Cordis Corporation, a Johnson & Johnson company, is a worldwide leader in the development and manufacture of interventional vascular technology. Through the company’s innovation and research and development, Cordis partners work with interventional cardiologists worldwide to treat millions of patients who suffer from vascular disease. More information about Cordis Corporation can be found at www.cordis.com.
Largest Study to Date Finds Drug-eluting Stents and Bare-metal Stents Yielded Similarly Low Mortality Rates
Warren, New Jersey – 13 September 2007 – A network meta-analysis of 38 randomised controlled trials encompassing more than 18,000 patients found that the mortality risks associated with drug-eluting stents and bare-metal stents are similarly low. This analysis, the largest of its kind to date, comparing drug-eluting stents – the Cypher® Sirolimus-eluting Coronary Stent and the Taxus Stent – with bare-metal stents, appears this week in the medical journal ‘The Lancet’.
The analysis also found a substantial reduction in the risk of myocardial infarction (heart attack) and re-intervention with the Cypher Stent compared with bare-metal stents and the Taxus Stent, and no significant differences in the rates of stent thrombosis (blood clots) between the Cypher Stent and bare-metal stents. The data from this analysis also identified a significant decrease in the risk of blood clots occurring more than 30 days after stent implantation with the Cypher Stent compared with the Taxus Stent.
“This large set of data indicates that the mortality associated with drug-eluting stents and bare-metal stents is comparable. Recent concerns about increases in mortality associated with drug-eluting stents are not supported by this analysis when assessing long-term outcomes,” stated Dr Christoph Stettler, Medical Director (MD), from the University of Bern, Switzerland. Dr Stettler is with the Department of Endocrinology, Diabetes and Clinical Nutrition.
In addition, the corresponding author, Dr Peter Juni, MD, stated that, ‘These results have also led us to conclude that the Cypher Stent is clinically superior to bare-metal stents and the Taxus Stent when the safety and effectiveness outcomes in this analysis are taken into account.’ Dr Juni is Head of Division, Clinical Epidemiology and Biostatistics, University of Bern, in Switzerland.
Funded by the Swiss National Science Foundation, the network meta-analysis was designed to compare the safety and effectiveness of bare-metal stents – the Cypher Stent and the Taxus Stent – in a large patient population to increase the ability to detect and understand low-frequency events, such as death and stent thrombosis. It included data of up to four years of follow-up. The safety outcomes comprised mortality (death), myocardial infarction and Academic Research Consortium (ARC) definite stent thrombosis. The effectiveness outcome was target lesion re-vascularisation (or the need for a repeat intervention).
The mortality rates were similar for all three stents: hazard ratios (HR) were 1.00 (95% confidence interval (CI) 0.82–1.25) for the Cypher Stent versus bare-metal stents, 1.03 (CI 0.84–1.22) for the Taxus Stent versus bare-metal stents and 0.96 (CI 0.83–1.24) for the Cypher Stent versus the Taxus Stent.
The Cypher Stent was associated with the lowest risk of myocardial infarction. The corresponding HR’s were 0.81 versus bare-metal stents (CI 0.66–0.97, p=0.030) and 0.83 versus the Taxus Stent (CI 0.71–1.00, p=0.045).
The ARC definite stent thrombosis rates between the Cypher Stent and bare metal stents were not significantly different over the entire follow-up. However, the risk of late stent thrombosis (occurring more than 30 days after the procedure) was more than twice as likely with the Taxus Stent compared with bare-metal stents (HR 2.11, CI 1.19–4.23, p=0.017). In addition, the study found that a late stent thrombosis event was 46% less likely to occur in a patient implanted with the Cypher Stent than in a patient who received the Taxus Stent (HR 0.54, CI 0.26–0.98, p=0.041).
While both drug-eluting stents were associated with significantly lower risks of target lesion re-vascularisation compared with bare-metal stents, the Cypher Stent reduced the risk substantially further compared with the Taxus Stent. The Cypher Stent reduced the risk by 70% (HR 0.30, CI 0.24–0.37, p=0.0001) and the Taxus Stent by 58% (HR 0.42, CI 0.33–0.53, p=0.0001) compared with bare-metal stents. When the target lesion re-vascularisation rate for the Cypher Stent was compared directly with the rate for the Taxus Stent, a patient implanted with the Cypher Stent was found to be 30% less likely to need another procedure than a patient treated with the Taxus Stent (HR 0.70, CI 0.56–0.84, p=0.0021). This difference is consistent with other meta-analyses of randomised controlled trials directly comparing the two stents.
“This network meta-analysis constitutes the largest and most robust set of data published to date in an eminent international peer-reviewed journal assessing the long-term safety and efficacy outcomes of drug-eluting stents,” said David E Kandzari, MD, Fellow of the American College of Cardiology (FACC), Fellow of the Society for Cardiovascular Angiography and Interventions (FSCAI), Chief Medical Officer, Cordis Corporation.” It significantly enriches the large body of evidence that interventional cardiologists have at their disposal to make the right choice for their patients. These data clearly demonstrates the benefits of drug-eluting stents versus bare metal stents and further provide clarity as to the differences between the Cypher Stent and the Taxus Stent.”
About the Cypher Stent
The Cypher Stent has been chosen by cardiologists worldwide to treat approximately three million patients with coronary artery disease. The safety and efficacy of the device is supported by a robust clinical trial programme that includes more than 70 studies that examine the performance of the Cypher Stent in a broad range of patients.
Developed and manufactured by Cordis Corporation, the Cypher Stent is currently available in more than 80 countries and has the broadest clinical experience and longest-term clinical follow-up of any drug-eluting stent. The next version of sirolimus-eluting stent, the Cypher SelectTM Sirolimus-eluting Coronary Stent, was launched in Europe, Asia Pacific, Latin America and Canada in 2003. The Cypher Select Plus Stent, the third version of a sirolimus-eluting coronary stent, received CE Mark in 2006 and is currently available in many markets outside the US.
For more complete information on indications, contraindications, warnings and precautions, see the Instructions for Use available at www.cypherstent.com.
Largest Study To Date Shows Significant Reductions in Risks of Blood Clots and Reintervention with Cypher® Sirolimuseluting Coronary Stent Compared with Taxus Stent
Miami Lakes, Florida – 4 September 2007 – In an extensive analysis of clinical trials known as a meta-analysis, the Cypher Sirolimus-eluting Coronary Stent was associated with significantly lower risks of blood clots and the need for re-intervention, compared to the Taxus Stent out to 30 months after an angioplasty procedure. This meta-analysis of 16 randomised clinical trials and 8,695 patients, the largest analysis of its kind to date, is now posted on the Journal of the American College of Cardiology website and is expected in print later in the year.
“Over the past year, concerns have been raised regarding the long-term safety of all drug-eluting stents,” said Professor Albert Schömig, MD, from Deutsches Herzzentrum, Technische Universität in Munich, Germany. “In this meta-analysis of randomised controlled trials, the Cypher Stent was associated with a significant reduction in the risks of stent thrombosis and re-intervention, compared with the Taxus Stent. This reinforces the notion that there are marked differences between the Cypher Stent and the Taxus Stent and that the safety of these drug-eluting stents must be assessed separately.”
Professor Schömig added, “We find these data compelling because they are consistent with other documented meta-analyses and reflect data from all of the randomised clinical trials directly comparing these drug-eluting stents. Meta-analyses like these are an important and well-accepted statistical method among clinicians worldwide for documenting similarities and differences between two treatment modalities. We understand and appreciate that such studies are open to various interpretations by researchers and clinicians.”
The primary safety end-point of the meta-analysis was protocol-defined stent thrombosis, while the secondary safety end-points were death and heart attack (myocardial infarction, MI). The primary efficacy end-point was the need for re-intervention (target lesion revacularisation, TLR).
According to this comprehensive analysis of all head-to-head clinical studies between the Cypher Stent and the Taxus Stent, a blood clot (stent thrombosis) is 34% less likely to form in patients implanted with the Cypher Stent than in patients who receive the Taxus Stent – a statistically significant difference (HR 0.66, 95% CI 0.46–0.94, p=0.02). In addition, the Cypher Stent significantly lowered the risk of reintervention by 26% versus the Taxus Stent (HR 0.74, CI 0.63–0.87, p<0.001).
While the overall risk of death was not significantly different between the two drug-eluting stents (HR 0.92, CI 0.74–1.13, p=0.43), the authors of the meta-analysis identified a trend towards a lower risk of heart attack with the Cypher Stent versus the Taxus Stent (HR 0.84, CI 0.69–1.03, p=0.10), especially after the first year of follow-up.
Events occurring after the first year of stent placement have fuelled the discussion surrounding the safety of drug-eluting stents. When only patient-level data were used, the authors were able to assess the occurrence of events after the first year of follow-up. In this analysis, there was a significant 70% reduction in blood clots (p=0.004) and a 55% reduction in repeat heart attacks (p=0.006) in patients who received the Cypher Stent compared with patients implanted with a Taxus Stent.
“This meta-analysis substantially enriches the large body of evidence that interventional cardiologists have at their disposal to make the right choice for their patients,” said David E Kandzari, MD, FACC, FSCAI, Chief Medical Officer, Cordis Corporation. “Drug-eluting stents, like the Cypher Stent, continue to provide significant benefits for patients with coronary artery disease.”
For this analysis of randomised controlled trials, the gold standard of clinical evidence in medicine, individual patient data were obtained from 11 of the 16 included studies or 5,562 patients. The authors noted in the manuscript that the overall treatment effects were similar regardless of how the data were analysed – total patient population or analysis of individual patient data.
The meta-analysis comprised studies of simple cases, studies that included all types of patients and studies that focused on specific and complex patient populations, such as patients with diabetes, patients treated for disease in long lesions or small vessels, patients presenting with a heart attack and patients being treated for repeat disease in a previously placed bare-metal stent, some of which are not within the approved labelling for the products.
Cordis Corporation has entered into an exclusive worldwide licence with Wyeth for the localised 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 Pharmaceuticals, a division of Wyeth, under the name Rapamune®. Rapamune is a trademark of Wyeth Pharmaceuticals.