CME/CEU Offering: Small Vessel Stenting
March 2004
Topics: Small Vessel Stenting
Faculty/Credentials: Brian H. Galbut, MD, Gary L. Schaer, MD, FACC, FSCAI
Cardiac Catheterization Laboratories, Rush University Medical Center, Chicago, Illinois
Learning Objectives. On completion of this activity, participants will have increased skills in: 1. Describing the mechanisms of restenosis after PTCA or stenting; 2. Identifying the 3 key patient and lesion characteristics that influence restenosis rates after bare metal stenting; 3. Defining the clinical trials comparing PTCA to stenting in small coronary vessels; 4. Describing recent advances in stent technology that hold promise for future treatment of small vessel disease
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: March 31, 2004
Expiration date: March 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 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: HMP Communications 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 Guidant 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. Galbut has nothing to disclose. Dr. Schaer discloses that he has received a research grant from Cordis Corporation, Guidant Corporation and Medtronic Vascular. Dr. Schaer also discloses that he is a member of the scientific advisory boards for Medtronic Vascular and Abbott Vascular.
To obtain credit, click here to download PDF
The landmark trials BENESTENT1 and STRESS2 clearly demonstrated the advantage of stenting over balloon angioplasty in vessels with a diameter >= 3 mm. Whether stenting is similarly superior to balloon angioplasty in small vessels has been more controversial. The worse outcome of small vessel stenting was clearly demonstrated by Akiyama and coworkers.3 In their retrospective study of 1298 patients enrolled between 3/93 and 5/96, they found that stenting small vessels (mean vessel diameter of 2.64 mm) was associated with a higher restenosis rate (32.6% vs 19.9%, pWhat are Small Vessels and Why are They Unique? The definition of small vessel has varied considerably from one trial to the next. Of the 15 trials of small vessel intervention reviewed for this article (Table), 6 (40%) defined small vessel as any intervened upon segment of coronary artery Is the Vessel Truly as Small as it Looks Angiographically? Intravascular ultrasound (IVUS) has taught us that angiographically determined vessel size can be deceiving. Although a proximal or mid LAD, circumflex or right coronary artery may appear to be Pathophysiology of Restenosis After Stenting Small Vessels Achievement of an immediate increase in vessel lumen diameter (acute gain), without significant renarrowing of the vessel over time (late loss) determines the ultimate clinical success or failure of all coronary interventions. It is not surprising that the extent of acute gain predicts target lesion revascularization rate (TLR). Although stenting confers a clear advantage in acute gain compared with balloon angioplasty, it actually results in more late loss. This is because the metal tines of the deployed stent cause damage to the vessel intima and media, and this stimulates more intimal hyperplasia (scar tissue growing between the tines of the stent) and therefore late loss due to encroachment of the lumen of the vessel. IVUS studies have taught us that all bare metal stents produce a late loss of between 0.8 and 1.0 mm. This tissue encroachment presents a greater problem in small vessels than larger vessels (Figure 2), and therefore more clinically apparent restenosis. For example, if a stent is placed in a 2.0 mm vessel and there is 1.0 mm of late loss at 6 months, the vessel lumen is narrowed 50%. This obstruction may limit adequate oxygen supply to the myocardium with increased demand. In contrast, if a stent is placed in a 3.0 mm vessel and there is 1.0 mm of late loss at 6 months, the vessel lumen is narrowed only 33%. In this case, the lumen is large enough to supply oxygen to the myocardium, even in the case of increased demand. Do Bare Metal Stents Reduce Restenosis in Small Vessels? Although the safety of stenting small vessel disease has been well established, the long-term clinical benefits seen in most of the randomized trials suggest no benefit over balloon angioplasty alone (Table). However, three trials published within the past 3 years have demonstrated benefit of stenting in small vessels.4-6 These recent studies may reflect the evolution of stent technology and deployment techniques. Controversy continues to exist surrounding stenting of more complex small vessel disease, especially in diabetic patients and in those with long lesions. In addition, the clinical trial data have yet to clarify in precisely what vessel size benefits can be expected. In the diabetic population, a study by Suwaidi and co-workers7 is the only trial that focused exclusively on this high-risk subgroup undergoing stenting of small vessel lesions. The study group was small, only 100 patients total, and results indicated no significant improvement with stenting. In a much larger study of 2602 patients, Elezi et al8 compared the outcomes among patients with symptomatic coronary artery disease and varying vessel sizes treated with stenting. These investigators confirmed prior data demonstrating a higher restenosis rate among those stented patients with the smallest vessel diameters. Importantly, they also identified that the concomitant presence of diabetes and long lesions dramatically increased the risk of restenosis after small vessel stenting. Although these data argue against small vessel stenting in higher risk groups such as diabetic patients and long lesions, the advent of drug-eluting stents for small vessels will likely change our current conservative approach (see below). Advances in Stent Design Strategies that limit injury to the vessel wall would seem to play a critical role in developing a stenting technology that would allow realization of the benefit of enhanced early gain without substantial late loss in treating small vessel disease. One such strategy is the development of thin-strutted stents. Although not specifically a trial of small vessels, The ISAR-STEREO-2 trial by Pache and coworkers9 addressed the issue of whether the thin-strutted Multi-Link stent (50 micron strut thickness) conferred any restenosis advantage compared to thick-strutted BX Velocity stent (140 micron strut thickness). In 611 patients randomized between the two interventions, the thin strutted stent was clearly superior with a restenosis rate of 17.9% compared to 31.4% in the thick-strut group (p p=0.002). Theoretically, the benefits of thin struts should be evident in small vessels as well. In vessels with diameters between 2.75 and 3.0 mm, Briguori and co-workers6 (Figure 3) demonstrated significantly less restenosis following stenting with a thin strutted stent (=0.10 mm). However, no significant benefit was observed in vessels 2.51 to 2.75 or in those 5 compared a heparin coated small vessel stent to balloon angioplasty in 145 patients. Mean reference vessel diameter was 2.44 in the stent group and 2.38 mm in the balloon group (p=NS). Event free survival was significantly greater in the stent group 90.5 vs 76.1 in the angioplasty group (p p=0.15). Another trial by Haude and coworkers10 found similar outcomes in small vessels stented with a heparin-coated versus a bare-metal stent. Both stent groups demonstrated improved minimal luminal diameter over balloon angioplasty alone, but there was no difference in major adverse coronary events or restenosis. One potential explanation for the disparity in results between the positive Moer study and the negative Haude study is the fact that the Haude study focused on smaller vessels (2.0 to 2.6 mm), whereas the Moer study included patients with vessel diameters from 2.1 up to 3 mm. This disparity further underscores the challenge of treating vessels 2.6 mm and less. In spite of the above-mentioned apparent dependence on vessel size, a recent non-randomized study by Grenadier and coworkers11 using a phosphorylcholine-coated (PC-coated) stent demonstrated an acceptably low rate of major coronary events at 6 months in stenting vessels less than 2 mm. Phosphorylcholine is a component of the red cell membrane that is believed to decrease the likelihood of in-stent thrombosis. These results underscore the need for stents specifically designed for small vessels. However, randomized trials comparing these very small vessel stents to balloon angioplasty are needed. Garcia and coworkers12 studied the performance of the Pixel stent specifically designed for small vessels. In 350 patients with vessel diameter between 2.2 and 2.7 mm, the benefit of a pre-dilation strategy was compared to a direct stenting approach. Procedural success and 6-month outcomes were remarkably good in both groups, with a low TLR rate of 4.3% in the pre-dilation group and a 3.4% rate in the direct stenting group. There was a non significant trend toward a lower restenosis rate with direct stenting 16% vs 25%. Although not proving superiority of stenting small vessel disease over balloon angioplasty, these data suggest that excellent outcomes can result from using advanced stent technology developed specifically for small vessels. The specific advantage of direct stenting is encouraging but will require further study. Another recent advance in stent technology is the use of new alloys rather than the traditional stainless steel. Both the Guidant Multi-Link Vision stent (Figure 4) and the Medtronic Driver stent are made of proprietary alloys that incorporate cobalt and chromium. The advanced stents confers a number of advantages, including thinner stent struts, preserved visibility and enhanced flexibility. Although registry data for both of these stents have demonstrated excellent performance and clinical outcomes with low TLR rates, there has not yet been any randomized study comparing these stents to balloon angioplasty in vessels Drug-Eluting Stents for Small Vessel Lesions Drug-eluting stents will likely represent the most important technical advance in the management of small vessel disease. These devices work by incorporating an antiproliferative agent (e.g., sirolimus) into a polymer coating the surface of the stent. This permits the drug to gradually release into the vessel wall, thereby inhibiting intimal hyperplasia and the restenosis process. Although not exclusively a small vessel trial, data from the SIRIUS trial by Moses and coworkers13 demonstrated dramatic inhibition of intimal hyperplasia in the DES group compared to the bare metal stent group. Both angiographic restenosis and TLR rates were dramatically reduced for the trial as a whole and for all subgroups. Similar benefits were observed in the TAXUS trial presented by Dr. Gregg Stone at the Transcatheter Therapeutics Meeting in September 2003. The TAXUS trial employed a stent that released another potent antiproliferative agent, paclitaxel. These data also showed a dramatic reduction in restenosis, TLR and late loss compared with the bare metal stent. What is the evidence that drug-eluting stents are effective in small vessels? Although not specifically focused on small vessels, data are available from the cohort of patients receiving DES for vessels 14 randomized 352 patients with a long lesion (15 to 32 mm) in a small coronary artery (2.5 to 3.0 mm diameter) to the sirolimus-eluting Cypher stent or a bare-metal stent. At 8-month angiographic follow-up, minimum lumen diameter was significantly larger with the Cypher stent than with the control stent (2.22 vs 1.33 mm, pp=0.0001). Target lesion revascularization rates were also substantially reduced by the drug-eluting strategy (8.0 vs 22.6%, p=0.0002). These data have important implications for percutaneous revascularization of patients with long lesions in small vessels, a group with an extremely high risk of restenosis and need for repeat revascularization. Conclusions Small vessel disease is currently and will continue to be a challenging area for the interventional cardiologist. We are encouraged by early data from DES trials that demonstrate dramatic reduction in restenosis and clinical events in vessels 2.5 to 3.0 mm. However, it still remains to be proven whether a drug eluting stent will confer benefits over balloon angioplasty or bare metal stenting in vessels
The landmark trials BENESTENT1 and STRESS2 clearly demonstrated the advantage of stenting over balloon angioplasty in vessels with a diameter >= 3 mm. Whether stenting is similarly superior to balloon angioplasty in small vessels has been more controversial. The worse outcome of small vessel stenting was clearly demonstrated by Akiyama and coworkers.3 In their retrospective study of 1298 patients enrolled between 3/93 and 5/96, they found that stenting small vessels (mean vessel diameter of 2.64 mm) was associated with a higher restenosis rate (32.6% vs 19.9%, pWhat are Small Vessels and Why are They Unique? The definition of small vessel has varied considerably from one trial to the next. Of the 15 trials of small vessel intervention reviewed for this article (Table), 6 (40%) defined small vessel as any intervened upon segment of coronary artery Is the Vessel Truly as Small as it Looks Angiographically? Intravascular ultrasound (IVUS) has taught us that angiographically determined vessel size can be deceiving. Although a proximal or mid LAD, circumflex or right coronary artery may appear to be Pathophysiology of Restenosis After Stenting Small Vessels Achievement of an immediate increase in vessel lumen diameter (acute gain), without significant renarrowing of the vessel over time (late loss) determines the ultimate clinical success or failure of all coronary interventions. It is not surprising that the extent of acute gain predicts target lesion revascularization rate (TLR). Although stenting confers a clear advantage in acute gain compared with balloon angioplasty, it actually results in more late loss. This is because the metal tines of the deployed stent cause damage to the vessel intima and media, and this stimulates more intimal hyperplasia (scar tissue growing between the tines of the stent) and therefore late loss due to encroachment of the lumen of the vessel. IVUS studies have taught us that all bare metal stents produce a late loss of between 0.8 and 1.0 mm. This tissue encroachment presents a greater problem in small vessels than larger vessels (Figure 2), and therefore more clinically apparent restenosis. For example, if a stent is placed in a 2.0 mm vessel and there is 1.0 mm of late loss at 6 months, the vessel lumen is narrowed 50%. This obstruction may limit adequate oxygen supply to the myocardium with increased demand. In contrast, if a stent is placed in a 3.0 mm vessel and there is 1.0 mm of late loss at 6 months, the vessel lumen is narrowed only 33%. In this case, the lumen is large enough to supply oxygen to the myocardium, even in the case of increased demand. Do Bare Metal Stents Reduce Restenosis in Small Vessels? Although the safety of stenting small vessel disease has been well established, the long-term clinical benefits seen in most of the randomized trials suggest no benefit over balloon angioplasty alone (Table). However, three trials published within the past 3 years have demonstrated benefit of stenting in small vessels.4-6 These recent studies may reflect the evolution of stent technology and deployment techniques. Controversy continues to exist surrounding stenting of more complex small vessel disease, especially in diabetic patients and in those with long lesions. In addition, the clinical trial data have yet to clarify in precisely what vessel size benefits can be expected. In the diabetic population, a study by Suwaidi and co-workers7 is the only trial that focused exclusively on this high-risk subgroup undergoing stenting of small vessel lesions. The study group was small, only 100 patients total, and results indicated no significant improvement with stenting. In a much larger study of 2602 patients, Elezi et al8 compared the outcomes among patients with symptomatic coronary artery disease and varying vessel sizes treated with stenting. These investigators confirmed prior data demonstrating a higher restenosis rate among those stented patients with the smallest vessel diameters. Importantly, they also identified that the concomitant presence of diabetes and long lesions dramatically increased the risk of restenosis after small vessel stenting. Although these data argue against small vessel stenting in higher risk groups such as diabetic patients and long lesions, the advent of drug-eluting stents for small vessels will likely change our current conservative approach (see below). Advances in Stent Design Strategies that limit injury to the vessel wall would seem to play a critical role in developing a stenting technology that would allow realization of the benefit of enhanced early gain without substantial late loss in treating small vessel disease. One such strategy is the development of thin-strutted stents. Although not specifically a trial of small vessels, The ISAR-STEREO-2 trial by Pache and coworkers9 addressed the issue of whether the thin-strutted Multi-Link stent (50 micron strut thickness) conferred any restenosis advantage compared to thick-strutted BX Velocity stent (140 micron strut thickness). In 611 patients randomized between the two interventions, the thin strutted stent was clearly superior with a restenosis rate of 17.9% compared to 31.4% in the thick-strut group (p p=0.002). Theoretically, the benefits of thin struts should be evident in small vessels as well. In vessels with diameters between 2.75 and 3.0 mm, Briguori and co-workers6 (Figure 3) demonstrated significantly less restenosis following stenting with a thin strutted stent (=0.10 mm). However, no significant benefit was observed in vessels 2.51 to 2.75 or in those 5 compared a heparin coated small vessel stent to balloon angioplasty in 145 patients. Mean reference vessel diameter was 2.44 in the stent group and 2.38 mm in the balloon group (p=NS). Event free survival was significantly greater in the stent group 90.5 vs 76.1 in the angioplasty group (p p=0.15). Another trial by Haude and coworkers10 found similar outcomes in small vessels stented with a heparin-coated versus a bare-metal stent. Both stent groups demonstrated improved minimal luminal diameter over balloon angioplasty alone, but there was no difference in major adverse coronary events or restenosis. One potential explanation for the disparity in results between the positive Moer study and the negative Haude study is the fact that the Haude study focused on smaller vessels (2.0 to 2.6 mm), whereas the Moer study included patients with vessel diameters from 2.1 up to 3 mm. This disparity further underscores the challenge of treating vessels 2.6 mm and less. In spite of the above-mentioned apparent dependence on vessel size, a recent non-randomized study by Grenadier and coworkers11 using a phosphorylcholine-coated (PC-coated) stent demonstrated an acceptably low rate of major coronary events at 6 months in stenting vessels less than 2 mm. Phosphorylcholine is a component of the red cell membrane that is believed to decrease the likelihood of in-stent thrombosis. These results underscore the need for stents specifically designed for small vessels. However, randomized trials comparing these very small vessel stents to balloon angioplasty are needed. Garcia and coworkers12 studied the performance of the Pixel stent specifically designed for small vessels. In 350 patients with vessel diameter between 2.2 and 2.7 mm, the benefit of a pre-dilation strategy was compared to a direct stenting approach. Procedural success and 6-month outcomes were remarkably good in both groups, with a low TLR rate of 4.3% in the pre-dilation group and a 3.4% rate in the direct stenting group. There was a non significant trend toward a lower restenosis rate with direct stenting 16% vs 25%. Although not proving superiority of stenting small vessel disease over balloon angioplasty, these data suggest that excellent outcomes can result from using advanced stent technology developed specifically for small vessels. The specific advantage of direct stenting is encouraging but will require further study. Another recent advance in stent technology is the use of new alloys rather than the traditional stainless steel. Both the Guidant Multi-Link Vision stent (Figure 4) and the Medtronic Driver stent are made of proprietary alloys that incorporate cobalt and chromium. The advanced stents confers a number of advantages, including thinner stent struts, preserved visibility and enhanced flexibility. Although registry data for both of these stents have demonstrated excellent performance and clinical outcomes with low TLR rates, there has not yet been any randomized study comparing these stents to balloon angioplasty in vessels Drug-Eluting Stents for Small Vessel Lesions Drug-eluting stents will likely represent the most important technical advance in the management of small vessel disease. These devices work by incorporating an antiproliferative agent (e.g., sirolimus) into a polymer coating the surface of the stent. This permits the drug to gradually release into the vessel wall, thereby inhibiting intimal hyperplasia and the restenosis process. Although not exclusively a small vessel trial, data from the SIRIUS trial by Moses and coworkers13 demonstrated dramatic inhibition of intimal hyperplasia in the DES group compared to the bare metal stent group. Both angiographic restenosis and TLR rates were dramatically reduced for the trial as a whole and for all subgroups. Similar benefits were observed in the TAXUS trial presented by Dr. Gregg Stone at the Transcatheter Therapeutics Meeting in September 2003. The TAXUS trial employed a stent that released another potent antiproliferative agent, paclitaxel. These data also showed a dramatic reduction in restenosis, TLR and late loss compared with the bare metal stent. What is the evidence that drug-eluting stents are effective in small vessels? Although not specifically focused on small vessels, data are available from the cohort of patients receiving DES for vessels 14 randomized 352 patients with a long lesion (15 to 32 mm) in a small coronary artery (2.5 to 3.0 mm diameter) to the sirolimus-eluting Cypher stent or a bare-metal stent. At 8-month angiographic follow-up, minimum lumen diameter was significantly larger with the Cypher stent than with the control stent (2.22 vs 1.33 mm, pp=0.0001). Target lesion revascularization rates were also substantially reduced by the drug-eluting strategy (8.0 vs 22.6%, p=0.0002). These data have important implications for percutaneous revascularization of patients with long lesions in small vessels, a group with an extremely high risk of restenosis and need for repeat revascularization. Conclusions Small vessel disease is currently and will continue to be a challenging area for the interventional cardiologist. We are encouraged by early data from DES trials that demonstrate dramatic reduction in restenosis and clinical events in vessels 2.5 to 3.0 mm. However, it still remains to be proven whether a drug eluting stent will confer benefits over balloon angioplasty or bare metal stenting in vessels
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