- Email: [email protected]
Embolic Protection in Carotid Artery Stenting: New Options
Embolic Protection in Carotid Artery Stenting: New Options D. Christopher Metzger, MD, FACC Carotid artery stenting (CAS) has emerged as an attractive alternative to carotid endarterectomy (CEA) in patients with carotid disease who are at high risk for CEA. With increasing experience and improved technique, results in CAS patients have improved consistently over time in several clinical trials. Carotid stenting is clearly not inferior to CEA in appropriately selected high-CEA-risk patients treated by experienced operators. With improving results, CAS now has the potential to be considered “front-line therapy” even in standard-risk CEA patients, as demonstrated in CREST and as being studied in ongoing trials, such as the ACT I trial. Successful, low-risk CAS can only be performed if distal embolization is minimized during this procedure. This can be accomplished only with appropriate patient and case selection, adequate operator training and experience, and meticulous attention to procedural detail. Embolic protection devices (EPDs) are an important cornerstone of low-risk CAS. There are well-established, study-validated embolic protection systems available for CAS. Four new EPD options have been introduced in the United States over the past 3 years. Results with these newer devices appear to be extremely promising, with low event rates seen in high-risk clinical patients. This article will offer a practical review of techniques to decrease distal embolization during CAS. We will review patient selection and provide a “cookbook” approach to procedural technique, emphasizing techniques unique to each of the various EPD systems currently available. We will also introduce the newer options in EPDs, provide practical tips on their use, and contrast their use and results with that of the existing EPD systems. We will provide practical procedural techniques that incorporate the use of various EPDs into strategies that will reduce distal embolization during CAS and also provide pertinent data referencing results of these devices seen in clinical trials. Tech Vasc Interventional Rad 14:86-94 © 2011 Elsevier Inc. All rights reserved. KEYWORDS carotid endarterectomy, carotid artery stenting, embolic protection device, activated clotting time, Center for MediCare and MediCaid Services, common carotid artery, internal carotid artery, external carotid artery, Major Adverse Events
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troke is a devastating clinical problem affecting a large number of patients. It is the third leading cause of death and the leading cause of disability in the United States.1 It is estimated that up to 30% of ischemic strokes are caused by obstructive carotid atherosclerosis.2 Carotid endarterectomy (CEA) has been proven to be superior to medical therapy alone in carefully selected patients with symptomatic and asymptomatic obstructive carotid stenosis with procedures performed by experienced operators at high-volume centers.3-5 However, many patients with carotid disease are at Wellmont CVA Heart Institute, Kingsport, TN. Address reprint requests to: D. Christopher Metzger, MD, FACC, Cardiovascular Associates, 2050 Meadowview Parkway, Kingsport, TN 37660. E-mail: [email protected].
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increased risk for CEA, and these patients were not included in the trials establishing the superiority of CEA over medical therapy. Carotid artery stenting (CAS) has emerged as an attractive alternative to CEA in patients at increased risk for CEA. The SAPPHIRE randomized trial6 demonstrated noninferiority of CAS compared with CEA in high-risk CEA patients in the best North American randomized trial. Several other studies have demonstrated noninferiority or superiority of CAS outcomes compared with historical controls of CEA performed in high-risk CEA patients, even in early trials of CAS.7 CAS is now being studied as a potential first-line therapy for obstructive carotid disease, with the recently published CREST study demonstrating equivalent long-term clinical outcomes in standard-risk patients treated with CAS compared with CEA in another trial with experienced oper-
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Figure 1 (A) Improving results of CAS over time. Major Adverse Events (MAE) composite of death, stroke, and myocardial infarction at 30 days. (B) ACT1 Carotid Trial “Lead In” data.
ators in both arms.8 Finally, with improving technology, increased operator experience, and improved patient selection, CAS results have improved consistently, such that the last 4 approval trials in the United States have extremely low event rates, even in high-CEA-risk patients (Fig. 1). To reduce complications during CAS, it is important to minimize or eliminate embolic events that occur during the procedure. The brain is a sensitive end organ. Embolic protection devices (EPDs) reduce embolic events during CAS and are a mandatory part of this procedure. In the United States, embolic protection use is mandated by Center for Medicare and Medicare Services (CMS) for reimbursement, and all important North American trials require their use during CAS. This article will address new options for embolic protection. However, it is extremely important to remember that no embolic protection system can completely prevent embolic events during the procedure. Embolic events can occur during
angiography and before placement of the EPD, during placement of the EPD, or even with a system in place. Therefore, we must devise strategies to minimize the potential for embolization during this procedure. Low-risk CAS can only occur if we carefully select the patients to be treated and have appropriately trained, experienced operators perform these procedures. In addition, meticulous technique and attention to detail during the entire CAS procedure are paramount. Embolic protection systems will contribute to the safety of the procedure when used in combination with this strategy. This article will offer a practical approach to decrease embolization during the CAS procedure. We will briefly discuss patient selection and operator experience and then review the angiography and stent procedure in its entirety, sharing experience gleaned from over 1000 CAS procedures performed at our institution, as well as incorporating the experiences of more superior operators. We will provide practical
D.C. Metzger
88 tips that we have found to be successful. We will then comment on specific strategies for the various new EPD systems and finish with a discussion of these new options and their relevance to CAS in the current era.
General Strategies to Reduce Complications Before discussing specific procedural techniques, 3 important concepts cannot be overemphasized: patient and case selection, operator experience, and attention to procedural detail. The significant improvement in CAS outcomes over time (Fig. 1) is likely, at least in part, because of the lessons learned from early carotid stenting in terms of patient selection and because of increased operator experience. We must select only the correct patients and anatomy for this procedure. Patients with poor cerebral reserve are not ideal candidates for CAS (or CEA). Dementia, short-term memory deficits, significant prior strokes, etc., render these patients more susceptible to minor insults during the procedure and these patients should be avoided in most cases. Other highrisk patient features for CAS include patients with renal dysfunction, highly anxious patients, and highly symptomatic patients. Octogenarian patients are in general at increased risk for this procedure, although there have been studies suggesting favorable outcomes if patients have good cerebral reserve and favorable anatomy and if the procedure is performed by high-volume operators.9,10 High-risk anatomy will increase embolic event rates. In general, the more calcification and/or disease that must be traversed to access the carotid lesion, the higher the event rate. This includes angulated carotid arches and common carotid arteries (CCAs), especially if there is calcific plaque. Increased catheter manipulation prior to treating the carotid stenosis will result in poorer outcomes. Patients with lesionspecific characteristics such as heavy circumferential calcification are at increased risk and should be avoided. Additionally, a sharp entry angle into the internal carotid artery (ICA; increased angle between the CCA and the ICA) or an increased exit angle after the carotid lesion should be treated with significant caution or avoided. Highly tortuous vessels with poor landing zones for the stents and/or distal EPDs also are poorly suited for CAS. Many other lesions are unsuitable for CAS, including string signs, mobile thrombus, and major intracranial stenoses on the ipsilateral side. Operator training and experience are also paramount. In general, operators should have significant experience with endovascular procedures in other noncarotid areas before embarking on CAS training. Most would consider an absolute minimum of 50-100 endovascular procedures elsewhere before starting with carotid stenting training. Operators must have thorough training in neuroanatomy and neurophysiology and carotid angiography prior to starting with carotid stenting. Significant prior experience with 0.014-inch wire technology, rapid exchange techniques, and EPD use in other territories is crucial before CAS training. Additionally, operators should have a large number of proctored cases with an experienced operator before performing CAS independently.
Most believe that this number should include involvement in 25 proctored, hands-on cases before independently performing these procedures. Operators must start with straightforward cases early in their learning curves. For all operators, the risk of CAS for each individual patient should be less than or equal to the risk of the natural history of the disease and/or the alternative therapy of CEA before proceeding. We should always consider the relatively benign course of CAS, especially in asymptomatic patients, and the excellent alternative of CEA. At no time should we take a patient who is at high risk for CAS but low risk for CEA and proceed with CAS.
Procedure: From Angiograms to Start of CAS Attention to particular CAS detail starts before the patient’s arrival in the angiography suite and continues upon their arrival. All patients are seen for formal carotid stent consultation by the operator before the procedure, with careful description of the procedure as well as the risks and benefits. The patient is brought to the angiography suite well hydrated and usually having withheld blood pressure medicines on the day of the procedure, with dual antiplatelet therapy for at least 1 week before the procedure, which are confirmed upon the patient’s arrival. A Foley catheter is usually placed. The patient’s head is placed on a molded carotid pillow. A sticker is placed on the patient’s target neck side (we use a cut segment of a marker catheter attached to a piece of tape, which serves as an additional marker in addition to the bony landmarks). A toy is placed in the patient’s contralateral hand and careful instructions are reviewed with the patient. For the vast majority of patients, no sedation is given. We first assess the aortic arch in all patients. For the vast majority of patients, this is done with an arch aortogram (exceptions would be readily available magnetic resonance angiography/computed tomography angiography images or knowledge of the arch from previous procedures). After the arch aortogram, a still frame of the aortogram is placed on our right screen for reference. At this point, we choose a sheath or guiding catheter that will be used for the procedure. (In our laboratory, a 6 French Shuttle sheath (Cook, Inc.) is used for 90-95% of cases. We choose an 8 French CBL modified guide when additional support and steering capabilities are needed, such as when there is marked angulation of the CCAs and/or a type III arch.) Immediately after the arch aortogram and the decision to use a sheath or guiding catheter, we exchange for the sheath or guiding catheter, which is placed in the descending thoracic aorta. We also administer anticoagulation early if we think there is a fairly high likelihood of proceeding with CAS based on the arch aortogram and preexisting data. We use bivalirudin for all of our cases and believe that the predictable anticoagulation throughout the procedure and low bleeding risk are significantly advantageous. After placing the sheath or guiding catheter, we use 5 French 125-cm-length neurodiagnostic catheters for all procedures. We access the nontarget carotid vessel and advance the catheter over a 0.038-inch angled glidewire (the only exception would be use of a 0.035-inch glidewire for very
Embolic protection in carotid artery stenting tortuous CCAs where the extra support of the 0.038-inch glidewire is not helpful). We perform 2 angiograms of the nontarget ICA and then 2 sets of cerebral angiograms and assess collateral flow. Following this, the catheter is redirected over the 0.038-inch angled glidewire into the target vessel. (It should be emphasized that for every catheter exchange or wire insertion, aspiration is carefully performed, and all catheters are advanced or removed from the carotid arteries over a glidewire only.) After angiograms of the target carotid vessel, the decision is made whether to proceed with carotid stenting. When proceeding, anticoagulation is given immediately, if this has not already been administered, and an Activated Clotting Time (ACT) is confirmed. If the external carotid artery (ECA) and carotid bifurcation do not have significant disease, a road map is performed, and the angled glidewire and neurodiagnostic catheter are advanced into the ECA. The preplaced sheath or guiding catheter is advanced with the road map over the glidewire and neurodiagnostic catheter to the distal CCA (we rarely find it necessary to exchange for a stiffer wire if we are able to access the ECA with a glidewire and diagnostic catheter unless a proximal protection system will be used). Once the sheath is placed in the distal CCA, the glidewire and neurodiagnostic catheter are removed, and very careful aspirations and checks for air are performed. We then repeat a carotid angiogram with the sheath in place in the distal CCA (this is important to ensure that no tortuosity has been transmitted into the ICA, which may affect the anatomy, before selecting our equipment). Again, it should be emphasized that aspiration is performed for every catheter and wire exchange. Prolonged manipulation is avoided and if we are unable to access a CCA for more than 1 minute, the catheter is removed, flushed, and
Figure 2 Aortogram showing Type II-III arch.
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Figure 3 Guiding catheter to provide support when accessing CCA.
reintroduced or a different catheter is selected. Neurodiagnostic catheters are strongly preferred to cardiac catheters because of the radio-opaque, tapered hydrophilic tip and favorable curves. We use vertebral catheters for type I arches, JB1 or H1 catheters for mildly angulated vessels, and a Vitek catheter for the majority of others. Experience with additional catheters, such as the Simmons series or JB2, is also important for more angulated arches. The additional support of a steerable guiding catheter can be invaluable when needed for type III arches (Figs. 2-5).
Figure 4 Diagnostic catheter and glidewire in ECA.
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CAS with Distal EPD
Figure 5 Guide catheter advanced into CCA.
CAS Procedure: Techniques to Reduce Time and Distal Embolization We will discuss the specific techniques for distal EPDs and proximal protection separately below. However, certain principles apply to both strategies. As above, with the sheath or guiding catheter in place in the distal CCA, an angiogram is retaken and an unsubtracted still frame is placed on the monitor as a reference to show the bony landmarks. At this point, all devices to be used in the CAS procedure are selected and fully prepped. The EPD, guidewire, predilatation balloon, postdilatation balloon, stent, and recovery catheter are all prepped and placed in order. Adequate anticoagulation is confirmed, instructions are reviewed with the patient, and he/she is reassured. Importantly, there is minimal administration of contrast throughout the CAS procedure (we use it only for 2 road maps, as summarized below, and never during stent positioning). We also believe that predilatation should be performed in essentially all cases. (There is minimal risk of embolization during predilatation, and it takes very little time. In addition, for the larger stents, predilatation allows positioning of the stent without movement of the EPD and avoids a situation where the stent will not expand fully on initial deployment). We also tend to use larger-diameter stents and do not “skimp on stent length,” choosing a longer stent if there is any question to avoid the need for back-andforth manipulation of the stent during placement because restenosis is minimal with CAS. We carefully avoid overdilatation for the poststent portion of the procedure regardless of the method of EPD chosen. In general, the dwell time for the EPD should routinely be ⬍7 minutes with careful preparation and technique.
With all equipment prepped, a road map is performed. Using the road map, the lesion is wired and the EPD positioned and deployed. Using the same road map, predilatation is performed, usually with a 4.0 ⫻ 30 balloon at nominal pressure (or 3.5 ⫻ 30 balloon if it is a smaller vessel). Short inflation times are used. Following removal of this balloon and aspiration to look for air, a new road map is performed before stenting. The stent is placed using the road map as well as the prepositioned sticker and the bony landmarks. No contrast is administered with the stent in place because the other references listed are sufficient (Fig. 6). Next, postdilatation is usually performed with a 5 ⫻ 20 noncompliant balloon. Of note, we use higher magnification to position the balloon carefully within the stent, with no contrast needed. We avoid overdilatation. Following removal of the balloon, it is essential to aspirate carefully, looking for any air that was introduced into the sheath. After this, we believe it is important to perform 1 diagnostic angiogram with the distal EPD in place. This is done primarily to ensure that there is no slow flow, which would indicate a full basket. If there is slow flow, we always perform aspiration thrombectomy from the sheath to the proximal portion of the EPD to remove any suspended debris from this column and then remove the EPD, which will almost always result in the restoration of normal flow pattern. Complete carotid and cerebral angiograms are then performed. Before removing the sheath from the CCA, we perform all neurologic checks (we want to avoid removing the sheath in case there is any consideration for additional angiograms needed and/or neurorescue). After we confirm normal neurologic checks, the sheath is removed carefully over a
Figure 6 Deploying stent utilizing roadmap and landmarks.
Embolic protection in carotid artery stenting
Figure 7 MoMa ECA balloon as a landmark.
glidewire, and we perform aspiration of the sheath during removal from the CCA.
CAS Using Proximal Embolic Protection The same principles discussed above apply to CAS with proximal protection, with the following modifications (of note, proximal embolic protection in general is much easier than perceived in the general CAS community). After angiography of the target ICA is completed, the lesion is assessed for its potential for proximal EPDs. In general, one hopes for collateral support to the treated hemisphere (known either from collateral support from the other hemisphere already assessed on cerebral angiography or from an ipsilateral posterior communicating artery). In addition, a patent ECA and no significant disease in the carotid bifurcation are needed to allow safe passage of the ECA balloon into the ECA. If proximal protection is chosen, the glidewire and neurodiagnostic catheter are advanced into the ECA using road mapping. This catheter is used to exchange for an exchange-length supportive wire (we use a Supracore wire). The neurodiagnostic catheter is removed, and a 9 French long sheath is placed. Via the 9 French sheath and over the supportive wire, the proximal embolic protection system is advanced such that the ECA balloon is positioned in the proximal ECA. Position is carefully assessed before removal of the supportive wire (the wire cannot be reinserted coaxially through the 2 balloons). As above, it is essential to have all equipment prepped and ready before initiating protection. The operator’s favorite 0.014-inch coronary guidewire is chosen (we use a Whisper wire). This is positioned within the device (before the end of the CCA balloon), but is not advanced across the lesion until protection is established. We review the procedure with the technician and operator
91 before initiating protection. After this, the ECA balloon is inflated. Next, an unsubtracted angiogram is performed with the ECA balloon inflated. A still image of this angiogram is obtained and placed as a reference (Fig. 7). (Importantly, the ECA balloon provides another excellent landmark for stent placement in addition to the bony landmarks. A small amount of antegrade flow may be seen in the distal ECA with this angiogram because of the end hole of this balloon.) With the 0.014-inch guidewire at the end of the catheter, a road map is performed. This road map will be left in place for the duration of the CAS procedure. After the road map, the CCA balloon is inflated (Fig. 8). The “stump pressure” is noted (a very low stump pressure may indicate suboptimal collateral support or a very tight ICA lesion and may be somewhat more predictive of intolerance). Once the stump pressure confirms occlusion, the lesion is wired with the 0.014-inch guidewire (we use larger curves because this wire will sometimes tend to track the ECA balloon). Predilatation is performed, as above, followed by placement of the previously prepared stent. (The ECA balloon and bony landmarks serve as references in addition to the road map; Figs. 9 and 10.) The lesion is postdilatated as needed, as discussed above. After this, aspiration is slowly performed with three 20-cc syringes (in the rare instance that blood cannot be aspirated, an aspiration catheter is used). The third aspirated syringe is filtered. If there is no additional debris seen, the ECA balloon is deflated, followed by deflation of the CCA balloon. Carotid and cerebral angiograms are obtained, and neurologic checks are performed before removal of the proximal EPD. Unlike standard sheaths and guiding catheters, the wire cannot be reinserted (it will not necessarily go through both balloon end holes). The device is
Figure 8 Roadmap used for proximal protection CAS procedure.
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protection before placing a wire across the lesion, and there is no need to cross the stenotic ICA with a potentially bulkier EPD in the absence of protection. These devices allow the use of any 0.014-inch guidewire. Additionally, because no device is placed above the lesion, there is much less restriction on the landing zone distal to the lesion, making this an excellent choice in ICAs with significant tortuosity. Additionally, there is more protection in symptomatic lesions or lesions with a component of thrombus because protection is established before the lesion is engaged. Importantly, both the ARMOUR11 and the EMPIRE12 trials approved by the Food and Drug Administration (FDA; with the Medtronic MoMa and Gore flow reversal systems, respectively) showed excellent results in high-CEA-risk patients, with ⱕ3% stroke, death, and MI rates at 30 days for both systems. Significantly, these devices had excellent outcomes in the highest risk patients with very low event rates in both symptomatic patients and octogenarians (Fig. 11). Additionally, for experienced operators, the learning curve is very short, with no event rates seen in the roll-in phase of these studies and an average of only 1.4 roll-ins needed per site in these trials.
Figure 9 Stent deployed utilizing roadmap and landmarks.
simply pulled out and the ECA balloon easily passes through the placed stent. In the fairly uncommon event of neurologic intolerance, it is important to always perform aspiration before balloon deflation so that no debris is liberated. In general, the procedure can be completed and all neurologic intolerance will resolve once the balloons are deflated. If severe intolerance occurs early in the procedure, aspiration can be performed and the balloons deflated. The balloons can then be sequentially reinflated as described and the procedure completed. In addition, if the Gore flow reversal system is used, a venous sheath is needed for flow reversal (this is not needed for the Medtronic MoMa flow interruption system).
Other “New Options” for Embolic Protection in CAS The newest filter wire distal EPD is the Abbott Nav6 device. This device has an independent guidewire with a 0.019-inch tip and incorporates a nylon mesh into the nitinol basket. This device has improved visibility and shorter length compared with the prior generation. Importantly, it also has excellent results in clinical trials, with only a 1.8% stroke or death rate at 30 days in the PROTECT trial.13 This device is also used in the ACT I trial, with excellent results of 1.4% minor stroke rate at 30 days in the first 145 lead-in patients (data presented at VIVA 2007 by Drs Ken Rosenfield and John Matsomoro; see Fig. 1A).
New Options for Embolic Protection in CAS In the United States, there are 4 relatively new EPD systems available. These include the 2 proximal protection devices (the Gore flow reversal system and the Medtronic MoMa device). The Abbott Nav6 distal embolic filter and the Medtronic FiberNet unique distal protection system have also been approved within the past 3 years. Of note, in over 1000 high-CEA-risk patients, all 4 of these systems have excellent results (see Fig. 1). This likely represents not only the technical improvements of these devices, but also better case selection, lessons learned, and improved operator experience. We will briefly review the new EPD options.
Proximal Embolic Protection in CAS Proximal protection is very important to include in the CAS armamentarium because it offers significant theoretic advantages over distal EPD. These advantages include more complete protection throughout the CAS procedure. There is
Figure 10 Final angio.
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㫦 Endpoint Results 11㫦 30d Results (ITT & Full Population) 6%
ARMOUR 30d
ITT (220)
ITT + Roll-in (257)
4% 2%
0.9% 0.8%
1.4% 1.2%
Major Stroke
Minor Stroke
2.7% 2.3% 0.9% 0.8%
0.9% 1.2%
0.0% 0.0%
0% Death
MI
TIA
1° Endpoint cumulative MACCE
30d Results by Symptoms and Age (ITT) 30d Strokes
6% 3%
2 3% 2.7% 2.3%
30d MACCE
2.7% 3.2%
2 3% 2.3% 2.3% 2 3%
2 1% 75y 2.1%
2 1% 2.1%
0.0% 0.0% 0% ALL
Asymptomatics
Symptomatics
Age >75
Symptomatics & Age >75 75
Figure 11 ARMOUR Trial 30-day results.
Finally, the Medtronic FiberNet is a novel distal embolic protection mesh that is unique and distinct from the distal filter baskets. It has the advantage of being the shortest length distal embolic protection system and has excellent results in the EPIC trial.14 The results with all 4 newer EPD systems have excellent trial results, likely in part the result of design improvements discussed above. Additionally, these studies occurred later in the development of CAS where improvements in technique and experience likely also play a part. Other FDA-approved systems have well-validated results, including the Cordis Angioguard system. This system has been extremely well established in the landmark SAPPHIRE trial,6 as well as in extremely large “real-world registry trials,” including CASES PMS and the ongoing Sapphire WW trial,15 which has enrolled more than 10,000 patients. Additionally, the Angioguard has the shortest length of the available filter baskets and the smallest pore size. Other available devices include the ev3 Spider EPD, studied in the CREATE Trial (Fig. 1). This has the advantage of being the only distal ED that allows use of any 0.014-inch guidewire independently, making it potentially a good choice to cross difficult lesions. Other systems include the Abbott Acculink distal EPD, which is well validated in the landmark CREST8 and the ARCHER Trial7 and was the first commercially available FDA-approved EPD. Also available is the wellstudied Boston Scientific Filterwire.
Conclusions CAS results continue to improve over time, such that it is now not only an excellent treatment option for appropriate pa-
tients who are at high risk for CEA, but also a potential front-line therapy in standard-risk patients. The ACT I trial is another landmark randomized trial that should provide additional information in standard-risk patients comparing CAS with embolic protection to CEA with experienced operators in both arms. For low-risk carotid stenting, distal embolization during each phase of the procedure must be minimized. This can be accomplished through careful patient selection, maximized operator training and experience, and meticulous attention to careful CAS procedure. The newer EPD systems, in addition to the established previously available EPD systems, provide an increased inventory of devices to choose from as we individualize therapy for each patient to improve outcomes. The results of recently published and ongoing clinical trials with these new devices and increased operator experience should validate carotid stenting as a viable front-line therapy for appropriate patients with carotid artery disease treated by experienced operators.
References 1. American Heart Association: Heart Disease and Stroke Statistics, 2004 update. Available at http://www.americanheart.org/downloadable/ heart/1079736729696HDSStats2004Update REV. 3/19/04. pdf 2. Debakey MH: Carotid endarterectomy revisited. J Endovasc Surg 3:4, 1996 3. North American Symptomatic Carotid Endarterectomy Trial Collaborators: Beneficial effect of CEA in symptomatic patients and high-grade carotid stenoses. N Engl J Med 325:445-453, 1991 4. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study: Endarterectomy for asymptomatic carotid artery stenosis. JAMA 273:1421-1428, 1995 5. Randomized Trial of Endarterectomy for Recently Symptomatic Carotid Stenosis: Final results of the MRC European carotid surgery trial (ECST). Lancet 351:379-387, 1998
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94 6. Yadav JS, Wholey MH, Kuntz RE, et al: Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 351:14931501, 2004 7. Gray WA, Hopkins LN, Yadav J, et al: Protected carotid stenting in highsurgical-risk patients: the ARCHeR results. J Vasc Surg 49:258-269, 2006 8. CREST, Brott TG, Hobson RW, et al: Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 363:11-23, 2010 9. Roubin GS, Iyer S, Halkin A, et al: Realizing the potential of carotid artery stenting: proposed paradigms for patient selection and procedural technique. Circulation 113:2021-2030, 2006 10. White CJ, Metzger DC, Ansel GM, et al: Safety and efficacy of carotid stenting in the very elderly. Catheter Cardiovasc Interv 75:651-655, 2010 11. Ansel GM, Hopkins LN, Jaff MR, et al: Safety and effectiveness of the INVATEC MO. MA proximal cerebral protection device during carotid
12. 13. 14.
15.
artery stenting: results from the ARMOUR pivotal trial. Catheter Cardiovasc Interv 76:1-8, 2010 Hopkins LN: The EMPIRE trial results: Presented at TCT, October 17, 2008. Washington, DC Chaturedi S, Gray WA, Matsumara J. Safety outcomes for the PROTECT Carotid Artery Stenting Multicenter Study. Stroke 40:2, 2009 Myla S, Bacharach JM, Ansel GM, et al: Carotid artery stenting in high surgical risk patients using the FiberNet embolic protection system: the EPIC trial results. Catheter Cardiovasc Interv 75:817822, 2010 Massop D, Dave R, Metzger C, et al: Stenting and angioplasty with protection in patients at high-risk for Endarterectomy: SAPPHIRE World-Wide Registry in the First 2,001 patients. Catheter Cardiovasc Interv 73:129-136, 2009
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troke is a devastating clinical problem affecting a large number of patients. It is the third leading cause of death and the leading cause of disability in the United States.1 It is estimated that up to 30% of ischemic strokes are caused by obstructive carotid atherosclerosis.2 Carotid endarterectomy (CEA) has been proven to be superior to medical therapy alone in carefully selected patients with symptomatic and asymptomatic obstructive carotid stenosis with procedures performed by experienced operators at high-volume centers.3-5 However, many patients with carotid disease are at Wellmont CVA Heart Institute, Kingsport, TN. Address reprint requests to: D. Christopher Metzger, MD, FACC, Cardiovascular Associates, 2050 Meadowview Parkway, Kingsport, TN 37660. E-mail: [email protected].
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increased risk for CEA, and these patients were not included in the trials establishing the superiority of CEA over medical therapy. Carotid artery stenting (CAS) has emerged as an attractive alternative to CEA in patients at increased risk for CEA. The SAPPHIRE randomized trial6 demonstrated noninferiority of CAS compared with CEA in high-risk CEA patients in the best North American randomized trial. Several other studies have demonstrated noninferiority or superiority of CAS outcomes compared with historical controls of CEA performed in high-risk CEA patients, even in early trials of CAS.7 CAS is now being studied as a potential first-line therapy for obstructive carotid disease, with the recently published CREST study demonstrating equivalent long-term clinical outcomes in standard-risk patients treated with CAS compared with CEA in another trial with experienced oper-
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Figure 1 (A) Improving results of CAS over time. Major Adverse Events (MAE) composite of death, stroke, and myocardial infarction at 30 days. (B) ACT1 Carotid Trial “Lead In” data.
ators in both arms.8 Finally, with improving technology, increased operator experience, and improved patient selection, CAS results have improved consistently, such that the last 4 approval trials in the United States have extremely low event rates, even in high-CEA-risk patients (Fig. 1). To reduce complications during CAS, it is important to minimize or eliminate embolic events that occur during the procedure. The brain is a sensitive end organ. Embolic protection devices (EPDs) reduce embolic events during CAS and are a mandatory part of this procedure. In the United States, embolic protection use is mandated by Center for Medicare and Medicare Services (CMS) for reimbursement, and all important North American trials require their use during CAS. This article will address new options for embolic protection. However, it is extremely important to remember that no embolic protection system can completely prevent embolic events during the procedure. Embolic events can occur during
angiography and before placement of the EPD, during placement of the EPD, or even with a system in place. Therefore, we must devise strategies to minimize the potential for embolization during this procedure. Low-risk CAS can only occur if we carefully select the patients to be treated and have appropriately trained, experienced operators perform these procedures. In addition, meticulous technique and attention to detail during the entire CAS procedure are paramount. Embolic protection systems will contribute to the safety of the procedure when used in combination with this strategy. This article will offer a practical approach to decrease embolization during the CAS procedure. We will briefly discuss patient selection and operator experience and then review the angiography and stent procedure in its entirety, sharing experience gleaned from over 1000 CAS procedures performed at our institution, as well as incorporating the experiences of more superior operators. We will provide practical
D.C. Metzger
88 tips that we have found to be successful. We will then comment on specific strategies for the various new EPD systems and finish with a discussion of these new options and their relevance to CAS in the current era.
General Strategies to Reduce Complications Before discussing specific procedural techniques, 3 important concepts cannot be overemphasized: patient and case selection, operator experience, and attention to procedural detail. The significant improvement in CAS outcomes over time (Fig. 1) is likely, at least in part, because of the lessons learned from early carotid stenting in terms of patient selection and because of increased operator experience. We must select only the correct patients and anatomy for this procedure. Patients with poor cerebral reserve are not ideal candidates for CAS (or CEA). Dementia, short-term memory deficits, significant prior strokes, etc., render these patients more susceptible to minor insults during the procedure and these patients should be avoided in most cases. Other highrisk patient features for CAS include patients with renal dysfunction, highly anxious patients, and highly symptomatic patients. Octogenarian patients are in general at increased risk for this procedure, although there have been studies suggesting favorable outcomes if patients have good cerebral reserve and favorable anatomy and if the procedure is performed by high-volume operators.9,10 High-risk anatomy will increase embolic event rates. In general, the more calcification and/or disease that must be traversed to access the carotid lesion, the higher the event rate. This includes angulated carotid arches and common carotid arteries (CCAs), especially if there is calcific plaque. Increased catheter manipulation prior to treating the carotid stenosis will result in poorer outcomes. Patients with lesionspecific characteristics such as heavy circumferential calcification are at increased risk and should be avoided. Additionally, a sharp entry angle into the internal carotid artery (ICA; increased angle between the CCA and the ICA) or an increased exit angle after the carotid lesion should be treated with significant caution or avoided. Highly tortuous vessels with poor landing zones for the stents and/or distal EPDs also are poorly suited for CAS. Many other lesions are unsuitable for CAS, including string signs, mobile thrombus, and major intracranial stenoses on the ipsilateral side. Operator training and experience are also paramount. In general, operators should have significant experience with endovascular procedures in other noncarotid areas before embarking on CAS training. Most would consider an absolute minimum of 50-100 endovascular procedures elsewhere before starting with carotid stenting training. Operators must have thorough training in neuroanatomy and neurophysiology and carotid angiography prior to starting with carotid stenting. Significant prior experience with 0.014-inch wire technology, rapid exchange techniques, and EPD use in other territories is crucial before CAS training. Additionally, operators should have a large number of proctored cases with an experienced operator before performing CAS independently.
Most believe that this number should include involvement in 25 proctored, hands-on cases before independently performing these procedures. Operators must start with straightforward cases early in their learning curves. For all operators, the risk of CAS for each individual patient should be less than or equal to the risk of the natural history of the disease and/or the alternative therapy of CEA before proceeding. We should always consider the relatively benign course of CAS, especially in asymptomatic patients, and the excellent alternative of CEA. At no time should we take a patient who is at high risk for CAS but low risk for CEA and proceed with CAS.
Procedure: From Angiograms to Start of CAS Attention to particular CAS detail starts before the patient’s arrival in the angiography suite and continues upon their arrival. All patients are seen for formal carotid stent consultation by the operator before the procedure, with careful description of the procedure as well as the risks and benefits. The patient is brought to the angiography suite well hydrated and usually having withheld blood pressure medicines on the day of the procedure, with dual antiplatelet therapy for at least 1 week before the procedure, which are confirmed upon the patient’s arrival. A Foley catheter is usually placed. The patient’s head is placed on a molded carotid pillow. A sticker is placed on the patient’s target neck side (we use a cut segment of a marker catheter attached to a piece of tape, which serves as an additional marker in addition to the bony landmarks). A toy is placed in the patient’s contralateral hand and careful instructions are reviewed with the patient. For the vast majority of patients, no sedation is given. We first assess the aortic arch in all patients. For the vast majority of patients, this is done with an arch aortogram (exceptions would be readily available magnetic resonance angiography/computed tomography angiography images or knowledge of the arch from previous procedures). After the arch aortogram, a still frame of the aortogram is placed on our right screen for reference. At this point, we choose a sheath or guiding catheter that will be used for the procedure. (In our laboratory, a 6 French Shuttle sheath (Cook, Inc.) is used for 90-95% of cases. We choose an 8 French CBL modified guide when additional support and steering capabilities are needed, such as when there is marked angulation of the CCAs and/or a type III arch.) Immediately after the arch aortogram and the decision to use a sheath or guiding catheter, we exchange for the sheath or guiding catheter, which is placed in the descending thoracic aorta. We also administer anticoagulation early if we think there is a fairly high likelihood of proceeding with CAS based on the arch aortogram and preexisting data. We use bivalirudin for all of our cases and believe that the predictable anticoagulation throughout the procedure and low bleeding risk are significantly advantageous. After placing the sheath or guiding catheter, we use 5 French 125-cm-length neurodiagnostic catheters for all procedures. We access the nontarget carotid vessel and advance the catheter over a 0.038-inch angled glidewire (the only exception would be use of a 0.035-inch glidewire for very
Embolic protection in carotid artery stenting tortuous CCAs where the extra support of the 0.038-inch glidewire is not helpful). We perform 2 angiograms of the nontarget ICA and then 2 sets of cerebral angiograms and assess collateral flow. Following this, the catheter is redirected over the 0.038-inch angled glidewire into the target vessel. (It should be emphasized that for every catheter exchange or wire insertion, aspiration is carefully performed, and all catheters are advanced or removed from the carotid arteries over a glidewire only.) After angiograms of the target carotid vessel, the decision is made whether to proceed with carotid stenting. When proceeding, anticoagulation is given immediately, if this has not already been administered, and an Activated Clotting Time (ACT) is confirmed. If the external carotid artery (ECA) and carotid bifurcation do not have significant disease, a road map is performed, and the angled glidewire and neurodiagnostic catheter are advanced into the ECA. The preplaced sheath or guiding catheter is advanced with the road map over the glidewire and neurodiagnostic catheter to the distal CCA (we rarely find it necessary to exchange for a stiffer wire if we are able to access the ECA with a glidewire and diagnostic catheter unless a proximal protection system will be used). Once the sheath is placed in the distal CCA, the glidewire and neurodiagnostic catheter are removed, and very careful aspirations and checks for air are performed. We then repeat a carotid angiogram with the sheath in place in the distal CCA (this is important to ensure that no tortuosity has been transmitted into the ICA, which may affect the anatomy, before selecting our equipment). Again, it should be emphasized that aspiration is performed for every catheter and wire exchange. Prolonged manipulation is avoided and if we are unable to access a CCA for more than 1 minute, the catheter is removed, flushed, and
Figure 2 Aortogram showing Type II-III arch.
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Figure 3 Guiding catheter to provide support when accessing CCA.
reintroduced or a different catheter is selected. Neurodiagnostic catheters are strongly preferred to cardiac catheters because of the radio-opaque, tapered hydrophilic tip and favorable curves. We use vertebral catheters for type I arches, JB1 or H1 catheters for mildly angulated vessels, and a Vitek catheter for the majority of others. Experience with additional catheters, such as the Simmons series or JB2, is also important for more angulated arches. The additional support of a steerable guiding catheter can be invaluable when needed for type III arches (Figs. 2-5).
Figure 4 Diagnostic catheter and glidewire in ECA.
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CAS with Distal EPD
Figure 5 Guide catheter advanced into CCA.
CAS Procedure: Techniques to Reduce Time and Distal Embolization We will discuss the specific techniques for distal EPDs and proximal protection separately below. However, certain principles apply to both strategies. As above, with the sheath or guiding catheter in place in the distal CCA, an angiogram is retaken and an unsubtracted still frame is placed on the monitor as a reference to show the bony landmarks. At this point, all devices to be used in the CAS procedure are selected and fully prepped. The EPD, guidewire, predilatation balloon, postdilatation balloon, stent, and recovery catheter are all prepped and placed in order. Adequate anticoagulation is confirmed, instructions are reviewed with the patient, and he/she is reassured. Importantly, there is minimal administration of contrast throughout the CAS procedure (we use it only for 2 road maps, as summarized below, and never during stent positioning). We also believe that predilatation should be performed in essentially all cases. (There is minimal risk of embolization during predilatation, and it takes very little time. In addition, for the larger stents, predilatation allows positioning of the stent without movement of the EPD and avoids a situation where the stent will not expand fully on initial deployment). We also tend to use larger-diameter stents and do not “skimp on stent length,” choosing a longer stent if there is any question to avoid the need for back-andforth manipulation of the stent during placement because restenosis is minimal with CAS. We carefully avoid overdilatation for the poststent portion of the procedure regardless of the method of EPD chosen. In general, the dwell time for the EPD should routinely be ⬍7 minutes with careful preparation and technique.
With all equipment prepped, a road map is performed. Using the road map, the lesion is wired and the EPD positioned and deployed. Using the same road map, predilatation is performed, usually with a 4.0 ⫻ 30 balloon at nominal pressure (or 3.5 ⫻ 30 balloon if it is a smaller vessel). Short inflation times are used. Following removal of this balloon and aspiration to look for air, a new road map is performed before stenting. The stent is placed using the road map as well as the prepositioned sticker and the bony landmarks. No contrast is administered with the stent in place because the other references listed are sufficient (Fig. 6). Next, postdilatation is usually performed with a 5 ⫻ 20 noncompliant balloon. Of note, we use higher magnification to position the balloon carefully within the stent, with no contrast needed. We avoid overdilatation. Following removal of the balloon, it is essential to aspirate carefully, looking for any air that was introduced into the sheath. After this, we believe it is important to perform 1 diagnostic angiogram with the distal EPD in place. This is done primarily to ensure that there is no slow flow, which would indicate a full basket. If there is slow flow, we always perform aspiration thrombectomy from the sheath to the proximal portion of the EPD to remove any suspended debris from this column and then remove the EPD, which will almost always result in the restoration of normal flow pattern. Complete carotid and cerebral angiograms are then performed. Before removing the sheath from the CCA, we perform all neurologic checks (we want to avoid removing the sheath in case there is any consideration for additional angiograms needed and/or neurorescue). After we confirm normal neurologic checks, the sheath is removed carefully over a
Figure 6 Deploying stent utilizing roadmap and landmarks.
Embolic protection in carotid artery stenting
Figure 7 MoMa ECA balloon as a landmark.
glidewire, and we perform aspiration of the sheath during removal from the CCA.
CAS Using Proximal Embolic Protection The same principles discussed above apply to CAS with proximal protection, with the following modifications (of note, proximal embolic protection in general is much easier than perceived in the general CAS community). After angiography of the target ICA is completed, the lesion is assessed for its potential for proximal EPDs. In general, one hopes for collateral support to the treated hemisphere (known either from collateral support from the other hemisphere already assessed on cerebral angiography or from an ipsilateral posterior communicating artery). In addition, a patent ECA and no significant disease in the carotid bifurcation are needed to allow safe passage of the ECA balloon into the ECA. If proximal protection is chosen, the glidewire and neurodiagnostic catheter are advanced into the ECA using road mapping. This catheter is used to exchange for an exchange-length supportive wire (we use a Supracore wire). The neurodiagnostic catheter is removed, and a 9 French long sheath is placed. Via the 9 French sheath and over the supportive wire, the proximal embolic protection system is advanced such that the ECA balloon is positioned in the proximal ECA. Position is carefully assessed before removal of the supportive wire (the wire cannot be reinserted coaxially through the 2 balloons). As above, it is essential to have all equipment prepped and ready before initiating protection. The operator’s favorite 0.014-inch coronary guidewire is chosen (we use a Whisper wire). This is positioned within the device (before the end of the CCA balloon), but is not advanced across the lesion until protection is established. We review the procedure with the technician and operator
91 before initiating protection. After this, the ECA balloon is inflated. Next, an unsubtracted angiogram is performed with the ECA balloon inflated. A still image of this angiogram is obtained and placed as a reference (Fig. 7). (Importantly, the ECA balloon provides another excellent landmark for stent placement in addition to the bony landmarks. A small amount of antegrade flow may be seen in the distal ECA with this angiogram because of the end hole of this balloon.) With the 0.014-inch guidewire at the end of the catheter, a road map is performed. This road map will be left in place for the duration of the CAS procedure. After the road map, the CCA balloon is inflated (Fig. 8). The “stump pressure” is noted (a very low stump pressure may indicate suboptimal collateral support or a very tight ICA lesion and may be somewhat more predictive of intolerance). Once the stump pressure confirms occlusion, the lesion is wired with the 0.014-inch guidewire (we use larger curves because this wire will sometimes tend to track the ECA balloon). Predilatation is performed, as above, followed by placement of the previously prepared stent. (The ECA balloon and bony landmarks serve as references in addition to the road map; Figs. 9 and 10.) The lesion is postdilatated as needed, as discussed above. After this, aspiration is slowly performed with three 20-cc syringes (in the rare instance that blood cannot be aspirated, an aspiration catheter is used). The third aspirated syringe is filtered. If there is no additional debris seen, the ECA balloon is deflated, followed by deflation of the CCA balloon. Carotid and cerebral angiograms are obtained, and neurologic checks are performed before removal of the proximal EPD. Unlike standard sheaths and guiding catheters, the wire cannot be reinserted (it will not necessarily go through both balloon end holes). The device is
Figure 8 Roadmap used for proximal protection CAS procedure.
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protection before placing a wire across the lesion, and there is no need to cross the stenotic ICA with a potentially bulkier EPD in the absence of protection. These devices allow the use of any 0.014-inch guidewire. Additionally, because no device is placed above the lesion, there is much less restriction on the landing zone distal to the lesion, making this an excellent choice in ICAs with significant tortuosity. Additionally, there is more protection in symptomatic lesions or lesions with a component of thrombus because protection is established before the lesion is engaged. Importantly, both the ARMOUR11 and the EMPIRE12 trials approved by the Food and Drug Administration (FDA; with the Medtronic MoMa and Gore flow reversal systems, respectively) showed excellent results in high-CEA-risk patients, with ⱕ3% stroke, death, and MI rates at 30 days for both systems. Significantly, these devices had excellent outcomes in the highest risk patients with very low event rates in both symptomatic patients and octogenarians (Fig. 11). Additionally, for experienced operators, the learning curve is very short, with no event rates seen in the roll-in phase of these studies and an average of only 1.4 roll-ins needed per site in these trials.
Figure 9 Stent deployed utilizing roadmap and landmarks.
simply pulled out and the ECA balloon easily passes through the placed stent. In the fairly uncommon event of neurologic intolerance, it is important to always perform aspiration before balloon deflation so that no debris is liberated. In general, the procedure can be completed and all neurologic intolerance will resolve once the balloons are deflated. If severe intolerance occurs early in the procedure, aspiration can be performed and the balloons deflated. The balloons can then be sequentially reinflated as described and the procedure completed. In addition, if the Gore flow reversal system is used, a venous sheath is needed for flow reversal (this is not needed for the Medtronic MoMa flow interruption system).
Other “New Options” for Embolic Protection in CAS The newest filter wire distal EPD is the Abbott Nav6 device. This device has an independent guidewire with a 0.019-inch tip and incorporates a nylon mesh into the nitinol basket. This device has improved visibility and shorter length compared with the prior generation. Importantly, it also has excellent results in clinical trials, with only a 1.8% stroke or death rate at 30 days in the PROTECT trial.13 This device is also used in the ACT I trial, with excellent results of 1.4% minor stroke rate at 30 days in the first 145 lead-in patients (data presented at VIVA 2007 by Drs Ken Rosenfield and John Matsomoro; see Fig. 1A).
New Options for Embolic Protection in CAS In the United States, there are 4 relatively new EPD systems available. These include the 2 proximal protection devices (the Gore flow reversal system and the Medtronic MoMa device). The Abbott Nav6 distal embolic filter and the Medtronic FiberNet unique distal protection system have also been approved within the past 3 years. Of note, in over 1000 high-CEA-risk patients, all 4 of these systems have excellent results (see Fig. 1). This likely represents not only the technical improvements of these devices, but also better case selection, lessons learned, and improved operator experience. We will briefly review the new EPD options.
Proximal Embolic Protection in CAS Proximal protection is very important to include in the CAS armamentarium because it offers significant theoretic advantages over distal EPD. These advantages include more complete protection throughout the CAS procedure. There is
Figure 10 Final angio.
Embolic protection in carotid artery stenting
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㫦 Endpoint Results 11㫦 30d Results (ITT & Full Population) 6%
ARMOUR 30d
ITT (220)
ITT + Roll-in (257)
4% 2%
0.9% 0.8%
1.4% 1.2%
Major Stroke
Minor Stroke
2.7% 2.3% 0.9% 0.8%
0.9% 1.2%
0.0% 0.0%
0% Death
MI
TIA
1° Endpoint cumulative MACCE
30d Results by Symptoms and Age (ITT) 30d Strokes
6% 3%
2 3% 2.7% 2.3%
30d MACCE
2.7% 3.2%
2 3% 2.3% 2.3% 2 3%
2 1% 75y 2.1%
2 1% 2.1%
0.0% 0.0% 0% ALL
Asymptomatics
Symptomatics
Age >75
Symptomatics & Age >75 75
Figure 11 ARMOUR Trial 30-day results.
Finally, the Medtronic FiberNet is a novel distal embolic protection mesh that is unique and distinct from the distal filter baskets. It has the advantage of being the shortest length distal embolic protection system and has excellent results in the EPIC trial.14 The results with all 4 newer EPD systems have excellent trial results, likely in part the result of design improvements discussed above. Additionally, these studies occurred later in the development of CAS where improvements in technique and experience likely also play a part. Other FDA-approved systems have well-validated results, including the Cordis Angioguard system. This system has been extremely well established in the landmark SAPPHIRE trial,6 as well as in extremely large “real-world registry trials,” including CASES PMS and the ongoing Sapphire WW trial,15 which has enrolled more than 10,000 patients. Additionally, the Angioguard has the shortest length of the available filter baskets and the smallest pore size. Other available devices include the ev3 Spider EPD, studied in the CREATE Trial (Fig. 1). This has the advantage of being the only distal ED that allows use of any 0.014-inch guidewire independently, making it potentially a good choice to cross difficult lesions. Other systems include the Abbott Acculink distal EPD, which is well validated in the landmark CREST8 and the ARCHER Trial7 and was the first commercially available FDA-approved EPD. Also available is the wellstudied Boston Scientific Filterwire.
Conclusions CAS results continue to improve over time, such that it is now not only an excellent treatment option for appropriate pa-
tients who are at high risk for CEA, but also a potential front-line therapy in standard-risk patients. The ACT I trial is another landmark randomized trial that should provide additional information in standard-risk patients comparing CAS with embolic protection to CEA with experienced operators in both arms. For low-risk carotid stenting, distal embolization during each phase of the procedure must be minimized. This can be accomplished through careful patient selection, maximized operator training and experience, and meticulous attention to careful CAS procedure. The newer EPD systems, in addition to the established previously available EPD systems, provide an increased inventory of devices to choose from as we individualize therapy for each patient to improve outcomes. The results of recently published and ongoing clinical trials with these new devices and increased operator experience should validate carotid stenting as a viable front-line therapy for appropriate patients with carotid artery disease treated by experienced operators.
References 1. American Heart Association: Heart Disease and Stroke Statistics, 2004 update. Available at http://www.americanheart.org/downloadable/ heart/1079736729696HDSStats2004Update REV. 3/19/04. pdf 2. Debakey MH: Carotid endarterectomy revisited. J Endovasc Surg 3:4, 1996 3. North American Symptomatic Carotid Endarterectomy Trial Collaborators: Beneficial effect of CEA in symptomatic patients and high-grade carotid stenoses. N Engl J Med 325:445-453, 1991 4. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study: Endarterectomy for asymptomatic carotid artery stenosis. JAMA 273:1421-1428, 1995 5. Randomized Trial of Endarterectomy for Recently Symptomatic Carotid Stenosis: Final results of the MRC European carotid surgery trial (ECST). Lancet 351:379-387, 1998
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94 6. Yadav JS, Wholey MH, Kuntz RE, et al: Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 351:14931501, 2004 7. Gray WA, Hopkins LN, Yadav J, et al: Protected carotid stenting in highsurgical-risk patients: the ARCHeR results. J Vasc Surg 49:258-269, 2006 8. CREST, Brott TG, Hobson RW, et al: Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 363:11-23, 2010 9. Roubin GS, Iyer S, Halkin A, et al: Realizing the potential of carotid artery stenting: proposed paradigms for patient selection and procedural technique. Circulation 113:2021-2030, 2006 10. White CJ, Metzger DC, Ansel GM, et al: Safety and efficacy of carotid stenting in the very elderly. Catheter Cardiovasc Interv 75:651-655, 2010 11. Ansel GM, Hopkins LN, Jaff MR, et al: Safety and effectiveness of the INVATEC MO. MA proximal cerebral protection device during carotid
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artery stenting: results from the ARMOUR pivotal trial. Catheter Cardiovasc Interv 76:1-8, 2010 Hopkins LN: The EMPIRE trial results: Presented at TCT, October 17, 2008. Washington, DC Chaturedi S, Gray WA, Matsumara J. Safety outcomes for the PROTECT Carotid Artery Stenting Multicenter Study. Stroke 40:2, 2009 Myla S, Bacharach JM, Ansel GM, et al: Carotid artery stenting in high surgical risk patients using the FiberNet embolic protection system: the EPIC trial results. Catheter Cardiovasc Interv 75:817822, 2010 Massop D, Dave R, Metzger C, et al: Stenting and angioplasty with protection in patients at high-risk for Endarterectomy: SAPPHIRE World-Wide Registry in the First 2,001 patients. Catheter Cardiovasc Interv 73:129-136, 2009