WASHINGTON, Oct. 24 /PRNewswire/ -- In order to further advance understanding of stent thrombosis, Cordis announced today a study of the multiple factors that may lead to the condition and potential benefits of medical regimens. The 30,000 patient registry, currently underway in Europe and Asia/Pacific, will now extend to the U.S. and will include a prospective randomized subset of patients. This expanded registry will evaluate a variety of safety and efficacy measures, including the need for repeat procedures (target lesion revascularization), major adverse cardiac events such as heart attack and death, in-stent blood clots (stent thrombosis), as well as detailed information about the use of dual anti-platelet therapy.
Additionally, the company announced that it would extend out 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(R) Stent, especially in terms of stent thrombosis, a rare but serious clinical event.
Cordis also announced that although an independent clinical research organization has confirmed that the safety and clinical benefits of the CYPHER(R) Stent, based on data from four randomized controlled clinical trials, extend out to four years with no significant difference in the incidence of thrombosis (blood clots) between the CYPHER(R) Stent and bare- metal stents, its studies will attempt to understand phenomena related to timing of the events. Data are being presented for the first time at the Transcatheter Cardiovascular Therapeutics (TCT) Conference on Tuesday at the Hotline Session to be held from 12:45 p.m. to 1:45 p.m. (EDT).
Dennis Donohoe, M.D., Vice President, Worldwide Clinical and Regulatory Affairs, Cordis Corporation, said, “We know that thrombosis can and do occur with interventional cardiovascular procedures. Although the incidence of thrombosis is rare, it is of concern and it is an important clinical challenge. We will continue to investigate contributing factors and methods to reduce this risk.”
The independent, intent-to-treat analysis, 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 0-4 years was 3.5 percent (29 patients from a pool of 832) for the CYPHER(R) 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(R) 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 a clot by angiogram at follow up; probable, which included a heart attack 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(R) Stent group and 1.7 percent (15 out of 870 patients) in the bare-stent arm from 0-4 years.
“Our analysis shows that the CYPHER(R) Stent is not associated with an increased overall risk of thrombosis, also known as blood clots, when compared to the same bare-metal stents out to four years,” said Donald Cutlip, M.D., Executive Director and Chief Medical Officer, Harvard Clinical Research Institute (HCRI), Cambridge, Mass., which conducted the independent analysis based on the new ARC definitions. Dr. Cutlip is also Associate Professor of Medicine, Harvard Medical School and an interventional cardiologist at Beth Israel Deaconess Medical Center in Boston.
“The independent analysis by HCRI per the ARC definitions evaluated the data using two definitions of thrombosis -- any and definite/probable thrombosis -- and there is no difference versus bare-metal stents in the rate of thromboses at four years by either version of this standardized definition,” said Dr. Donohoe. “We recognize that data are subject to interpretation by a number of methodologies, some of which may yield significant differences at certain time points, but we are confident that the complete analyses conducted by HCRI provide the most appropriate information about the safety of the CYPHER(R) Stent.”
The HCRI analysis of data based on the ARC definitions is also the first- ever comprehensive evaluation of thrombosis in bare-metal stents out to four years. Dr. Cutlip noted that, “Our study also shows an early hazard for stent thrombosis among the bare-metal stent patients,” Dr. Cutlip said.
“Additional analyses are needed to evaluate the possible association with restenosis and subsequent revascularization procedures. This phenomenon may have been missed by previous studies, which excluded patients with repeat revascularization procedures who sustained later thrombosis events.”
The ARC group, led by Professor Patrick Serruys, M.D., The Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands and Dr. Cutlip, created the standardized definitions to ensure that safety data for drug-eluting stents were comparable. 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.
“The definitions developed by ARC are important because they seek to standardize how we view an event like thrombosis across all clinical studies,” said Dr. Serruys. “Without a common language, ambiguity arises and that is not helpful for physicians or the patients they treat. With these standardized definitions, we succeed in creating a foundation for clinical advancement of interventional cardiology.”
Cordis has been a strong advocate of industry-wide independent adjudication of all clinical trial data using standardized definitions, believing that it is vital to an understanding of the safety of drug-eluting stents. The FDA has requested that Cordis review the readjudicated data based on the ARC definitions at the upcoming panel meeting (December 7-8, 2006).
About the CYPHER(R) Stent
More than two million worldwide patients with coronary artery disease have been treated with the CYPHER(R) Stent. The safety and efficacy of the device is supported by a robust clinical trial program that includes more than 70 studies, inclusive of independent clinical trials, that examine the performance of the CYPHER(R) Stent in a broad range of patients.
Developed and manufactured by Cordis Corporation, the CYPHER(R) Stent is currently available in more than 80 countries and has the longest-term clinical follow-up of any drug-eluting stent. The first next-generation drug- eluting stent, the CYPHER SELECT(TM) Sirolimus-eluting Coronary Stent, was launched in Europe, Asia Pacific, Latin America and Canada in 2003. The CYPHER SELECT(TM) Plus Sirolimus-eluting Coronary Stent, the first third-generation drug-eluting stent, received the CE mark in June 2006 and is now available in many markets outside the United States.
About Cordis Corporation
Cordis Corporation, a Johnson & Johnson company, is a worldwide leader in developing and manufacturing interventional vascular technology. Through the company’s innovation, research and development, physicians worldwide are better able to treat the millions of patients who suffer from vascular disease.
* Cordis Corporation has entered into an exclusive worldwide license with Wyeth for the localized delivery of sirolimus in certain fields of use, including delivery via vascular stenting. Sirolimus, the active drug released for the stent, is marketed by Wyeth.
Cordis Corporation
CONTACT: Christopher Allman, of Cordis Cardiology, (O) +1-786-313-2303,(M) +1-305-586-6024, Callman1@crdus.jnj.com; or Todd Ringler, of Edelman,+1-617-872-1235, Todd.ringler@edelman.com
Web site: http://www.cordis.com/
