Stroke is one of the major causes of morbidity and mortality in the United States. While myriad processes can cause strokes, carotid artery disease is responsible for approximately one third of strokes. Given a clear relation between the degree of carotid stenosis and the risk of ipsilateral stroke,1,2 carotid revascularization in the form of carotid endarterectomy (CEA) has been highly successful in reducing the incidence of stroke in patients with moderate-to-severe symptomatic carotid stenosis,1 as well as in those with severe asymptomatic stenosis.3 While CEA has been highly effective in the setting of clinical trials at reducing the long-term risk of stroke, it carries with it the early hazard of perioperative stroke and death, along with other complications such as periprocedural myocardial infarctions, cranial nerve palsies, and wound infections.
It was realized that the hazard of death and stroke associated with CEA was much higher in the community than had been recognized in clinical trials.4,5 Furthermore, the procedure was increasingly being performed in patients who were deemed to be at greater surgical risk owing to anatomical reasons or secondary to medical comorbidities, a cohort that had been excluded from the clinical trials.
In parallel with the development of percutaneous coronary interventions, there was a concerted effort to develop a percutaneous technique to treat carotid stenosis. The recognition of embolism as an obligate hazard at every step of the procedure prompted the development of emboli-protection devices (EPDs) that have subsequently made the procedure safer and more appealing.6 The improved safety of carotid stenting with the availability of EPDs and self-expanding stents has made endovascular treatment of carotid stenosis a viable alternative to CEA. The recently published Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial directly compared carotid artery stenting (CAS) with CEA in patients deemed to be at high risk secondary to difficult anatomy or medical comorbidities.7
Patients and methods
The trial enrolled patients across 29 centers. Each patient had to be evaluated by a team comprised of a neurologist, an interventionalist, and a vascular surgeon or a neurosurgeon. All members had to agree on the need for revascularization before a patient could be enrolled into the trial. Following this, the patient was randomly assigned to CAS or CEA if the surgeon and the interventionalist concurred that revascularization could be successfully carried out with either technique. Patients deemed to be at high risk for CEA by the local surgeon but in whom CAS was judged feasible by the interventionalist were enrolled in a stent registry. Conversely, patients deemed suitable for only surgery were enrolled in a CEA registry.
Inclusion criteria mandated the presence of one or more high-risk criteria and either a symptomatic stenosis that was greater than 50% or a greater than 80% asymptomatic stenosis. The high-risk criteria included the presence of at least one of the following: significant cardiac disease (congestive heart failure, abnormal stress test, or the need for open heart surgery), severe pulmonary disease, contralateral carotid occlusion, contralateral laryngeal nerve palsy, recurrent stenosis after CEA, previous radical neck surgery or radiation therapy to the neck, or age older than 80 years.
Patients with any of the following were excluded: stroke within the previous 48 hours, presence of intraluminal thrombus, total occlusion, arterial disease precluding the use of catheter-based techniques, large intracranial aneurysm, need for three or more stents, a bleeding diathesis, planned percutaneous or surgical intervention within 30 days, life expectancy of under 1 year, and ostial lesion of the common carotid artery or brachiocephalic artery.
All patients received aspirin and were given therapeutic doses of heparin during the procedure. CEA was performed as per the surgeon’s favored technique. Patients in the CAS arm were pretreated with clopidogrel (Plavix) and continued this agent for 2 to 4 weeks after the procedure. All patients received a self-expanding nitinol stent (Smart or Precise, Cordis) with an EPD (AngioGuard, Cordis). The AngioGuard is a 0.014 guidewire with an expandable filter basket with a pore size of 100 µm.
The trial had a noninferiority design with the primary end point of the trial being the cumulative incidence of death, stroke, or myocardial infarction within 30 days after the procedure or death or ipsilateral stroke between 31 days and 1 year. The secondary end points included target-vessel revascularization (TVR) at 1 year, cranial nerve palsy, and complications at the surgical site or vascular access site.
The trial enrolled 747 patients, of whom 334 patients were randomly assigned to CEA or CAS. Of the 413 patients not randomized, the overwhelming majority (406) underwent stenting, while seven were followed in the CEA registry. The baseline characteristics of the patients were similar in both arms, except for a higher prevalence of coronary artery disease in patients in the CAS arm. An intention-to-treat analysis demonstrated non-inferiority of CAS versus CEA with no statistically significant difference in the incidence of major adverse events between the two groups (Figure 1). When the patients actually treated were compared, the CAS arm had a significantly lower incidence of the composite end point (12% versus 20.1%, P = .048). The incidence of cranial nerve palsy and TVR was significantly lower in the CAS arm (Figure 2). The average length of hospitalization was significantly shorter in patients receiving CAS (1.84 days versus 2.85 days, P = .002). The benefits of CAS over CEA were seen in both symptomatic and asymptomatic patients. The incidence of bleeding in the two arms was similar.
The SAPPHIRE study demonstrated the noninferiority of the less invasive strategy of CAS with EPD compared with CEA in patients deemed to be at high risk for complications. The benefits of CAS were evident in both symptomatic and asymptomatic patients and were achieved without any increase in major periprocedural complications in either group. Further, the incidence of cranial nerve palsies and restenosis was significantly lower in the CAS arm. This study thus validates the approach of using CAS with EPD in patients at high risk for complications with CEA. Compared with CEA, this strategy achieves the goal of carotid revascularization with a similar (or lesser) hazard of major complications and a marked reduction in minor complications. This low risk of periprocedural complications and a similar long-term outcome establishes CAS with EPD as a viable strategy in this challenging population. Further studies are warranted to assess this exciting approach in low-risk patients.