Endovascular Treatment of Extracranial Occlusive Disease

Introduction

Ischemic stroke is among the leading causes of morbidity and mortality in the United States. Carotid stenosis is the underlying pathology for 25% of an estimated 800,000 annual strokes. The prevalence of carotid disease is age dependent, with a prevalence of 0.5% after age 60 and up to 10% in the population older than 80 years. There is a direct correlation between the degree of carotid artery stenosis and the risk of ipsilateral stroke. The majority of cases of carotid stenosis are asymptomatic; however, symptomatic stroke treatment and lost productivity due to stroke account for an estimated annual cost of $41 billion. The devastation associated with ischemic stroke has led to medical, surgical, and interventional treatments for the prevention of ischemic stroke through the treatment of carotid occlusive disease.

Historically, treatment of carotid occlusive disease revolved around two therapies: medical and open surgical intervention. Initial medical interventions focused on improving overall cardiovascular health through blood pressure management and mitigating the risk of thromboembolism with antiplatelet therapy. While effective, this therapy did not address the mechanical obstruction inherent to carotid disease. Studies in the early 1990s demonstrated an unquestionable benefit to mechanical intervention in the form of open surgery. These prospective, randomized, controlled studies proved a combination of surgical carotid revascularization by means of carotid endarterectomy (CEA) and medical management were highly successful in reducing the incidence of stroke among patients with moderate to severe symptomatic carotid stenosis and among those with severe asymptomatic carotid stenosis. Thus CEA became the standard of care for surgical revascularization for carotid occlusive disease.

Since the 1990s there have been significant advances in the medical and technological treatment of carotid disease. Our understanding of platelet and lipid biology led to the development of new pharmacologic agents to inhibit both platelet function and the development of atherosclerosis, thereby reducing the risk of the thromboembolic pathology associated with carotid obstructive disease. These advances, in addition to advances in stent technology, permitted the development of a third means of treating carotid disease: carotid artery stenting (CAS). Initially, CAS evolved as an alternative treatment to CEA for “high-risk” patients. Because high-risk patients accounted for up to one-third of the patients undergoing CEA, CAS was initially investigated as an alternative to CEA. The ability to treat mechanical obstruction without requiring the use of general anesthesia, with a less invasive intervention, was an attractive alternative to CEA. Further, beyond high-risk patients, endovascular therapy provided a means of accessing carotid disease that was previously inaccessible secondary to patient anatomy, body habitus, prior irradiation, or prior neck surgery.

Evidence

There is irrefutable evidence that for certain patient populations, CEA offers an advantage over best medical treatment (BMT) alone. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) generated prospective, randomized data demonstrating that symptomatic patients with carotid stenosis greater than 70% and a perioperative stroke or death rate below 6% are best treated by CEA over BMT alone ^, The Veterans Affairs Cooperative Studies Program (VACSP) also found a beneficial effect of CEA when compared with BMT. The Asymptomatic Carotid Atherosclerosis Study (ACAS) proved asymptomatic patients with carotid stenosis of greater than 60% could benefit from CEA with a reduction in 5-year ipsilateral stroke risk, provided that their perioperative stroke or death rate was less than 3% and their modifiable risk factors were aggressively treated. Yet these key trials excluded patients deemed to be high risk for CEA. The initial indications for CAS were some of the key exclusion criteria from NASCET, VACSP, and ACAS, including restenosis after CEA, contralateral internal carotid artery (ICA) occlusion, previous neck irradiation, advanced age, renal failure, chronic obstructive pulmonary disease, and severe cardiopulmonary disease. The trial that led to US Food and Drug Administration approval for CAS was the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) study. The SAPPHIRE study demonstrated that CAS was at least equivalent to CEA in high-risk patients. SAPPHIRE 30-day myocardial infarction (MI), stroke, and death rates were 4.8% in the CAS arm versus 9.8% in the CEA arm ( P = .09). One-year MI, ipsilateral stroke, and death rates were 12.2% in CAS versus 20.1% in CEA ( P = .048). The 3-year incidence of stroke was 7% for both CAS and CEA. As CAS disseminated into wider practice, the question of whether CAS offered an alternative to CEA for a broader patient population arose.

Multiple studies attempted to answer this question; however, variability in study design, technology used, and patient selection made a comparison between CAS and CEA difficult. ^, Although a thorough discussion of the merits and flaws of these initial trials is beyond the scope of this chapter, one major point of contention revolves around the technology used in these studies. CAS, as a therapy that requires transgressing and manipulating a diseased carotid artery, as expected was associated with a higher perioperative risk of stroke when compared with CEA. Similarly, CEA is associated with a higher risk of perioperative MI secondary to the pervasive use of general anesthesia for the procedure. To mitigate the risks inherent to CAS, distal protection devices (DPDs) were engineered to diminish the perioperative risk of stroke associated with CAS. Of the initial trials, it’s worth noting that DPDs were used in 27% of the Stent Protected Angioplasty versus CEA (SPACE) treated cases, 72% of the International Carotid Stenting Study (ICSS), and 96% of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Of these trials, CREST showed the risk of the composite primary outcome of stroke, MI, or death did not differ significantly in the groups treated by CAS from those treated by CEA at 4- and 10-year follow-up. ^, This study, not unexpectedly, did find a higher risk of periprocedural stroke with stenting (4.1% vs. 2.3%, P = .01) and periprocedural MI with endarterectomy (1.1% vs. 2.3%, P = .03). The Carotid Angioplasty and Stenting Versus Endarterectomy in Asymptomatic Subjects Who Are at Standard Risk for Carotid Endarterectomy with Significant Extracranial Carotid Stenotic Disease (ACT I) trial recently demonstrated noninferiority of CAS, with no significant difference of stroke, MI, or death at 30 days and 1 year. These data are summarized in Table 62.1 .

Beyond DPDs, emerging technologies utilizing flow reversal and flow arrest during CAS are currently under evaluation, marking further prospective advances in endovascular therapy. Recent evidence in the ROADSTER trial evaluating flow reversal using a direct common carotid access technique in combination with flow reversal at the time of crossing the aneurysmal plaque demonstrated a periprocedural stroke rate of 1.3%, similar to that seen with CEA. Although these techniques are not yet fully prevalent in clinical practice, early small center results demonstrate a promising reduction in the rate of periprocedural infarction.

In parallel with advances in endovascular intervention, as previously discussed, medical therapy has progressed substantially in the past 20 years. The incidence of ischemic stroke continues to drop, calling into question the present validity of earlier trials. Carotid revascularization for primary prevention of stroke (CREST-2) is a double-randomized controlled clinical trial evaluating both CEA versus current BMT and CAS versus BMT ( ClinicalTrials.gov number, NCT02089217). Thus, as a practice, all patients with carotid disease in our institution are evaluated for trial participation and/or enrolled in ongoing clinical registries and trials.

Preoperative Evaluation and Management

Standard preoperative evaluation consists of radiologic evaluation of carotid stenosis and a neurologic assessment performed by a neurologist or neurosurgeon. Digital subtraction angiography remains the gold standard evaluation of carotid stenosis; however, the associated risk of stroke and cost of the procedure preclude its use as a primary modality. Computed tomographic angiography (CTA), magnetic resonance angiography (MRA), and carotid duplex ultrasonography have largely replaced angiography in clinical practice. ^, Imaging advances assessing the quality of associated plaque and risk for thromboembolism to better stratify those patients needing treatment are currently under investigation but not yet used routinely in clinical practice. ^,

After determining eligibility, elective and semielective patients are started on dual antiplatelet therapy (DAPT) of aspirin 325 mg and clopidogrel 75 mg 1 week prior to intervention. Some evidence suggests the combination of aspirin and clopidogrel decreases restenosis by inhibiting myointimal proliferation. ^{, ,} Next-day interventions, without time to fully load DAPT, are given 325 mg aspirin and 300 mg clopidogrel. For emergent cases, a variety of enteral and intravenous (or arterial) agents can be considered. During a procedure, a patient can be bolused with integrilin during the intervention and subsequently given PR 300 mg ASA and transitioned to an oral agent. It is not our practice to perform clopidogrel testing on patients prior to intervention. Further, despite evidence within the literature demonstrating that newer antiplatelet agents have increased antiplatelet activity and a similar safety profile, without the variability associated with clopidogrel, the cost of these on-patent medications often precludes their pervasive use within American practice. ^,

Preoperative laboratory results include hematocrit, hemoglobin, platelet count, white blood cell count, serum creatinine, prothrombin time, and activated partial prothrombin time are obtained within a week of intervention. Further, considering the underlying atherosclerotic pathology for these patients, cardiac evaluation with baseline 12-lead electrocardiogram is also performed. More in-depth cardiac or pulmonary evaluation is performed case by case, as deemed medically necessary. All patients have a baseline brain computed tomography or magnetic resonance imaging to document preexisting infarctions. On the day of the procedure, the patient’s National Institutes of Health Stroke Scale (NIHSS) is assessed and recorded.