Angioplasty and Stenting Procedure

In anticipation of carotid artery angioplasty and stenting, double antiplatelet therapy is initiated prior to the intervention to decrease the risk of thromboembolic complications. Most procedures are performed awake or under monitored anesthesia care, allowing for continuous neurological assessment. Following a diagnostic cerebral angiogram, a guide catheter or shuttle sheath is advanced into the common carotid artery. These delivery systems effectively maintain position and accommodate most stents. If more stability is necessitated, a “buddy” wire can be placed in the external carotid artery. Based upon the diagnostic angiograms, measurements of the stenotic diameter, the length of the lesion, and the diameter of the native common carotid and internal carotid arteries are obtained.

Next, embolic protection is secured in all attainable cases. Carotid plaques may be extremely friable, and even minor manipulation can result in distal embolization or vessel occlusion. Cerebral protection devices of varying construction are used to prevent embolic complications during CAS procedures. Most commonly, over-the-wire distal filters measured to the diameter of the native cervical internal carotid artery (ICA) are navigated past the stenotic lesion to capture embolic material (Fig. 47.6). Such devices allow continuous cerebral perfusion through pores in the filter baskets. Following angioplasty and stenting, the device is collapsed and withdrawn and embolic material retrieved. Alternatively, balloon occlusion devices may be used to completely prevent anterograde flow within the ICA. Any displaced material can be aspirated prior to balloon deflation. However, temporary carotid occlusion may not be well tolerated in all patients, limiting the applicability and utility of this strategy. Guide catheters with distal occlusion balloons may be inflated in the common carotid artery to achieve proximal control and distal flow reversal. Concomitant balloon inflation in the external carotid artery results in more thorough protection. Temporary proximal occlusion is generally performed when distal deployment of an embolic protective device (EPD) is not feasible owing to vessel size, tortuosity, or other anatomical restrictions.

Fig. 47.6 Over-the-wire distal embolic protection device (EPD). Filter is positioned in distal cervical internal carotid artery (beyond stenotic segment) to prevent embolic debris from reaching intracranial circulation.

Once embolic protection is achieved, balloon predilatation of tight stenoses can help ensure safe advancement of a self-expanding stent past the target lesion. Balloon inflation is done slowly to lessen the incidence of thromboembolism. Deflation must also be undertaken in a controlled, deliberate fashion. An experienced anesthesiologist and open communication are critical during this portion of the procedure. The endovascular surgeon must inform the anesthesia team of possible bradycardia associated with balloon inflation. This way, changes in the heart rate can be managed in a timely and proper fashion during angioplasty. Stent diameter is calibrated to 100% of the common carotid artery diameter, and length is measured to traverse the entire lesion with a margin of several millimeters both proximally and distally. Tapered stents are available to accommodate the larger diameter of the common carotid artery and the smaller lumen of the ICA. Depending on residual stenosis and distal perfusion, post-stent balloon dilatation may be undertaken. It is critical that balloon angioplasty remain within the confines of the stented arterial segment to prevent dissection of unprotected vascular intima (Fig. 47.7).

Fig. 47.7 Lateral angiogram demonstrating critical proximal internal carotid artery stenosis (left). Embolic protection device (EPD) is opened in distal cervical internal carotid artery (top of picture, middle). Following balloon dilatation, stent is positioned across stenotic segment (middle). Lateral angiogram showing stent deployed in distal common and proximal internal carotid artery, with minimal residual stenosis (left).

Clinical Trials

Since the advent of CAS procedures, there have been multiple clinical trials of relevance. Recent data suggest that carotid stenting procedures can be performed safely. Studies have demonstrated that CAS confers benefit in high-risk surgical patients and represents a rational alternative to CEA in a subset of lower-risk candidates.

When carotid angioplasty procedures were initially introduced more than 25 years ago, they were performed without stenting or distal embolic protection. Despite these limitations, early data suggested the promise of percutaneous intervention (Yadav et al., 1997). The first multicenter randomized trial that compared carotid angioplasty and CEA was the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS Investigators, 2001). This trial enrolled symptomatic patients with clinically significant (>80%) ICA stenosis. Only 26% of patients (those enrolled later in the study) underwent stenting in addition to transluminal angioplasty. Nonetheless, the 30-day risk of death or stroke was similar between the percutaneous and surgical groups.

The first multicenter randomized CAS study in the United States, the Carotid Wallstent Trial, was conducted using the tracheobronchial Wallstent device (Boston Scientific, Natick, Massachusetts) in symptomatic patients deemed standard risk for carotid endarterectomy. The trial was terminated prematurely, and although the outcomes for stenting and surgery were not statistically different, a strong trend favored surgery (Alberts, 2001). Many believe that relatively limited operator experience and early-generation nondedicated devices profoundly affected the outcome of the stenting cohort in this investigation. The efficacy of a nascent technique was being compared to that of a refined surgical procedure.

Through the 1990s, dedicated improved stent implants and EPDs were developed. Randomized CAS trials and registries targeted patients at high risk for endarterectomy, a cohort of individuals for which previous data were either lacking or revealed suboptimal surgical outcomes, The multicenter randomized Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial enrolled high-risk symptomatic and asymptomatic patients (Yadav, 2004). The primary endpoint (death, stroke, and myocardial infarction (MI) at 30 days, plus ipsilateral stroke or neurological death at 1 year) occurred at a rate of 12.2% for stenting and 20.1% for surgery patients (P = 0.05). In addition to achieving noninferiority of the primary outcome, the study demonstrated significant decrease in target-vessel revascularization (repeat procedures) and cranial nerve palsies in the CAS cohort (P <0.05). On the basis of these data, the FDA recommended approval of the Cordis PRECISE stent and ANGIOGUARD distal filter device (Cordis Corp., Miami Lakes, Florida) for symptomatic patients at high risk for CEA. Three-year follow-up data demonstrated no significant difference in long-term outcomes between CAS and CEA (Gurm et al., 2008). Following the SAPPHIRE trial, a series of multicenter registries was undertaken to gain approval (ongoing or completed) for similar device configurations marketed by various manufacturers. Based on the results from these trials and registries, the Centers for Medicare and Medicaid Services (CMS) approved coverage for CAS with distal embolic protection in high-risk symptomatic patients with stenoses of 70% or greater (Box 47.2). Additionally, coverage was provided for high-risk symptomatic patients with between 50% and 70% stenoses and high-risk asymptomatic patients with 80% or greater stenoses in accordance with category B investigational device exemption (IDE) clinical trials regulation and enrollment in CAS postapproval studies.

Supplementing the results generated by the SAPPHIRE trial and subsequent registry studies was the Carotid Revascularization Using Endarterectomy or Stenting Systems (CARESS) trial (CARESS Steering Committee, 2003). This nonrandomized investigation examined all patient subsets (not limited to high risk) and allowed practitioners to determine treatment allocation. In a more realistic clinical paradigm, the study sought to address whether CAS with distal embolic protection was comparable to CEA in patients with symptomatic and asymptomatic carotid stenosis. One-year outcome data demonstrated a trend toward fewer strokes and death in the CAS group, but the difference was not statistically significant (13.6% CEA versus 10% CAS).

Results from two randomized European trials were published simultaneously in 2006. The Stent Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial was a German study that enrolled symptomatic patients with stenoses greater than 50% (by NASCET criteria) and randomly allocated them to CAS or CEA (Ringleb et al., 2006; Stingele et al., 2008). The primary endpoint was ipsilateral stroke or death at 30 days. The steering committee terminated the trial early because of insufficient funding and the large projected number of patients required to demonstrate noninferiority. Nevertheless, primary outcome data appeared to demonstrate near equivalence among the two groups, despite a lack of EPD utilization in the majority of CAS patients.

The French Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial had inclusion criteria similar to SPACE (symptomatic, >60% stenosis) (Mas et al., 2006). Primary outcome included any stroke or death at 30 days. The investigation was terminated prematurely owing to objective concerns for safety and futility. The primary endpoint was achieved in 9.6% of CAS patients and 3.9% of CEA patients (P = 0.01). Detractors claim that the infrequent use of EPDs and deficiencies in the experience of stent operators (as few as five lifetime procedures) may have contributed to poor outcome in the CAS cohort. Nonetheless, the disparate SPACE and EVA-3S results further complicated questions regarding CAS indications in standard-risk symptomatic patients. Furthermore, a secondary analysis of pooled data generated from the SPACE and EVA studies failed to demonstrate that outcome event frequency (stroke or death) was directly related to the use of EPDs, suggesting that not all embolic complications could be avoided with device utilization (Tietke and Jansen, 2009).

The large randomized prospective Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) enrolled a total of 1326 symptomatic patients with greater than 50% stenoses and 1176 asymptomatic patients with greater than 60% stenoses deemed good candidates for either CEA or CAS (Hobson et al., 2004). Primary endpoints included death, stroke, and MI at 30 days or ipsilateral stroke at 1 year. Initial data suggested noninferiority of carotid artery angioplasty and stenting in this broad cohort. Findings indicated that the primary endpoint was not significantly different between the two arms (7.2% versus 6.8%). Additionally, the incidence of death, MI, or stroke at 30 days was similar between the two arms (5.2% versus 4.5%). Periprocedural strokes were significantly higher in the CAS arm (4.1% versus 2.3%), but the incidence of debilitating and major strokes was similar between the two arms (0.9% versus 0.7%). The incidence of MI was significantly lower in the CAS arm, compared with the CEA arm (1.1% versus 2.3%). Cranial nerve palsies were also significantly more common in the CEA arm. Long-term follow-up suggested that the incidence of ipsilateral stroke after the periprocedural period (approximately 4 years of follow-up) was similar between the two arms (2.0% versus 2.4%). Subgroup analyses indicated no difference based on gender, but there seemed to be evidence of effect modification by age such that patients 69 years of age or younger did better with CAS, whereas those aged 70 or older did better with CEA (Brott et al., 2010). These results will likely encourage expansion of indications for CAS procedures.

The International Carotid Stenting Study (ICSS), also known as CAVATAS II, is a European trial in symptomatic carotid stenosis patients. It was designed to revisit the questions raised in the original investigation while using stents in all percutaneous procedures (Ederle et al., 2010). Initial results were published at the same time the CREST data were revealed. ICSS enrolled 1713 patients and demonstrated a higher incidence of ischemic stroke and related events after stenting. The incidence of stroke, death, or procedural MI was significantly elevated in the stenting group (8.5%) compared to that the endarterectomy group (5.2%). Risks of any stroke and all-cause deaths were higher in the stenting group than in the endarterectomy group. There was an increased number of cranial nerve palsies in the CEA group.

The conflicting initial results generated by the CREST study, which was performed in the United States, and the largely European ICSS trial raised further questions regarding the indications for these two procedures. It must be noted, however, that the studies were designed (and hence executed) differently. While CREST evaluated both symptomatic and asymptomatic patients, ICSS examined only those with symptoms. Furthermore, the ICSS integrated no “lead-in time” or operator training period, a control measure incorporated into the CREST trial.

Several other trials addressed the indications for CAS in patients who are not high risk for surgery. The ongoing ACT I investigation compared stenting and endarterectomy in standard–surgical risk, asymptomatic patients (Ricotta and Malgor, 2008). The proposed Transatlantic Asymptomatic Carotid Intervention Trial (TACIT) aimed to incorporate an optimal medical management arm comparing the best modern medical treatment regimen to CEA and CAS (Gaines and Randall, 2005; Ricotta and Malgor, 2008). Results generated from investigations such as these will help clarify the future role for CAS procedures. Lessons learned from prior studies will likely translate to rapid development of novel technology and refinement of clinical parameters explored in future CAS trials.

With an extended array of optimal medical therapy, the treatment of marginal asymptomatic carotid stenosis cases by either CEA or CAS is now debatable. Prior to reporting of the CREST and ICSS results, CEA was the preferred treatment for both symptomatic and asymptomatic high-grade carotid artery stenosis—an efficacious procedure with a relatively low complication rate. CAS was reserved for symptomatic high-risk surgical candidates. Results from the CREST investigation will likely increase interest in ongoing and future CAS studies and translate to expanded future indications for CAS procedures.

Angioplasty/Stenting Procedure

Intracranial angioplasty and stenting with the Gateway/Wingspan system is most often performed under general endotracheal anesthesia. Dual antiplatelet therapy is initiated in anticipation of the procedure. A diagnostic cerebral angiogram is performed to assess degree of stenosis, length of diseased segment, flow restriction, and the presence of leptomeningeal collaterals. A shuttle sheath or guide catheter is used to maintain proximal position and accommodate the angioplasty/stenting platform. Some operators use a distal support catheter in patients with particularly tortuous anatomy. After a microcatheter/microguidewire system is advanced past the lesion, an exchange-length microwire is used to advance, in series, the balloon angioplasty and stent catheters to the level of stenosis. The lesion is initially dilated with a PTA balloon sized to 80% of the native vessel luminal diameter, using the slow inflation technique advocated by Connors and Wojak (Connors and Wojak, 1999). After initial vessel dilation, the balloon catheter is exchanged for the self-expanding stent system, which is deployed across the stenotic lesion. Post-stenting balloon dilation is discouraged by the manufacturer (Figs. 47.9 and 47.10). At the conclusion of the procedure, the average reported residual stenosis (30%) is less than that observed following PTA alone (40%) but more than noted after balloon-mounted stent deployment (10%) (Fiorella and Woo, 2007; Henkes et al., 2005). Follow-up angiograms have demonstrated restenosis rates exceeding 30%, presumably due to elastic recoil, myointimal hyperplasia, and vascular remodeling (Garas et al., 2001). Coating stents with antiproliferative agents such as sirolimus and paclitaxel has been effective in reducing restenosis rates in the cardiology literature (Ong et al., 2006; Stone et al., 2004). Several recent studies have demonstrated encouraging results for the treatment of ICAD patients with drug-eluting stents (Gupta et al., 2006; Qureshi et al., 2006). Difficult vessel navigation with more rigid stenting systems and prolonged postoperative treatment with dual antiplatelet therapies are among the potential limitations to the successful translation of drug-eluting technology to pathologies of the intracranial vasculature.

Fig. 47.9 Anteroposterior (top left) and lateral (bottom right) angiograms demonstrating critical tandem petrocavernous and supraclinoid left internal carotid artery stenoses with no filling of left anterior cerebral artery and diminished flow through right left middle cerebral artery.

Fig. 47.10 Same patient as in Fig. 47.9. Top x-rays demonstrate balloon positioned across petrocavernous stenosis (black marker is the midpoint of the balloon, left) and stents deployed across petrocavernous and supraclinoid lesions (right). Anteroposterior (left) and lateral (right) post-stenting angiograms on the bottom demonstrate increased flow through stenoses and filling of both anterior and middle cerebral arteries on left.

Clinical Application

There remains controversy as to whether intracranial stent placement is superior to primary angioplasty in the treatment of ICAD. Studies have addressed the angiographic and clinical outcomes associated with each procedure, but relatively few comparative investigations have been reported. A multi-institutional (three tertiary care centers) retrospective study compared the clinical outcomes between primary angioplasty and stent placement for symptomatic intracranial atherosclerosis (Siddiq et al., 2008, 2009). Stroke and combined stroke and/or death were identified as primary clinical endpoints during the periprocedural and follow-up period of 5 years. The authors noted significantly fewer residual stenoses in the stent-treated cohort, but there was no significant reduction in stroke or mortality among the patients who underwent stenting procedures.

In a systematic literature review and meta-analysis, Siddiq et al. (2009) compared primary angioplasty and stent placement in patients with symptomatic intracranial atherosclerosis. They noted technical success rates of 80% in the angioplasty group and 95% in the stent cohort. There was no difference in the perioperative stroke and death rate between the two treatment groups (9% angioplasty, 8% stent). The pooled incidence of 1-year stroke and death was 20% in patients treated with primary angioplasty and 14% in those treated with stenting, signifying a statistically significant difference in outcome. Also noted was a significantly higher restenosis rate in the primary angioplasty group. Importantly, the authors demonstrated no discernable effect of study publication year on the risk of stroke and death.

Debate remains as to the precise indications and preferred treatment strategies for symptomatic ICAD. The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study is an ongoing large-scale randomized investigation comparing intracranial angioplasty and stenting (Wingspan stent/Gateway balloon) and intensive medical management with optimal medical management alone. Patients with 70% to 99% intracranial stenosis who suffered a stroke or transient ischemic attack (TIA) within 30 days of enrollment are randomized and followed for up to 4 years. This marks the first large-scale randomized study comparing the efficacy of endovascular therapy and medical management in patients with ICAD (Rasmussen, 2009). Intracranial angioplasty with or without stenting is an emerging technique that may have a pivotal position in the treatment of symptomatic intracranial atherosclerosis. The results of SAMMPRIS and other ongoing investigations will better address the precise indications.

Ruptured Aneurysms

Following rupture of an intracranial aneurysm, recurrent hemorrhage occurs at a high frequency. Jane et al. (1985) documented that the incidence of rebleeding among patients with SAH and untreated aneurysms was 50% in the first 6 months and 3% per year thereafter. Because of the high risk of subsequent rupture, these aneurysms are nearly always treated urgently.

The randomized prospective multicenter International Subarachnoid Aneurysm Trial compared the efficacy of endovascular treatment with that of surgery in patients with ruptured intracranial aneurysms suitable for either treatment modality (Molyneux et al., 2002, 2005). A total of 2143 patients were randomized. Recruitment was prematurely terminated after a planned interim analysis demonstrated reduced disability in the endovascular treatment group. In an intention-to-treat analysis, the proportion of patients who were dead or disabled at 1 year was significantly lower in the endovascular therapy group compared to the surgical cohort. Additionally, the risk of perioperative seizures was lower following coiling procedures. However, the requirement for a second procedure was higher with endovascular treatment. The 1-year risk of rebleeding from the ruptured aneurysm was 2 per 1272 patient-years for individuals allocated to embolization and 0 per 1081 in the cohort allocated to open surgery. The investigators noted that the low rates of late rebleeding and potential periprocedural complications associated with retreatment in the endovascular group were unlikely to alter the treatment benefit at 1 year. They concluded that endovascular coil embolization of ruptured intracranial aneurysms when a patient has a good clinical grade (World Federation of Neurosurgical Societies grade I-III) and the aneurysm anatomy is suitable for endovascular treatment is more likely than not to lead to independent survival at 1 year those receiving neurosurgical treatment. Results may be generalized to good-grade patients harboring anterior circulation aneurysms. Statistical comparisons were difficult in poor-grade patients and those with posterior circulation aneurysms, as the vast majority of these individuals were not randomized due to treating physicians’ overwhelming preference for endovascular therapy.

To address issues regarding incomplete occlusion and recanalization following endovascular therapy, rerupture rates after treatment for aneurysmal subarachnoid hemorrhage were further investigated in the Cerebral Aneurysm Rupture After Treatment (CARAT) study (Johnston et al., 2008). All ruptured saccular aneurysms treated between 1996 and 1998 in nine institutions were evaluated for rerupture. A total of 1010 patients (711 surgically clipped, 299 treated by coil embolization) were contacted by written questionnaire or telephone. Rerupture of the treated aneurysm after 1 year occurred in one patient who underwent coil embolization (904 person-years of follow-up, 0.11% annual rate) and no patients treated with surgical clipping (2666 person-years). Aneurysm retreatment after 1 year was more frequent in the endovascular cohort. However, major complications were rare during follow-up treatment. The authors concluded that late events are unlikely to overwhelm differences between the procedures at 1-year follow-up.

Incidental Aneurysms

The decision matrix for treatment of incidentally discovered unruptured aneurysms is based on natural history data and the risk/benefit stratification for the applicable treatment modalities.