Abstract
Evaluation of: Brott TG, Hobson RW 2nd, Howard G et al.; the CREST Investigators. Stenting versus endarterectomy for treatment of carotid-artery stenosis (CREST trial). N. Engl. J. Med. 363(1), 11–23 (2010).
Stroke has a high incidence and is associated with a dramatic degree of morbidity and mortality. Carotid stenosis is responsible for approximately 20% of strokes in all patient populations, and is especially prevalent in elderly patients. Therapies to decrease the risk of stroke are urgently warranted. The first established therapy was surgical endarterectomy. Over the last few years, however, carotid artery stenting has evolved as a less invasive approach. Hitherto, the paper under evaluation (the North American Carotid Revascularization Endarterectomy versus Stenting Trial [CREST]) is the largest and most important study comparing these two treatment modalitites. The study demonstrates comparable effectiveness for carotid stenting and carotid artertectomy to reduce the risk for future strokes.
Stroke is the third most common cause of death among adults in the USA and a leading cause of long-term disability. Carotid stenosis accounts for approximately 20% of strokes in the patient population and this proportion is even higher in elderly patients. Over the last few years, carotid artery stenting (CAS) has become an important alternative to carotid endarterectomy (CEA) Citation[1]. However, results of studies comparing CAS with CEA have been very controversial Citation[2,3]. In the context of this ongoing debate, the North American Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) represents a landmark study that attempted to provide more definite answers Citation[1].
Summary of methods & results
The CREST study was a large multicenter randomized controlled clinical trial with blinded end-point adjudication Citation[1]. A total of 2502 patients with carotid stenosis with (‘symptomatic’) or without previous stroke (‘asymptomatic’) were included in the study. This trial involved 108 centers in the USA and nine in Canada. Eligibility criteria were stenosis of 50% or more on angiography, 70% or more on ultrasonography, or 70% or more on computed tomographic angiography or magnetic resonance angiography if the stenosis on ultrasonography was 50–69%. Patients were randomized to either CAS or to surgical CEA. The primary end point of this trial was a composite of stroke, myocardial infarction or death from any cause during the periprocedural period or any ipsilateral stroke within 4 years after randomization. The patients were followed up for a median of 2.5 years. The study did not reveal a significant difference in rates of the primary end point between the stenting group and the endarterectomy group (7.2 and 6.8%, respectively; hazard ratio with stenting: 1.11; 95% CI: 0.81–1.51; p = 0.51). However, periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7 vs 0.3%; p = 0.18), for stroke (4.1 vs 2.3%; p = 0.01), and for myocardial infarction (1.1 vs 2.3%; p = 0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0 and 2.4%, respectively; p = 0.85).
Discussion
The CREST study authors conclude that carotid stenting performed by highly qualified surgeons and interventionists is effective and safe. The investigators found that stroke was more likely after CAS while myocardial infarction was more likely after CEA, but the effect on the quality of life was less significant than the effect of stroke. They appropriately state that low absolute risk of recurrent stroke suggests that CAS and CEA are clinically durable.
Expert commentary
The topic addressed by this study is highly important and has been controversially debated over the last decade. Stroke has a high incidence and is associated with a massive impact on mortality and on quality of life. This paper represents a landmark study in this field. It has been published very shortly after the publication of the second largest trial on this topic, the International Carotid Stenting Study (ICSS), which recruited 1713 patients with prior stroke and extracranial carotid artery stenosis of above 50% Citation[4]. The primary safety end point was the combined rate of any stroke, myocardial infarction or death within 30 days after treatment. The study revealed better outcomes for CEA with a hazard ratio of 1.73 (95% CI: 1.18–2.52; p = 0.004) for the primary end point. The study was smaller than the discussed CREST trial and like most preceding studies, the operators performing CAS were less experienced than the operators performing CEA. Furthermore, protection devices were not used in all patients.
As mentioned previously, the CREST trial is the largest study on this topic. In contrast to most previous studies, it provides long-term follow-up data. In general, the study was very carefully designed and included a lead-in phase to assure sufficient skills of the operators. Protection device use was compulsory. The end points were assessed in a blinded fashion by neurologists to reduce report bias. Approximately a dozen studies have already been published in this field but most of them were smaller and had methodological flaws limiting the validity of the results. Most of the studies involved experienced surgeons performing carotid endarterectomies and unexperienced interventionalists performing carotid stenting Citation[5]. Thus, the comparison was confounded. However, meta-analysis of all these trials prior to the CREST trial are in line with the discussed CREST trial and show that during the procedure, the risk of stroke and death is higher than with CEA. This increased risk is mainly driven by an increased risk for minor strokes Citation[5].
The CREST authors claim that their study shows comparable results for both interventions. However, the authors of CREST included periprocedural myocardial infarction in the primary composite end point, and it is debatable whether this is really meaningful. Myocardial infarction has less impact on the quality of life of patients than stroke (and obviously much less than death).
However, in the longer term both methods show comparable results in CREST as well as in the meta-analysis of all prior trials Citation[5]. In fact, CEA comes with a significantly increased risk for periprocedural infarction. Therefore, we need to carefully select optimal therapy for an individual patient based on their surgical risk (comorbidities and risk for myocardial infarction) and based on the carotid anatomy.
Current evidence, including the discussed CREST trial, suggests that carotid stenting for the primary or secondary prevention of stroke can be used as an alternative to CEA. CAS comes with some increased risk for periprocedural stroke and death while long-term outcomes appear to be similar and periprocedural myocardial infarction risk is lower. Until more data prove that ongoing technical progress will lead to further reduction of periprocedural stroke risk, stenting should be reserved for patients at higher surgical risk and with optimal vessel anatomy for a stenting approach.
Five-year view
When taking a closer look at the outcome of carotid stenting and CEA, early studies showed a dramatic superiority of CEA over carotid stenting. Over the past several years, the outcomes for both methods became more comparable, as illustrated by a cumulative meta-analysis Citation[5] and now with the CREST trial. This time effect is most likely related to improvements in equipment (e.g., protection devices and lower profile stents), technique as well as medical cotherapy. There is still an increased periprocedural risk for minor strokes with carotid stenting compared with the surgical approach. I am convinced that further improvements in equipment, especially in protection devices such as filters, will further decrease the periprocedural risk. Carotid stenting will be an appropriate alternative approach for treatment of carotid artery disease, especially in patients at higher surgical risk.
Key issues
• Stroke has a high burden of mortality and morbidity.
• Carotid artery stenosis is responsible for approximately 20% of strokes.
• Surgical carotid endarterectomy is the classical treatment for carotid stenosis; carotid stenting is an evolving alternative technique.
• While earlier studies suggested inferiority of this new technique, this most recent and largest published trial shows comparable results between the two treatment options.
Financial & competing interests disclosure
Pascal Meier is supported by a research fellowship grant from the Swiss National Science Foundation, the Schweizerische Stiftung fuer Medizinisch-Biologische Forschung SSMBS. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
References
- Brott TG, Hobson RW 2nd, Howard G et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N. Engl. J. Med.363(1), 11–23 (2010).
- Yadav JS, Roubin GS, Iyer S et al. Elective stenting of the extracranial carotid arteries. Circulation95(2), 376–381 (1997).
- Bonaldi G. Angioplasty and stenting of the cervical carotid bifurcation: report of a 4-year series. Neuroradiology44(2), 164–174 (2002).
- Ederle J, Dobson J, Featherstone RL et al. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet375(9719), 985–997 (2010).
- Meier P, Knapp G, Tamhane U, Chaturvedi S, Gurm HS. Short term and intermediate term comparison of endarterectomy versus stenting for carotid artery stenosis: systematic review and meta-analysis of randomised controlled clinical trials. Br. Med. J.340, c467 (2010).