Clinical and Industry News

Extended Use of Clopidogrel in Patients with Drug-Eluting Stents Associated with Lower Risk of Death or MI For patients with drug-eluting stents who are event-free at six months follow-up, the extended use of clopidogrel is associated with a significant reduction in risk for death or myocardial infarction through 24 months after stent implantation, according to a study posted online and published in the January 10, 2007 issue of the Journal of the American Medical Association. Recent studies of drug-eluting intracoronary stents suggest that current antiplatelet regimens may not be sufficient to prevent late stent thrombosis, the study authors note. Instructions for the use of drug-eluting stents (DES) commercially available in the United States specify treatment with clopidogrel for at least three (for sirolimus-coated stents) or six months (for paclitaxel-coated stents) after implantation. Premature discontinuation of this minimum antiplatelet therapy has been strongly associated with stent thrombosis. Eric L. Eisenstein, DBA, and colleagues from Duke University Medical Center, Durham, NC, conducted an observational study of 4,666 patients who underwent initial percutaneous coronary intervention with a bare metal (3,165 patients) or drug-eluting stent (1,501 patients) between Jan. 1, 2000 and July 31, 2005 with follow-up contact at 6, 12 and 24 months through Sept. 7, 2006. The researchers used two landmarks in this study: at six and 12 months, the patients were asked if they were taking clopidogrel and if they were event-free (no death, myocardial infarction, or revascularization). Patients who were event-free were divided into one of four groups: drug-eluting stent with clopidogrel (DES + C), DES without clopidogrel (DES - C), bare metal stent with clopidogrel (BMS + C) and BMS without clopidogrel (BMS - C). The authors then determined whether patients had died or had nonfatal myocardial infarction between the landmark time and 24 months follow-up. Among patients with drug-eluting stents who were event-free at six months (637 with and 579 without clopidogrel), clopidogrel use was a significant predictor of lower rates of death (2.0 percent with vs. 5.3 percent without), and death or myocardial infarction (3.1 percent with vs. 7.2 percent without) at 24 months; however, among patients with bare metal stents (417 with and 1,976 without clopidogrel) there were no differences in death (3.7 percent with vs. 4.5 percent without), or death or myocardial infarction (5.5 percent with vs. 6.0 percent without), the researchers found. Among patients with drug-eluting stents who were event-free at twelve months (252 with and 276 without clopidogrel), clopidogrel use continued to predict lower rates of death (0.0 percent with vs. 3.5 percent without), and death or myocardial infarction (0.0 percent with vs. 4.5 percent without), at 24 months; however, among patients with bare metal stents (346 with and 1,644 without clopidogrel) there continued to be no differences in death (3.3 percent with vs. 2.7 percent without), or death or myocardial infarction (4.7 percent with vs. 3.6 percent without). By simultaneously comparing patients in four treatment groups defined by stent type and clopidogrel use, we found that patients with a drug-eluting stent receiving clopidogrel six and twelve months after their initial procedure have significantly lower rates of death and death or MI (myocardial infarction) compared with patients with a drug-eluting stent not receiving this medication, the authors write. However, the appropriate duration for clopidogrel administration can only be determined within the context of a large-scale randomized clinical trial, they conclude. Real-World Taxus® Stent Data Confirm Favorable Outcomes for Patients With Complex Coronary Artery Disease Boston Scientific Corporation presented data on its 7,000- patient ARRIVE I and II registries of real-world patients, including those with complex lesions, to a special U.S. Food and Drug Administration (FDA) panel. The data showed that the Taxus® paclitaxel-eluting coronary stent provides substantial benefits in keeping arteries open and avoiding repeat procedures for patients with complex coronary artery disease, at no higher risk than alternative cardiovascular treatments. The data were presented by Dr. Donald S. Baim, Chief Medical and Scientific Officer for Boston Scientific, during an advisory panel meeting assembled by the FDA in response to concerns about the incidence of late stent thrombosis in drug-eluting stents. Dr. Baim first appeared before the panel on December 8th, when he outlined data on Boston Scientific's long-term randomized clinical trials in 2,797 patients with somewhat less complex lesions. The data showed that the Taxus stent is as safe as bare-metal stents and far more effective in reducing the need for repeat procedures. While the TAXUS randomized clinical trials focused on patients who received a single stent to relieve blockage in a single vessel, the patients enrolled in the ARRIVE registries tended to present much more complex situations involving very small, very long or multiple vessel blockages that often required multiple stents. These patients represent up to two-thirds of the patients who receive Taxus stents in the real-world practice of interventional cardiologists. The data presented by Dr. Baim showed that patients in the ARRIVE registries with simple blockages had comparable outcomes to those with similar lesions in the TAXUS clinical trials, confirming the ability of these registries to accurately track clinical outcomes. As expected, patients with complex coronary artery disease had slightly higher adverse events compared to the randomized trials and the simpler cases in the ARRIVE registries. However, the rates of death and MI were equivalent or better than those for potential alternative treatments such as bypass surgery. The data on complex cases were also consistent with other real-world registries of drug-eluting stents using either the Taxus or Cypher® stent. These registries showed trends towards lower rates of death, MI, and repeat procedures for Taxus stents compared to Cypher stents, in patients with diabetes mellitus. The patients treated in ARRIVE had such complex disease that many would have been poor candidates for bare-metal stents or conventional angioplasty, said Dr. Baim. They were just too sick and the standard treatment for many of these patients would have been bypass surgery, yet the patients treated with the Taxus stent had similar or lower rates of death, heart attacks and repeat procedures than historically seen with bypass surgery. What the ARRIVE data show is that in complex, real-world cases, Taxus stents provided the benefits of keeping vessels open and reducing the need for repeat procedures, with rates of adverse events that were no worse, and in many cases better, than other alternative treatments, including bypass surgery, said Dr. Baim. He added that pending the results of randomized studies of even more complex cases, there is no reason to believe that current clinical use exposes complex patients to excess risk compared to other available revascularization therapies. The FDA panel, which will conclude two days of hearings on December 8th, first considered data involving approved uses of drug-eluting stents before moving to uses by interventional cardiologists for other kinds of cases, many of them involving complex heart disease or subsets like diabetic patients. In his earlier presentation to the panel, Dr. Baim reviewed four randomized Taxus clinical trials that compared the Taxus stent to bare-metal stents in 2,797 patients followed for four years. The detailed analysis of those data shows that under any and all definitions proposed for very late stent thrombosis, there was no statistically significant increase in stent thrombosis with the Taxus stent. The analysis also showed that the low rates of death and MI were essentially the same or lower for the Taxus stent compared to bare-metal stents. Moreover, the Taxus stent demonstrated a profound clinical benefit, with a sustained reduction of nearly 50 percent in repeat procedures compared to bare-metal stents. These favorable risk-benefit outcomes were seen in important trial subgroups, including patients with diabetes, small vessels and multiple stents per vessel. Enrollment is approaching completion in two additional landmark randomized trials comparing the Taxus stent to bare-metal stents in patients with acute MI and comparing the Taxus stent to bypass surgery in the most complex patients with narrowing of the left main coronary artery and/or narrowing of all three coronary arteries. Cordis Corporation Announces Clinical and Educational Programs for the Cypher® Sirolimus-Eluting Coronary Stent Cordis Corporation stated to an advisory panel to the U.S. Food and Drug Administration (FDA) that analysis of its research on the Cypher® Sirolimus-eluting Coronary Stent suggests a need for additional education on anti-platelet therapy regimens for bare-metal and drug-eluting stent patients and further research to understand safety factors. Further, Cordis Corporation committed to support efforts by the clinical community, medical societies and industry to achieve these goals. The company's conclusions are based on an independent analysis of long-term clinical data for the Cypher Stent. This independent analysis, conducted and presented by the Harvard Clinical Research Institute, confirmed that the safety and clinical benefits of the Cypher Stent extend out to four years. The data, based on four randomized controlled clinical trials, suggested that there was no significant difference in the incidence of thrombosis between the Cypher Stent and bare-metal stents. Since the initiation of the first pivotal clinical trial in support of product approval for the Cypher Stent, Cordis has included stent thrombosis as a clinical endpoint and continues this approach. In October, the company announced a study of the multiple factors that may lead to the condition and potential benefits of medical regimens. A patient registry, currently underway in Europe and Asia/Pacific, will now extend to the U.S. and will include a prospective randomized subset of 15,000 patients. This expanded registry will evaluate a variety of safety and efficacy measures, including the need for target lesion revascularization, major adverse cardiac events such as myocardial infarction (MI) and death, stent thrombosis, as well as detailed information about the use of dual anti-platelet therapy. Additionally, the company announced that it would extend follow up to eight years the SIRIUS, E-SIRIUS and C-SIRIUS clinical trials, which were each originally designed to end after five years. Together, the new registry and expanded clinical trials will provide ongoing information about the safety and efficacy of the Cypher Stent, especially in terms of stent thrombosis. The company also announced plans to create a global awareness campaign to educate physicians and patients about guidelines from leading patient and professional medical societies about anti-platelet therapy. These guidelines, which are endorsed by the American Heart Association (AHA), the American College of Cardiology (ACC) and the Society for Cardiology Angiography and Intervention (SCAI), suggest physicians consider a one-year duration of anti-platelet therapy in patients receiving drug-eluting stents. Clinical Data Presented at the FDA Panel Meeting. The independent, intent-to-treat analysis presented by the Harvard Clinical Research Institute, which applied a new, broad consensus definitions developed by academic investigators, industry and regulators known as the Academic Research Consortium (ARC), demonstrated that the rate of any thrombosis from zero-four years was 3.5 percent (29 patients from a pool of 832) for the Cypher Stent arm and 3.4 percent (28 patients from a pool of 825) for bare-metal stents. The analysis was performed on the complete four-year data of 1,748 patients, the longest of any drug-eluting stent, from the randomized clinical trials SIRIUS, E-SIRIUS, C-SIRIUS and RAVEL, all of which compared the Cypher Stent to bare-metal stents in the treatment of de novo coronary artery lesions. The data did demonstrate differences in the timing of the incidence of such events between bare-metal and drug-eluting stents. At no point throughout the four-year period were the differences significant. Analyses of sub-populations are ongoing. The ARC definitions for thrombosis included definite, which required confirmation of stent thrombosis by angiogram at follow up; probable, which included a MI in the treated vessel in patients who did not have an angiographic confirmation of a thrombosis; and possible, which included sudden unexplained death that could not be attributed to another cause, such as a car accident or cancer. These definitions were used to capture all possible adverse events that might be attributable to stent thrombosis and to thoroughly evaluate the long-term safety of potential treatments for coronary artery disease. Thrombosis that was considered definite or probable, a more specific assessment of the rates of thrombosis in the two treatment arms according to the ARC definitions, was 1.6 percent (13 out of 832 patients) in the Cypher Stent group and 1.7 percent (15 out of 870 patients) in the bare-stent arm from zero-four years. The ARC group, led by Professor Patrick Serruys, MD, The Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands, and Dr. Donald Cutlip, created the standardized definitions to facilitate uniform assessment of data for drug-eluting stents. The Consortium represented participants in the Scientific Working Sessions on Study Endpoints in PCI Trials earlier this year in Washington and Dublin, including HCRI, the Cardiovascular Research Foundation and Duke Clinical Research Institute from academia; the FDA, several academic medical centers and hospitals, and, from industry, Abbott Vascular, Boston Scientific, Cordis Corporation, Conor Medsystems and Medtronic. Joint Commission Seeks Input on National Patient Safety Goals The Joint Commission on Accreditation of Healthcare Organizations released for review a list of DRAFT Goals and Requirements that will be considered for potential inclusion in the 2008 National Patient Safety Goals. The National Patient Safety Goals, which are updated annually, are designed to require health care organizations to protect patients from the negative impact of specific health care errors. The draft Goals include requiring organizations to: Improve recognition and response to changes in a patient's condition Reduce the risk of post-operative complications for patients with obstructive sleep apnea Prevent patient harm associated with health care worker fatigue Prevent catheter misconnections Potential Requirements for review also include requiring organizations to investigate and initiate planning for the use of technology to assist with patient identification, and to reduce the likelihood of patient harm associated with the use of anticoagulation therapy. The full text of the potential Goals on the list are posted on the Joint Commission website, www.jointcommission.org, and has been distributed for comment to health care professionals, providers, consumers and other stakeholders. The deadline for feedback is Thursday, January 26, 2007. The list of potential Goals and Recommendations has been developed by a panel of well-known patient safety experts, including nurses, physicians, risk managers, pharmacists, and other professionals who have hands-on experience in addressing patient safety issues in a variety of health care settings. Each year, this Sentinel Event Advisory Group reviews the current Goals and Requirements and makes specific recommendations for any changes. The field review offers the opportunity for others to share their judgment about the relevance, priority, clarity, ability to measure compliance, time needed to implement and cost of implementation of each potential Goal and Requirement under consideration. For more information about the field review, please contact Jennifer Hoppe, senior research associate, Division of Standards and Survey Methods, Joint Commission, at 630.792.5936 or jhoppe@jcaho.org. New Harmony® Medical Storage and Procedure Carts InnerSpace's line of Harmony medical storage and procedure carts come in four frame sizes or models and are accommodate a range of storage needs. All four models are available with standard drawer configurations or can be customized using the Build-A-Cart option. Heavy-duty plate casters, central key-lock and a pull-out writing surface are standard on every Harmony. An optional electronic keyless entry is also available that incorporates an auto re-lock feature, low battery indicator and manual key override. Anesthesia and Crash carts come standard with a tracking caster, making the carts easy to maneuver when pushing over long distances. The Build-A-Cart option allows for custom configurations using 3, 6 and 9 drawers or 3, 6 and 9 trays and baskets. A locking drawer can be used in conjunction with trays and baskets to comply with JCAHO standards for medications and syringes. A full compliment of accessories is available to accommodate medical equipment and devices, monitors, laptop computers and other items that increase the cart's functionality. Harmony's slotted aluminum frame rails are designed for easy installation and positioning of side-mounted accessories. All Harmony models are available in white and Harmony 24 models are also available in blue, yellow and red. InnerSpace Corporation offers storage and inventory solutions for the healthcare industry. For more information, visit www.innerspacecorp.com. Medtronic Presents Data on Next Generation Endeavor® Drug-Eluting Stent at Special FDA Panel Meeting on DES Safety Medtronic, Inc. presented safety and efficacy data from the company's extensive Endeavor® drug-eluting stent clinical trial program at a special U.S. Food and Drug Administration advisory panel meeting convened to discuss growing concerns about drug-eluting stent safety. Specifically, the data demonstrates a significant reduction in the need for repeat procedures compared to bare metal stent controls, and a low rate of stent thrombosis in approximately 1,300 patients followed for two to three years in Endeavor clinical trials. The Endeavor drug-eluting stent system is an investigational device and not yet approved in the United States. Medtronic submitted its Endeavor Pre-Market Approval (PMA) application on Nov. 16 and anticipates U.S. approval in 2007. The PMA includes safety and efficacy data on approximately 4,100 patients who have been treated with the Endeavor stent. The PMA also reflects data from the largest, most wide-ranging patient population and for patients with the longest follow up ever submitted to support approval of a new drug-eluting stent. Medtronic Sr. Vice President, Richard E. Kuntz, MD is the co-founder of the Harvard Clinical Research Institute (HCRI), where as Chief Scientific Officer, he helped direct more than 100 multi-center clinical trials involving approximately 45,000 patients, including most of the major drug-eluting stent trials for DES manufacturers. At the FDA meeting, Dr. Kuntz provided data regarding the safety of the Endeavor stent using multiple definitions of stent thrombosis. According to the pre-specified clinical trial protocol definitions, the Endeavor stent has an overall thrombosis rate of 0.3 percent, with no stent thrombosis beyond 30 days. Using the broader, proposed stent thrombosis definitions recently created by the independent Academic Research Consortium, Endeavor showed a similarly low stent thrombosis rate of 0.5 percent.

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