CME/CEU Activity: Sirolimus-Eluting Stents: Evolving New Standards in Coronary Artery Disease

PLEASE DOWNLOAD THE PDF FOR QUESTIONS AND OBJECTIVES, WHICH MUST BE SUBMITTED IN ORDER TO OBTAIN CREDIT. Topics: Sirolimus-Eluting Stents: Evolving New Standards in Coronary Artery Disease Faculty/Credentials: Alexander Abizaid, MD, Consultant Interventional Cardiologist, Director, Catheterisation Laboratory, Institute Dante Pazzanese of Cardiology, Av Dr. DANTE Pazzanese 500, Ibirapuera, Sao Paulo, Brazil, 04012-180 Brazil Learning Objectives. On completion of this activity, participants will have increased skills in: 1. Evaluating new drug-eluting stent technologies; 2. Interpreting drug-eluting stent clinical trial results; 3. Understanding the importance of late loss, target lesion revascularisation and angiographic binary restenosis rates as predictors of long-term outcomes following treatment with a drug-eluting stent; 4. Identifying the three main predictors of restenosis. Activity instructions. Successful completion of this activity entails reading the article, answering the test questions and obtaining a score of over 70%, and submitting the test and completed evaluation form to the address listed on the form. Tests will be accepted until the expiration date listed below. A certificate of completion will be mailed to you within 60 days. Estimated time to complete this activity: 1 hour Initial release date: September 30, 2003 Expiration date: September 30, 2004. Target audience. This educational activity is designed for physicians, nurses and cardiology technologists who treat patients with coronary artery disease. Accreditation statements. This activity is sponsored by HMP Communications. Physicians: HMP Communications is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. HMP Communications designates this continuing medical education activity for a maximum of 1 category 1 credit toward the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/she actually spent in the educational activity. This activity has been planned and produced in accordance with the ACCME Essential Areas and Policies. Nurses: Provider approved by the California Board of Registered Nursing, Provider Number 13255 for 1 contact hour. Radiologic Technologists: Activities approved by the American Medical Association (AMA Category 1) are eligible for ARRT Category B credit as long as they are relevant to the radiologic sciences. Radiologic Technologists, registered by the ARRT, may claim up to 12 Category B credits per biennium. SICP: Society of Invasive Cardiovascular Professionals (SICP) approved for 1 CEU. Commercial support disclosure. This educational activity has been supported by an educational grant from Cordis Corporation. Faculty disclosure information. All faculty participating in Continuing Education programs presented by HMP Communications are expected to disclose to the meeting audience any real or apparent conflict(s) of interest related to the content of their presentation. Dr. Abizaid discloses that he is a consultant for several companies, including Cordis Corporation, Abbott Vascular and Boston Scientific. Sirolimus-Eluting Stents: Evolving New Standards in Coronary Artery Disease Alexander Abizaid, MD, Consultant Interventional Cardiologist, Director, IVUS Core Laboratory, Institute Dante Pazzanese of Cardiology Sao Paulo, Brazil Unlike 1977, when Andreas Gruntzig performed the first balloon angioplasty, intracoronary stent implantation has become established as the predominant method of percutaneous coronary artery revascularization. This is because of its ease of use and lower frequency of clinical and angiographic restenosis compared with balloon angioplasty. Moreover, improvements in stent technology and operator skills, combined with better use of adjunctive anti-platelet therapy have contributed to the improvement in short- and long-term outcomes of patients treated with percutaneous intervention. Similarly, the difference in outcome as measured by Major Adverse Coronary Events (MACE) between stent implantation and coronary artery bypass graft surgery (CABG) has decreased to almost single digits. This has led experts to predict that with the advent of drug-eluting stents (DES) there will be little or no difference between percutaneous coronary artery intervention (PCI) and CABG in terms of long-term outcome. However, coronary artery disease (CAD) remains one of the major causes of mortality and morbidity among adults and intracoronary stenting is generally considered the most important development in the field of percutaneous coronary revascularisation since the introduction of balloon angioplasty in 1977. While bare metal stents have targeted the underlying issues of elastic recoil and arterial remodeling, angiographic restenosis continues to be the ˜Achilles Heel’ of interventional cardiology, with an estimated 17%-32% of patients requiring repeat treatment. The introduction of drug-eluting stents is helping to transform the practice of intracoronary stenting and to offer hope to those patients considered to be ‘high risk’ such as diabetics, patients with a previously treated with balloon angioplasty or those for whom surgery was previously the only option. This paper discusses the recent advances and lessons learned about the use of the Cypher Sirolimus-eluting coronary stent (SES) in the management of CAD as well as highlighting the importance of the latest clinical evidence from New SIRIUS (the combined results from C- and E-SIRIUS, two of the four major clinical trials from the comprehensive SES international clinical trial program). Introduction Since the presentation of the first-in-man study (FIM study) involving the use of SES in 2000, the level of anticipation for drug-eluting stents has grown beyond expectation. More recently, this interest has been fueled by the most recent, encouraging results from New SIRIUS. Now in its sixth year, the SES clinical trial program is the largest drug-eluting stent database of its kind. Designed and powered to provide healthcare professionals with clear safety and efficacy data, the Cordis strategy, when developing their clinical trial program, evolves through 5 distinct phases. First was the feasibility study (FIM), involving small numbers of patients (10-50). Pivotal studies then followed, mainly for regulatory approval, such as CE mark and FDA approval. These were large-scale, prospective, randomized, multi-center, double-blind controlled trials involving large numbers of patients (RAVEL, SIRIUS, C- and E-SIRIUS) evaluating both safety and efficacy. In addition, the results from trials designed to provide health economic data and support the move to reimbursement will follow (E-& C-SIRIUS, SIRIUS and ARTS II). Further studies designed to evaluate the technology in expanding indications are in varying stages of implementation, initially as feasibility studies and then, dependent upon the outcome of the feasibility studies, larger studies will be undertaken (TROPICAL for in-stent restenosis, FREEDOM and DECODE for diabetes and bifurcation). New SIRUS: A New Benchmark for Comparison In the 17 months since the Cypher Sirolimus-eluting coronary Stent (SES) first became available, we have all come to recognize the valuable lessons learned from ongoing controlled clinical trials and ‘real world’ experience. We are all now more aware of the importance of target lesion revascularisation (TLR) rates and late loss as predictors of long-term outcome with a drug-eluting stent (DES). The results from New SIRIUS clearly show the benefits to be gained from careful operator technique if we are to avoid peri-stent restenosis and attain restenosis rates of 5% or less (as revealed in New SIRIUS). As the SES clinical trial program has evolved, perhaps the most important observation we can make is the remarkable results from New SIRIUS. With a more challenging patient population than the earlier controlled trials of RAVEL and SIRIUS, New SIRIUS, with smaller post-procedure minimum lumen diameter (MLD) and longer stented lengths, reveals consistent TLR (4.0%) and late loss (0.18mm) results, and superior in-lesion binary restenosis rate. A detailed analysis of the results from New SIRIUS and SIRIUS showed that the major difference between the two trials is the in-lesion binary restenosis, 5.1% vs. 8.9%. Further analysis shows that the difference in in-lesion restenosis rate is primarily due to the difference in the restenosis at the proximal edge. The results are as follows: This compelling finding can be attributed to the different technique employed in New SIRIUS, primarily the use of shorter post-dilatation balloons and direct stenting of 27% of the patients. More importantly, New SIRIUS has clearly established the new standard in randomized clinical trials against which all other DES will be measured. At a time when many interventional cardiologists continue to use angiographic binary restenosis, as well as late loss and TLR, as key comparators between individual DES trials, every percentage point of restenosis counts towards the eventual long-term outcome of our patients. Maximizing Clinical Outcome with SES The following represents a summary of the key lessons we have learned when implanting a SES in the past three years. First, all efforts should be taken to make sure that the stent is not under-dilated. The internal stent diameter should match the size of the reference vessel diameter. In the RAVEL and SIRIUS trials, the average deployment pressure used was approximately 14 atm. Second, if full contact with the vessel wall is not achieved, a larger post-dilatation balloon may be used to expand the stent further. Post-dilatation occurred in 54% of cases to achieve true stent apposition in the SIRIUS trial. Post-dilatation balloons should be shorter than the stent length, and again centered within the stented area to prevent injury outside of the stent edges. The use of a balloon shorter than the stent and without a hydrophilic coating may minimize balloon movement during inflation, minimizing injury outside the stented area. It is important not to exceed the expansion limits of the Cypher Stent, e.g., 3.75mm for a 6-cell Cypher Stent (2.5 & 3.0mm) and 4.75mm for a 7-cell (3.5 and 4.0mm). Third, when overlapping two Cypher Stents, it is obviously crucial not to leave a gap. Pre-dilatation balloons should be shorter than the intended stent length, and centered within the intended stent area. Care should be taken to note exactly where pre-dilatation occurs in order to cover any injured areas with the stent. Foreshortening of the Cypher Stent varies from 0.3- 1.0 mm, depending on stent length and diameter. Based on clinical experience, several physicians have recommended a 3-4mm overlap to avoid geographic miss. To ensure there is no gap following deployment of a second stent, the distal balloon marker of the second stent should be inside the first deployed stent. Four, experience from clinical trials has reinforced the need for careful operator technique to maximize the potential benefit of Cypher Stent implantation. Stent and balloon selection, deployment technique and adjunctive drug regimens may all be critical to success. Five, to adequately cover the reference segment disease it is recommended that clinicians first choose the stent length based on the diseased area to be treated. Use of IVUS and a marker wire may optimize stent length selection. It is important to stent disease-free to disease-free normal reference vessel areas, by choosing a safe landing zone outside the shoulders of the lesion. This will reduce exposed areas that may be prone to disease progression. If after measuring a lesion the stent length is still in question, it is preferable to choose a longer stent. Six, concerning adjunctive drug regimens, it is recommended that current GP IIb/IIIa practice is maintained, with consideration for the lesion and patient type to be treated. Anti-platelet therapy is obligatory, although the length of treatment may vary. In RAVEL, 2 months APT was used, whereas in the real-world patient cohort of SIRIUS, clopidogrel/ticlopidine was prescribed for 3 months, and in New SIRIUS for 2 months. For off-label use such as saphenous graft lesions, multi-vessel disease, in-stent restenosis, specially after brachytherapy failure, at least 6-month use of clopidogrel is recommended. Conclusion The superior results obtained in the more challenging patient population in New SIRIUS supports the concept that refinement in deployment techniques may further improve clinical outcomes. Moreover, the key lessons learned from New SIRIUS are: Use longer stents (normal vessel to normal vessel); Optimize stent expansion (i.e., match stent diameter to reference vessel diameter (RVD) as close as possible); If the deployed stent size is still inadequate with respect to vessel diameter or, if full contact with the vessel wall is not achieved, a larger post-dilation balloon may be used to further expand the stent; Use shorter balloons to pre- and post-dilate; When pre-dilating, make sure to cover any injured areas with a stent; Be careful not to post-dilate outside the stent edges; 3-4 mm overlap is recommended to avoid geographic miss; Direct stenting with SES appears to be safe and feasible. In summary, the somewhat superior results of New SIRIUS suggest a growing understanding of how to maximize clinical outcomes with the SES, and suggest that a binary restenosis rate of less than 6% will be the standard by which all other drug-eluting stents will be measured.

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