9. Management of Extracranial Carotid Disease and Intracranial Atherosclerosis (2023)

1. Protocols to ensure timely access to diagnostic services for evaluating carotid arteries.
2. Development of agreements and processes for rapid access to surgical consults, including a mechanism for expedited referrals as required for carotid interventions.
3. Ensure navigation of system is supported increasing patient compliance. Mechanims to increase compliance should be explored and assessed.

1. Proportion of stroke or TIA patients with moderate to severe (50 percent to 99 percent) symptomatic carotid artery stenosis who undergo a carotid revascularization procedure following an index stroke/TIA event. (KQI)
2. Proportion of stroke/TIA patients with moderate to severe (50 percent to 99 percent) carotid artery stenosis who undergo a carotid revascularization procedure following an index event within 2 weeks of first hospital or SPC assessment. (KQI)
3. Median time from onset of index ischemic stroke or TIA symptoms to carotid revascularization (days, hours). (KQI)
4. Proportion of stroke patients requiring carotid intervention who undergo the procedure within two weeks of the index stroke event.
5. Proportion of stroke patients with moderate carotid stenosis (50 percent to 69 percent) who undergo carotid intervention procedure following the incident stroke event.
6. Proportion of stroke patients with mild carotid stenosis (less than 50 percent) who undergo carotid intervention procedure following the incident stroke event.
7. Proportion of carotid endarterectomy patients who experience perioperative in-hospital stroke, acute myocardial infarction or death.
8. The 30-day in-hospital mortality rate after carotid endarterectomy and stroke rate by carotid occlusion severity.
9. Proportion of patients who undergo carotid endarterectomy within two weeks, between two and four weeks, between four weeks and three months, and between three and six months of stroke onset.
10. Proportion of patients who wait more than three months for carotid endarterectomy or whose surgery is cancelled because of long wait times. Proportion of patients who experience a subsequent stroke event or death while waiting for carotid endarterectomy.

Measurement Notes

• Time interval measurements should be taken from the time the patient or family reports as the time of stroke symptom onset to the actual date of surgery.
• The stroke onset time will depend on patient report or that of a reliable observer at the time of the event.
• Analysis should be stratified between those patients undergoing carotid stenting and those patients undergoing carotid endarterectomy, by severity of stenosis and by whether the patient had symptomatic or asymptomatic carotid artery disease.
• Data source for surgical date should be surgical note, nurses’ notes and discharge summary.
• In some cases, it may be more appropriate or relevant to record the time interval from the first time the patient has contact with medical care until the time of carotid surgery. This has occurred in cases where the patient was out of the country at the time of the stroke event and chose to return to Canada before seeking definitive medical intervention. It is important to note the nature of the start time when calculating turnaround times or intervention times.

Health Care Provider Information

• CSBPR: Acute Stroke Management, Neurovascular Imaging
• Question and Answers about carotid endarterectomy NINDS
• University of Oxford – Medical Sciences Division, Carotid Stenosis Tool. 1 year and 5-year risk of ipsilateral ischemic stroke predicted by model

Patient Information

• Heart & Stroke: Post-Stroke Checklist
• Heart & Stroke: Your Stroke Journey
• Heart & Stroke: Online and Peer Support
• Heart & Stroke: Atherosclerosis
• National Heart, Lung and Blood Institute

Management of Extracranial Carotid Artery Disease and Intracranial Atherosclerosis Evidence Table and Reference List

Table 9: Risk of recurrent stroke among patients with carotid stenosis ≥50% and recent stroke awaiting carotid endarterectomy or carotid stenting.

Carotid Endarterectomy

Carotid endarterectomy (CEA) has been shown to be beneficial for preventing stroke recurrence in patients who have sustained a minor stroke or TIA with ipsilateral high-grade carotid stenosis. There are three large trials comparing endarterectomy for symptomatic stenosis with best medical treatment in such patients: The North American Symptomatic Carotid Endarterectomy Trial (NASCET, 1991), the European Carotid Surgery Trial (ECST, 1998) and the Veterans Affairs Trial (Mayberg et al. 1991). The results of these three trials were pooled in a Cochrane review (Rerkasem & Rothwell 2011). The risk of any stroke or operative death at 5-years in patients with severe stenosis (70–99%) was significantly reduced in patients in the CEA group (RR=0.53, 0.42-0.67, p<0.0001, NNT=6) with an associated absolute risk reduction of 16.0%. For patients with moderate stenosis (50-69%) the risk was also reduced (RR=0.77, 0.63- 0.94, p=0.001, NNT=22). For patients with mild stenosis, there was no benefit of treatment. Perioperative death or stroke incidence was 7.0% (95% CI 6.2 to 8.0). The greatest benefit of treatment was found in men, patients aged 75 years or over, and patients randomised within two weeks after their last ischaemic event.

Carotid-artery angioplasty with stenting emerged (CAS) has emerged as an alternative to carotid endarterectomy in patients at high risk for complications for endarterectomy such as contralateral occlusion, advanced age or severe coronary artery disease. The percutaneous approach also avoids the risks of general anesthesia and the local complications of neck hematoma, infection, cervical strain and cranial nerve damage associated with endarterectomy and requires a shorter recovery period. Several large trials assessing the safety and effectiveness of CAS (without the use of embolic protection devices) have been conducted.

The risk of periprocedural death and stroke have been shown to be higher following CAS procedures compared with CEA. Zhang et al. (2015) included the results from 35 studies comparing CEA and CAS. Overall, the risk of the primary outcome (stroke or death within 30 days) was significantly higher with CAS (RR=1.51, 95% CI 1.32-1.74, p<0.001). The risk of any stroke or death did not differ significantly between groups at 2 or 3-year follow-up; however, the risk was significantly increased at 4- and 10-years’ follow-up for CAS-treated patients (RR=1.24, 95% CI 1.04-1.46, p=0.01 and RR=2.27, 95% CI 1.39-3.71, p=0.001, respectively). Brott et al. (2019) included the results from 4 RCTs (EVA-3S, SPACE, ICSS and CREST), and reported the risk of stroke or death was increased significantly during the periprocedural and post-procedural periods in the CAS group (11.4% vs. 8.3%; HR=1·45, 95% CI 1·20 to 1·75). The risk difference in the outcome of stroke or death between CEA and CAS favoured the CEA group at 1 year (3.1%), 3 years (2.8%), 5 years (3.0%), 7 years (3.7%) and 9 years (4.1%) after randomization. A recent Cochrane review (Müller et al. 2020) included the results of 22 trials of patients with symptomatic stenosis, who had experienced a minor stroke, those with asymptomatic stenosis or both asymptomatic and symptomatic carotid stenosis. The treatment contrasts included any CEA procedure vs. any endovascular technique (primarily stenting +/- protection devices). Among patients with symptomatic stenosis, stenting was associated with a higher risk of death or any stroke within 30 days of treatment (OR=1.70, 95% CI 1.31- 2.19). In pre-planned subgroup analysis, using data from 6 trials, the risk of periprocedural death or stroke did not differ significantly between stenting and CEA in patients <70 years (OR=1.11, 95% CI 0.74 to 1.64), but was significantly higher in patients ≥70 years treated with stenting (OR=2.23, 95% CI 1.61 to 3.08). The risk of death or any stroke between randomization and 30 days after treatment or ipsilateral stroke until the end of follow-up was also higher in the stenting group. Among patients with asymptomatic stenosis, the risk of death or any stroke within 30 days of treatment was also significantly higher in those who received a stenting procedure compared with CEA (RR=1.72 95% CI 1.00 to 2.97), while there was no significant difference between groups for the other primary or secondary outcomes. The authors suggested that for patients with symptomatic stenosis, the combined procedural safety and long-term efficacy profile favours CEA, while in patients with asymptomatic carotid stenosis, there may be a small increase in the risk of stroke or death within 30 days of treatment associated with stenting, but further trials are necessary to provide additional data.

The Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy (SPACE) Trial included 1,200 patients, with symptomatic carotid artery stenosis, who had experienced TIA or moderate stroke within 180 days and with severe carotid artery stenosis (≥ 50% according to NASCET) (Ringleb et al. 2006). Patients were randomized to receive CAS (27% used embolic protection devices) or CEA after a median delay of 4-5 days. The trial was stopped prematurely due to concerns regarding funding and futility. There were no differences between groups on either any of the primary outcomes of 30-day ipsilateral stroke or death, or any of the secondary outcomes (disabling stroke or death from any cause within 30 days, disabling stroke, or procedural failures).

The Asymptomatic Carotid Trial (ACT 1) (Rosenfield et al. 2016), a noninferiority trial was stopped early due to slow enrolment. While the protocol aimed to recruit 1,658 patients, data from only 328 patients were available for follow-up assessment at 5 years. At one year, the occurrence of the primary outcome (composite of death, stroke, or myocardial infarction within 30 days of the procedure or ipsilateral stroke within 1 year of the procedure) was 3.8% for stenting group compared with 3.4% for CEA group. The threshold of a 3%-point difference for inferiority was not exceeded (upper 95% CI for difference was 2.27%), suggesting that CAS was not inferior to endarterectomy. Survival from 30 days to 5 years was not significantly different between groups (87.1% stenting group vs. 89.4% CEA group, p=0.21).

The International Carotid Stenting Study (ICSS) trial enrolled 1,713 patients >40 years, with symptomatic carotid artery stenosis ≥50% using the NASCET criteria (Ederle et al. 2010). Between randomization and 120 days, stenting was associated with an increased risk of stroke, death or procedural myocardial infarction, (8.5% vs. 5.2%, HR=1.69, 95% CI 1.16-2.45, p=0.006) any stroke (7.7% vs. 4.1%, HR=1.92, 95% CI 1.27-2.89, p=0.002), any stroke or death (8.5% vs. 4.7%, HR=1.86, 95% CI 1.26-2.74, p=0.001) and all-cause mortality (2.3% vs. 0.8%, HR=2.76, 95% CI 1.16-6.56, p=0.017). In the long-term study analysis Bonati et al. (2015) reported that after a median duration of 4.2 years the risk of any stroke was significantly increased in the stenting group (HR=1.71, 95% CI 1.28 -2.3, p=0.0003), while stenting was not associated with an increased risk of fatal or disabling stroke (HR=1.06, 95% CI 0.72-1.57, p=0.77). There was also a significantly increased risk of the outcome of periprocedural stroke/procedural death or ipsilateral stroke during follow-up (HR=1.72, 95% CI 1.24-2.39, p=0.001).). In both the per protocol and intention-to-treat analyses, the cumulative 5-year stroke risk was significantly higher in the stenting group (HR=1.53, 95% CI 1.02-2.31 and HR=1.71, 95% CI 1.28-2.30, respectively), while the 5-year risk of fatal or disabling stroke was not increased. The distribution of modified Rankin Scores was similar between groups.

Increasing experience of an operator or hospital has been shown to reduce the number of adverse events. Poorthuis et al. (2019) included the results of 87 studies examining the association between operator or hospital volumes and outcomes after carotid revascularization procedures. The risk of the primary outcome (procedural death or stroke within 90 days) was significantly lower among high-volume operators following both CEA and CAS procedures (CEA: unadjusted RR=0.59, 95% CI 0.42–0.83; 9 cohorts and CAS: unadjusted RR=0.50, 95% CI 0.32–0.79; 1 cohort), although there was wide variability in the descriptions of low and high-volume operators.

Cervical Artery Dissection

While the incidence of cervical artery dissections (CeAD) is relatively low, estimated to be between 2.6 to 2.9 per 100,000, CeAD is over-represented among persons less than 45 years (Weimar et al. 2010). Given the increased risk of recurrent stroke associated with CeAD, treatment with either antiplatelets or anticoagulants for at least 3 months is recommended. Based on the results of the Cervical Artery Dissection in Stroke (CADISS) Study (Markus et al. 2015), treatment with either agent appears to be equally effective for the prevention of recurrent stroke. In this trial, 250 patients with extracranial carotid or vertebral artery dissection were randomized, within 7 days of the event, to receive antiplatelet agents (dipyridamole, aspirin or clopidogrel, alone or in combination) or anticoagulant therapy (UFH, LMWH, followed by warfarin, with a target INR of 2-3), for the study duration. At the end of 3 months, the frequency of the primary outcome (stroke or death), was similar between groups. There were 4 recurrent strokes (3 antiplatelet vs. 1 anticoagulant) and no deaths in either group. There was a single case of major bleeding in the anticoagulant group. At one year (Markus et al. 2019), the risks of ipsilateral stroke, ipsilateral stroke or TIA, any stroke or TIA, or any stroke or death were similar between groups in both the intention-to-treat and per-protocol analyses. Among 181 patients who had MRI or CTA imaging performed at baseline and repeated at 3 months, there was no difference in the presence of residual narrowing or occlusion between those receiving antiplatelet therapy (n = 56 of 92) vs those receiving anticoagulant therapy (n = 53 of 89) (p = .97).

Similar findings were reported in a meta-analysis including the results of 34 non-randomized studies examining the same treatment contrast (Menon et al. 2008). There were 13/185 (7.0%) in the antiplatelet group and 17/447 (3.8%) in the anticoagulant group who suffered a TIA or stroke. The risk difference between groups was not significant (5%, 95% CI -1% to 11%, p = 0.11). The use of novel oral anticoagulants (NOAC) for the prevention of recurrent stroke following CAD has not been well studied. There are no RCTs to date. In a retrospective study (Caprio et al. 2014) including 149 patients with CAD, who were prescribed antithrombotic medication at hospital discharge, there were 2 recurrent strokes during a median of 7.5 months follow-up in the NOAC group compared with one each in the anticoagulant (AC) and antiplatelet (AP) groups. There were significantly fewer major hemorrhagic events in the NOAC group (0 vs. 8 [AC] and 1 (AP], p=0.034).