CME Offering: The Impact of Sirolimus-Eluting Stents on Patients at High Risk for Restenosis with Bare Metal Stenting

Author(s): 

Atul Sharma, MD and S.Chiu Wong, MD, Maurice R. and Corinne P. Greenberg Division of Cardiology
Department of Medicine, The New York Presbyterian Hospital-Weill Cornell Medical College, New York, New York

This presentation contains discussion of published and/or investigational uses of agents that are not indicated by the FDA. Neither the North American Center for Continuing Medical Education nor Cordis Corporation recommends the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings.

Topics: The Impact of Sirolimus-Eluting Stents on Patients at High Risk for Restenosis with Bare Metal Stenting

Faculty/Credentials: Atul Sharma, MD and S.Chiu Wong, MD, Maurice R. and Corinne P. Greenberg, Division of Cardiology, Department of Medicine, The New York Presbyterian Hospital-Weill Cornell Medical College, New York, New York

Learning Objectives. On completion of this activity, participants will be able to: 1. Identify the subgroups of patients at increased risk for in-stent restenosis with bare metal stents; 2. Describe the major trials demonstrating improved efficacy in treating these high risk populations with sirolimus-eluting stents.

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: June 31, 2004
Expiration date: June 31, 2005.

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 the North American Center for Continuing Medical Education (NACCME).

Physicians: The North American Center for Continuing Medical Education is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American Medical Association has determined that non-US licensed physicians who participate in this CME activity are eligible for AMA PRA category1 credit.

The North American Center for Continuing Medical Education 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: The North American Center for Continuing Medical Education is an approved provider of continuing nursing education by the Pennsylvania State Nurses Association, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation. This continuing nursing education activity was approved for 1 contact hour(s).

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 the North American Center for Continuing Medical Education are expected to disclose to the meeting audience any real or apparent conflict(s) of interest related to the content of their presentation.

Dr. Sharma has nothing to disclose. Dr. Wong discloses he is a consultant and advisory board member for Cordis Corporation, a Johnson & Johnson company.


In 1964, Dotter and Judkins proposed the concept of implanting intravascular stents to support the arterial wall following coronary angioplasty.1 Since that time, predictable angiographic results, improved safety, and proven reductions in target lesion revascularization compared with balloon angioplasty have led to explosive growth in the field of percutaneous coronary stenting. In 1994, less than 1% of the 270,000 angioplasty procedures performed in the US utilized stents.2 Since its approval in 1995 by the FDA for elective procedures, the use of stents has increased dramatically. Coronary stenting provides a mechanical solution to control coronary dissections, prevent acute elastic recoil, and reduce restenosis by routinely increasing target-lesion lumens.3 Initial results of randomized controlled trials demonstrated 25 to 30% reductions in binary restenosis compared with balloon angioplasty.4-5 Subsequent improvements in stent design, flexibility, and deliverability have led to a further decrease in restenosis rates as low as 20% in some studies.6 However, the success of coronary stenting has led to its widespread application in more challenging coronary lesions, and with that, a resultant rise in restenosis rates. Sirolimus-eluting stents (SES) were developed to combat the process of neointimal hyperplasia that ultimately leads to in-stent restenosis, and data from multiple trials have demonstrated large, marked reductions in the rates of target vessel revascularization and angiographic binary restenosis. This review focuses on the impact of sirolimus-eluting stent placement in patients and lesions with traditionally high rates of restenosis with bare metal stenting: patients with diabetes mellitus, small coronary vessels, and long lesions.

Diabetic Patients

Diabetes mellitus has been shown to be an important risk factor for poor outcomes following percutaneous transluminal coronary angioplasty.7 Coronary stents have attenuated both the risk of acute vessel closure and of restenosis compared to balloon angioplasty8 however, the presence of diabetes remains a strong independent risk factor for in-stent restenosis.9 A retrospective observational study by Elezi and colleagues, comparing 715 diabetic patients with 2839 nondiabetic patients, demonstrated increased rates of restenosis (diabetics 37.5% versus nondiabetics 28.3%, p<0.001) and higher rates of death, myocardial infarction (MI), or target vessel revascularization (TVR) at 30 days (diabetics 6.7% versus nondiabetics 3.8%, p<0.0001).10 A greater degree of neointimal hyperplasia is thought to be the mechanism behind the increased restenosis rates, as evidenced by increased late loss and smaller minimum luminal diameter documented on angiographic and intravascular ultrasound follow-up.11 The routine use of abciximab in diabetic patients undergoing percutaneous coronary revascularization with a stent in the EPISTENT trial resulted in a greater than 50% reduction in the need for TVR compared with patients receiving a stent without abciximab (6-month TVR rate of 16.6% in the stent-placebo group versus 8.1% in the stent-abciximab group).12 However, restenosis rates have remained high in other studies involving glycoprotein IIb/IIIa inhibitors and patients with diabetes.13 In a recent trial of 11,500 patients, angiographic restenosis was seen in approximately 33% of all patients treated with bare-metal stents.14 Given that SES aggressively inhibits neointimal hyperplasia,15 there is great optimism that these devices will dramatically impact the rate of restenosis in this high-risk patient subgroup.

The RAVEL (Randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization) trial, published in June of 2002, was a double-blind, placebo-controlled trial comparing the two types of stents for revascularization of single, primary lesions in native coronary arteries.16 The study enrolled 238 patients, and the primary end point was in-stent late lumen loss at 6 months. The percentage of in-stent stenosis of the luminal diameter, rare of binary restenosis, and a composite clinical end point of death, MI, and revascularization (either percutaneous or surgical) was also evaluated. Patients were eligible for the study if they had a single primary lesion 2.5-3.5mm in diameter that could be covered with an 18mm stent. Average lesion length was 9.6mm, with mean vessel size noted as 2.6mm. The SES treatment group demonstrated essentially no late-lumen loss (-0.01±0.33mm) and no episodes of binary restenosis at 6 months. In comparison, the standard-stent group had a late-lumen loss of 0.80±0.53mm and 26.6% restenosis both highly significant reductions. One-year MACE rates were 5.8% in the SES group compared to 28.8% in the bare-metal stent group (p<0.0001), with the difference in events was almost entirely due to a higher TVR rate in the standard-stent group. A sub-group analysis of the 44 diabetic patients in this study, 19 of whom received SES and 25 of whom received bare-metal stents, was recently published.17 In this study, 6 month in-stent late-lumen loss was low for diabetic patients treated with SES, (0.07±0.2mm) in comparison to the bare-metal stent group (0.82±0.5mm, p<0.001), and similar to non-diabetic patients treated with SES (-0.03±0.27mm). There were no episodes of binary restenosis in the diabetic subgroup receiving SES, compared to 42% in diabetics receiving standard stents. Twelve-month clinical MACE rates also favored diabetics receiving SES (90% event-free survival in the SES cohort compared with 52% in the bare-metal group, p<0.01), with the large difference in repeat TVR (0% for SES versus 36% for standard-stent groups, p=0.007) driving the results.

The SIRIUS (Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery) study followed RAVEL and was a larger, (1058 patient) randomized, double-blind trial. SIRIUS again compared SES to bare-metal stents in single, de novo lesions in native coronary arteries.18 In comparison to RAVEL, patients in SIRIUS were:

Older (mean age 62.3 in SIRIUS versus 60.7 in RAVEL, p=0.04),

More likely to have had prior revascularization (24.7% previous CABG, 9.5% previous PCI in SIRIUS compared to 18.1% and 1.7% in RAVEL, p<0.001),

Diabetes mellitus (26.4% versus 18.5%, p=0.10),

Hyperlipidemia and hypertension (73.6% and 67.7% respectively for patients in SIRIUS in comparison to 51.5% and 49.2% respectively for patients in RAVEL, p<0.001).

Patients enrolled in SIRIUS also had more frequent multivessel coronary disease (41.6% versus 29.6%, p<0.001)

and had longer lesions (14.4mm compared with 9.6mm, p<0.001), therefore representing a patient population with more complex coronary disease.

References: 

1. Dotter CT, Judkins MR. Transluminal treatment of arteriosclerotic obstructions. Circ. 1964;30:654.

2. Heart Disease and Stroke Statistics. American Heart Association, Dallas, Texas.

3. Kuntz RE, Gibson CM, Noboyoshi M et al. Generalized model of restenosis after conventional balloon angioplasty, stenting, and directional atherectomy. J Am Coll Cardiol. 1993;21:15-25.

4. Fischman DL, Leon MB, Baim D et al, for the STRESS Trial Investigators. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med. 1994;331:496-501.

5. Serruys PW, de Jaegere P, Kiemeneij F et al, for the Benestent Study Group. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med. 1994.331:489-495.

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7. Stein B, Weintraub WS, Gebhart SP et al. Influence of diabetes mellitus on early and late ouctome after percutaneous transluminal coronary angioplasty. Circ. 1995;91:979-989.

8. Van Belle E, Perle M, Braune D et al. Effects of coronary stenting on vessel patency and long-term clinical outcome after percutanueous coronary revascularization in diabetic patients. J Am Coll Cardiol. 2002;40:410-417.

9. Abizaid A, Kornowski R, Mintz GS et al. The influence of diabetes mellitus on acute and late clinical outcomes following coronary stent implantation. J Am Coll Cardiol. 1998;32:548-549.

10. Elezi S, Kastrati A, Pache J et al. Diabetes mellitus and the clinical and angiographic outcome after coronary stent placement. J Am Coll Cardiol. 1998;32:1866-1873.

11. Marso SP, Mak KH, Topol EJ. Daibetes mellitus: biological determinants of atherosclerosis and restenosis. Semin Interv Cardiol. 1999;4:129-143.

12. Marso SP, Lincoff AM, Ellis SG et al. Optimizing the percutaneous interventional outcomes for patients with diabetes mellitus: results of the EPISTENT (Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial) diabetic substudy. Circ. 1999;100:2477-2484.

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18. Moses JW, Leon MB, Popma JJ et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med. 2003;349:1315-1323.

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20. Lemos PA, Serruys PW, van Domburg RT, et al. Unrestricted utilization of sirolimus-eluting stents compared with conventional bare stent implantation in the real world: the rapamycin-eluting stent evaluated at rotterdam cardiology hospital registry. Circ. 2004;109:190-195.

21. Orlic D, Bonizzoni E, Stankovic G et al. Treatment of multivessel coronary artery disease with sirolimus-eluting stent implantation: immediate and mid-term results. J Am Coll Cardiol. 2004;43:1154-1160.

22. Zaida KM, Kapadia SP, Belli G et al. Prognostic value of absolute versus relative measures of the procedural result after successful coronary stenting: importance of vessel size in predicting long-term freedom from target vessel revascularization. Am Heart J. 2001;141:823-831.

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Anonymoussays: August 7.2010 at 09:55 am

These studies rarely comment on the dependency of plavix or now effient, often for the rest of a patients life.

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