the placebo group (4% vs. 18%, p=0.048). In this study, the Investigators concluded that the SHDB regimen of tirofiban, by decreasing the incidence of ischemic complications, was both safe and effective, supporting the notion that diabetic patients, irrespective of their clinical status, would probably benefit from a tailored drug regimen during PCI. These findings were based on a limited and selected sample size, and thus should be viewed as preliminary. REALITY Trial Data Presented at ACC Results from the REALITY trial presented at the American College of Cardiology Annual Scientific Session found that the Cypher® sirolimus-eluting coronary stent was associated with development of significantly fewer stent thromboses than the Taxus paclitaxel-eluting coronary stent* (p=0.020). In this trial, compliance with dual anti-platelet therapy was extremely high (99 percent for the Taxus Stent vs. 97 percent for the Cypher Stent). "In this study, the incidence of stent thrombosis was 78 percent lower with the Cypher Stent than with the Taxus Stent," said Principal Investigator Marie-Claude Morice, MD, Head of Interventional Cardiology at the Institut Hospitalier Jacques Cartier, Massy, France. "As this is the first head-to- head trial to observe a difference in the rate of stent thrombosis, these results raise concerns and demand further investigation." The study also demonstrated that both Cypher Stent and Taxus Stent were equally deliverable. The study also demonstrated that both products were efficacious, at comparable rates, in preventing in-segment binary restenosis, which was the primary endpoint of the study, in moderately complex patients. "While we see that the two drug-eluting stents were comparable in terms of the primary endpoint of restenosis, we also observed that patients who received the Cypher Stent had a significantly larger vessel diameter inside the stent after eight months of follow-up," noted Dr. Morice. The REALITY trial is one of several randomized controlled trials, including the ISAR-DIABETES and SIRTAX studies, comparing the two drug-eluting stents in different patient populations that were presented during the international meeting. Sponsored by Cordis Corporation, a Johnson & Johnson company, the REALITY Trial is a prospective, randomized study involving 1,386 patients at 90 hospitals centers in Europe, Latin America and Asia. In the REALITY trial, patients were included if they had up to two de novo lesions with a primary lesion of at least 15 mm in length in small vessels (2.25 to 3.0 mm in diameter). The two study arms were well balanced in terms of standard patient characteristics including age, sex and prior heart attack. Patients were also well balanced in terms of number of diseased arteries and the location of the lesions. On average, patients receiving the Cypher Stent had 1.91 stents while those receiving Taxus had 1.94 stents. CLD

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