Carotid Revascularization Endarterectomy vs. Stenting Trial - CREST
Current literature indicates that carotid artery stenting (CAS) is not superior to carotid endarterectomy (CEA), with a potentially higher risk of complications. Accordingly, CAS is currently reserved for high-risk patients, who are not good candidates for surgery. However, there has been a significant improvement in CAS and CEA techniques over the past few years. Therefore, the CREST study sought to compare outcomes between CAS and CEA in a contemporary population.
Contribution to the Literature: The CREST trial showed that CAS is associated with similar rates of periprocedural stroke, death, myocardial infarction (MI), and subsequent ipsilateral strokes up to 10 years compared with CEA in a contemporary population.
- Age >18 years
- Symptomatic patients with recent neurological events (TIA, amaurosis fugax, or non-disabling stroke) with an associated carotid stenosis ≥50% by angiography, ≥70% by ultrasound, or ≥70% by computed tomography angiography (CTA) or magnetic resonance angiography (MRA)
- Asymptomatic patients with no recent (in the last 6 months) neurological events referable to the study with artery and carotid stenosis (patients with symptoms beyond 180 days are considered asymptomatic) ≥60% by angiography or ≥70% by ultrasound or ≥80% by CTA or MRA
- Conditions that: 1) interfere with the evaluation of endpoints, 2) are known to interfere with the completion of CEA or CAS, or 3) affect the likelihood of survival for the study period (4 years)
- MI within 30 days
- Unstable angina
- Chronic atrial fibrillation and/or anticoagulation or episodic atrial fibrillation within the last 6 months
- Occurrence of any stroke, MI, or death during a 30-day periprocedural period
- Ipsilateral stroke during follow-up of up to 4 years
- Health-related quality of life
A total of 2,522 patients were randomized, of whom 1,271 were randomized to CAS and 1,251 to CEA. Of the total, 1,332 were symptomatic, and the rest were asymptomatic. The majority of patients had risk factors for cardiovascular disease, including diabetes (30%), hypertension (86%), dyslipidemia (84%), current smokers (26%), and prior coronary artery bypass grafting (21%). The majority of patients had ≥70% stenosis at the time of randomization (86%).
The primary endpoint of death, myocardial infarction (MI), or stroke at 30 days plus ipsilateral stroke up to 4 years was similar between the CAS and CEA arms (7.2% vs. 6.8%, hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.81-1.51, p = 0.51). Periprocedural all-cause mortality was also similar (0.7% vs. 0.3%, p = 0.18). Periprocedural strokes were higher in the CAS arm (4.1% vs. 2.3%, p = 0.01). However, the incidence of debilitating and major strokes was similar between the two arms (0.9% vs. 0.6%, p = 0.52). Minor strokes were more frequent in the CAS group (3.2% vs. 1.7%, p = 0.01). The incidence of periprocedural MI was significantly lower in the CAS arm, as compared with the CEA arm (1.1% vs. 2.3%, p = 0.03). Cranial nerve palsies were also more common in the CEA arm (0.3% vs. 4.7%, p < 0.0001). Results for the primary endpoint during the periprocedural period were similar for symptomatic (6.7% vs. 5.4%, p = 0.69) and asymptomatic (3.5% vs. 3.6%, p = 0.56) patients.
Long-term follow-up suggested that the incidence of ipsilateral stroke over 4 years of follow-up was similar between the two arms (2.0% vs. 2.4%, p = 0.85).
On 10-year follow-up, the primary endpoint for CAS vs. CEA was 11.8% vs. 9.9% (p = 0.51). No interaction was noted by symptomatic status. Postprocedural ipsilateral stroke was 6.9% vs. 5.6% for CAS vs. CEA (p = 0.96); major stroke was 2.7% vs. 1.1% for CAS vs. CEA (p = 0.2); and restenosis/repeat revascularization was 12.2% vs. 9.7% for CAS vs. CEA (p > 0.05).
Subgroup analyses suggested that there was no difference based on gender or prior stroke/transient ischemic attack (TIA) status. However, there seemed to be evidence of effect modification by age for the primary endpoint (p = 0.02), such that patients ≤69 years did better with CAS, whereas those ≥70 years did better with CEA. Moreover, the younger the patient, the greater the benefit with CAS, and conversely, the older the patient, the greater the benefit with CEA.
The results of the CREST trial indicate that CAS is associated with similar rates of periprocedural stroke, death, MI, and subsequent ipsilateral strokes up to 10 years, as compared with CEA in a contemporary population. This was true for both genders, and irrespective of the presence or absence of symptoms. The risk of periprocedural minor strokes is higher with CAS, whereas the risk of periprocedural MI is higher with CEA. Older patients derive more benefit from CEA, whereas younger patients derive more benefit from CAS.
These findings are very interesting, and are contrary to those noted in earlier trials such as SPACE, EVA-3S, and ICSS. To some extent, this could be a reflection of better contemporary medical management and evolving endovascular technology and experience.
In addition, all CAS operators in this trial underwent rigorous training and credentialing. It is left to be seen whether based on this study, the Centers for Medicare and Medicaid (CMS) will reconsider its current coverage decision regarding CAS, especially if performed by experienced operators.
Brott TG, Howard G, Roubin GS, et al., on behalf of the CREST Investigators. Long-Term Results of Stenting Versus Endarterectomy for Carotid-Artery Stenosis. N Engl J Med 2016;374:1021-31.
Brott TG, Hobson RW 2nd, Howard G, et al., on behalf of the CREST Investigators. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010;363:11-23.
Clinical Topics: Anticoagulation Management, Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Vascular Medicine, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Magnetic Resonance Imaging, Hypertension
Keywords: Amaurosis Fugax, Ischemic Attack, Transient, Follow-Up Studies, Credentialing, Extravehicular Activity, Ticlopidine, Carotid Arteries, Risk Factors, Dyslipidemias, Confidence Intervals, Medicare, Carotid Stenosis, Hypertension, Myocardial Infarction, Stroke, Cranial Nerve Diseases, Endarterectomy, Carotid, Medicaid, Heparin, Centers for Medicare and Medicaid Services (U.S.), Constriction, Pathologic, Stents, Coronary Artery Bypass, Magnetic Resonance Angiography, Diabetes Mellitus
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