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Endovascular Management of Chronic Cerebral Ischemia
Chronic cerebral ischemia may be the result of extracranial carotid or vertebral stenosis and/or intracranial arterial stenosis. This chapter focuses on intracranial arterial stenosis as well as extracranial vertebral artery stenosis. For an in-depth discussion of extracranial carotid stenosis, please refer to Chapter 60 , Carotid Revascularization. Intracranial atherosclerotic disease (ICAD) is estimated to be the underlying cause of 10% of all ischemic strokes and carries a first-year ipsilateral stroke rate of at least 11%. Twenty percent of all ischemic strokes involve the posterior circulation, and the most common area of vascular stenosis or occlusion in the setting of a posterior circulation stroke is the extracranial vertebral artery. Given these strong associations with stroke, ICAD and extracranial vertebral artery atherosclerotic disease have become prime targets for endovascular treatment.
Review of the Current Literature
Intracranial Atherosclerotic Disease
The goal of intracerebral and extracranial vertebral endovascular revascularization in the setting of atherosclerotic stenosis is ipsilateral stroke prevention. The results of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) and Vitesse Intracranial Stent Study for Ischemic Stroke (VISSIT) trials are the basis for the current guidelines regarding treatment of ICAD. Asymptomatic patients with intracranial atherosclerotic narrowing should not be offered endovascular treatment. Patients who remain symptomatic despite maximal medical therapy should be considered for endovascular therapy. The rationale leading up to these conclusions is discussed in the following paragraphs.
The utility of best medical therapy alone in the treatment of intracranial atherosclerotic disease was evaluated in the Warfarin-Aspirin Symptomatic Intracranial Disease Trial (WASID). In this study, patients with a history of stroke or transient ischemic attack (TIA) caused by an angiographically confirmed 50% to 99% intracranial artery stenosis were randomly assigned to receive aspirin (1300 mg; n = 280) or warfarin (target international normalized ratio 2.0–3.0; n = 289). The study was prematurely terminated because of higher death, major hemorrhage, and myocardial infarction rates in the warfarin group, without any primary endpoint benefit for either treatment (stroke/brain hemorrhage/vascular death other than stroke, 22.1% for aspirin vs. 21.8% for warfarin). Perhaps most importantly this study illustrated the high morbidity and lack of effective medical therapy for moderate to severe intracranial atherosclerotic stenosis at that time. The overall 1- and 2-year rates of ischemic stroke in the territory of the stenosed artery were 11% and 14%, respectively. Factors associated with increased stroke risk included stenosis greater than 70%, recent symptoms, and female gender. The risk of a recent index event (TIA or stroke) and the linear increase in stroke risk associated with the degree of stenosis is analogous to the risk stratification observed in cervical carotid artery disease, which some studies estimate approaches 20% for severe symptomatic stenosis. Similarly, the subgroup of patients with the most severe symptomatic disease in the WASID pilot study had a stroke rate of 18% at 1 year despite best medical therapy.
Endovascular stenting is another treatment option that has been studied for preventing recurrent stroke or TIA in patients with intracranial atherosclerotic disease. However, evaluation of the efficacy of intracranial angioplasty and stenting is limited by factors such as rapidly evolving technology, the wide variation in endovascular techniques, and heterogenous patient selection. Outcome after endovascular treatment for chronic cerebral ischemia is generally measured by technical success, incidence of restenosis, and early and long-term ipsilateral stroke rates. Technical success for intracerebral arterial and extracranial vertebral artery disease, defined as residual stenosis postprocedure of less than 50%, is on the order of 95%. Whereas the initial in-stent restenosis (ISR) rates were quite high (approaching 30% in one study ), more recent larger series have documented an ISR rate of approximately 7%. In estimating the overall risk of stroke and death associated with intracranial angioplasty with or without stenting, a Cochrane systematic review of 79 publications calculated the pooled periprocedural rate of stroke or death at 9.5%.
The SAMMPRIS trial compared aggressive medical management alone to intracranial stenting ( Fig. 62.1 ) plus aggressive medical management for the prevention of stroke in patients with symptomatic severe intracranial stenosis (70%–99%) of a major artery (middle cerebral, carotid, vertebral, or basilar arteries). In the context of the study, aggressive medical management consisted of aspirin 325 mg/day for the entire follow-up, clopidogrel 75 mg/day for 90 days after enrollment, intensive management of vascular risk factors (systolic blood pressure < 140 mm Hg, [<130 mm Hg if diabetic], low-density lipoprotein levels below 70 mg/dL), and lifestyle modification programs for all study patients. Recruitment was halted after 451 (59%) of the planned 764 patients were enrolled, owing to the higher risk of stroke and death detected in the stented group (14.7%) compared with the aggressive medical management alone group (5.8%) in the first 30 days of enrollment. When followed out to 3 years, the risk of stroke and death was 23% in the interventional group and 15% in the medical management group. The VISSIT trial followed SAMMPRIS. This was a multicenter, randomized study that looked at the use of a balloon-expandable intracranial stent in patients with symptomatic ICAD. The study randomized 112 patients, and followed them for 1 year after the procedure. It also showed an increased stroke/TIA rate in the endovascular treatment group versus the medical management group (36.2% at 1 year compared with 15.1% at 1 year). The results of these two studies led to a decrease in endovascular treatment of ICAD.
A meta-analysis looking specifically at endovascular treatment of 403 patients with symptomatic posterior circulation ICAD and comparing outcomes with 592 patients who underwent medical therapy was published in 2016. The authors demonstrated a stroke or death rate of 8.9/100 person-years in the endovascular arm (95% confidence interval [CI] 6.9–11.0) compared with 14.8/100 person-years in the medical management arm (95% CI 9.5–20.1). There were 16 intracerebral hemorrhage events (8 in each group). Stroke recurrence rate was 7.2 per 100 person-years in the endovascular arm (95% CI 5.5–9.0) versus 9.6 per 100 person-years in the medical arm (95% CI 5.1–14.1).
Vertebral Artery Stenosis
Ischemia affecting the vertebrobasilar circulation appears to be less common than that affecting the anterior circulation, representing about 20% of all TIAs and ischemic strokes. The main pathologic mechanism of vertebral artery stenosis is atherosclerosis. This can result in hemodynamic compromise secondary to vessel narrowing, most commonly from atheroma causing stenosis of the vertebral origin or distal embolization from atherosclerotic plaques most commonly at the proximal vertebral artery. Some studies have shown that patients with vertebrobasilar ischemia have a higher rate of early recurrent stroke than patients with anterior circulation disease. As in the anterior circulation, medical therapy is recommended as the initial treatment for vertebral artery stenosis. When patients are refractory to medical treatment, open surgical treatment is less commonly employed than endovascular therapy, given the relative ease of endovascular access to this area compared with open surgery.
ISR remains a concern in vertebrobasilar stenting. Recent studies out of Asia have estimated the incidence to range between 14.6 and 17.9%, although it should be noted that this pertains to angiographic stenosis, which is not necessarily symptomatic. Nonetheless, these patients should be followed with serial imaging studies after stenting to assess for ISR, which may necessitate extending duration of dual antiplatelet therapy. The main predictive factor of ISR in both of these studies was stent size, with a smaller stent being associated with a higher rate of ISR.
The Carotid and Vertebral Artery Transluminal Angioplasty Study included a subset of patients with vertebral artery stenosis in which medical management was compared with endovascular treatment. The trial failed to show a benefit of endovascular treatment of vertebral artery stenosis, but the numbers of patients included was small. More recent trials, the Vertebral Artery Ischemic Stenting Trial (VIST) and the Vertebral Artery Stenting Trial, focused specifically on vertebrobasilar lesions. These trials demonstrated that stenting of extracranial vertebrobasilar stenosis was associated with a very low rate of periprocedural complications (0% and 2%, respectively). This low complication rate was also noted in an earlier systematic review looking at 980 patients reporting a 1.1% periprocedural stroke rate. These recent trials also failed to definitively prove the benefit of angioplasty, with or without stenting, over best medical therapy, but they did show that extracranial stenting is as safe and efficacious as medical therapy. In particular, VIST (the largest and most recent of the randomized, controlled trials) showed a nonsignificant reduction in recurrent stroke risk in the stented group. A fatal or nonfatal stroke occurred in 5 patients in the stent group versus 12 patients in the medical group (hazard ratio [HR] = 0.4, 95% CI 0.14–1.13, P = .08). The follow-up was limited in the VIST study secondary to early termination due to funding issues. As further follow-up is presented, additional benefit may be seen in those patients on whom the intervention is performed.
In summary, the results of the cited studies point to the role of endovascular treatment in patients with ICAD and vertebral artery disease. It is clear that endovascular treatment has a role in the most severely affected patients who are failing medical management.
Endovascular Treatment
Relative clinical contraindications to endovascular management of chronic cerebral ischemia are related to the risk of cerebral angiography and include severe contrast allergy and chronic renal insufficiency. Both of these may be managed with appropriate premedication. Administration of diphenhydramine (50 mg, 1 hour preoperatively) and prednisone (50 mg at 24, 12, and 1 hour preoperatively) is effective contrast allergy prophylaxis. Renal insufficiency can be managed in consultation with the nephrology team, considering that the risk of a stroke in this patient population, if untreated, exceeds the potential risk of any induced acute kidney injury. Other relative clinical contraindications are related to the need for dual antiplatelet therapy for at least 3 months after stenting. These include allergy or intolerance (e.g., excessive bruising) to aspirin and clopidogrel therapy. Some centers test for platelet reactivity to aspirin and clopidogrel, although this is not uniform practice. If necessary the clopidogrel can be substituted for other antiplatelets (e.g., Prasugrel, Ticagrelor). The requirement for dual antiplatelet therapy, intended to prevent platelet aggregation, embolization, and stent thrombosis until stent endothelialization, also makes the urgent need for a major surgical procedure after the endovascular treatment a relative contraindication for stenting.
Relative anatomic contraindications for stenting procedures are usually manageable by experienced operators when present individually. However, as the number of anatomic difficulties accrues, the procedure becomes significantly higher risk, making medical management preferable to the endovascular approach. Anatomic relative contraindications include severe tortuosity, calcification, or atherosclerotic disease of the aortic arch and origins of the great vessels ( Fig. 62.2 ). These changes make endovascular access difficult and significantly raise the risk of thromboembolic complications. Great-vessel origin stenosis is manageable by angioplasty and stenting concurrently with treatment of the target vessel. Severe tortuosity and acute takeoff of the common carotid artery and severe tortuosity of the internal carotid artery make access for a guide catheter or sheath and delivery of angioplasty balloon and stent challenging. Radial access can be a useful approach for vertebrobasilar stenosis in particular. Other anatomic considerations, including tandem stenoses, unruptured intracranial aneurysms, and arteriovenous malformations, are not contraindications to endovascular therapy.
Poorly controlled hypertension and a large recent infarct raise the risk of postrevascularization intracerebral hemorrhage from reperfusion injury and hyperperfusion syndrome. Postponing revascularization therapy (endovascular or surgical) for at least 10–14 days after a moderate to large stroke and careful postoperative blood pressure control can effectively minimize these risks. Some authors advocate waiting as long as 3 weeks from the index event.
Intensive medical therapy, including combination antiplatelet and high-dose statin therapy, in the first weeks after a stroke may also facilitate plaque stabilization, lowering the thromboembolic risk associated with the endovascular approach. It is important to emphasize that both careful patient selection and periprocedural patient management is best performed in close conjunction with the stroke neurology team.
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