Tabla 1. Comparison between American Heart Association (AHA) and European Society of Cardiology (ES...

Figura 1. Prevalence of survival patients from different conditions with neurological disability (in...

Tabla 2. CAVATAS Trial, 30 days and 1 year major adverse events

Tabla 3. SAPPHIRE Trial; 30 days and 1 year adverse events.

Figura 2. Risk of major cerebrovascular accident (CVA) in symptomatic and asymptomatic patients with...

Figura 3. CAVATAS Trial. Three years survival curves of death (A) and cerebrovascular accidents (B)....

Figura 4. SAPPHIRE Trial, Primary end-point at one year of follow-up.

Figura 5. SPACE Trial, death and stroke at 30 days in CE (Carotid Endarterectomy) vs CS (Carotid St...

Figura 6. EVA-3S Trial; randomization between CE (Carotid Endarterectomy) vs CS (Carotid Stenting) ...

Figura 7. EVA-3S Trial vs. the World: Influence of experience; 30 days death and stroke in carotid ...

Figura 8. CREST Trial Primary endpoint: Any periprocedural stroke, myocardial infarction, death or p...

Tabla 4. 30 days Results from Metanalisis from 11 randomized trials comparing CE with CA

Epidemiology

Cerebrovascular Accidents (CVA) are the third cause of mortality (150,000 per year) and the first cause of disability. In U.S.A. occurs one CVA per 45 seconds (800,000 per year), and with 150,000 deaths and three million survivors, it generates expenses for 58,8 billion dollars per year (Figure 1). Ischemia is the most frequent etiology (85%) and, of this, the atherosclerotic disease of the extra cranial internal carotid artery (ICA) is the responsible of 25% of the events. About 15 to 20% of all CVA are preceded by a transient ischemic attack (AIT). The risk of suffering a CVA after having an AIT is about 3 to 17%, and if it´s related to a carotid stenosis increases 20% (the incidence is higher between the first 15 days). This data clearly shows the magnitude of the problem.1

Randomized Trials that compared Medical Treatment and Carotid Endarterectomy

Historically, both medical treatment (MT) and carotid endarterectomy (CEA) were therapeutical resources used to prevent ischemic CVA in patients with atherosclerotic disease in ICA.

Asymptomatic carotid stenosis

From the three randomized clinical trials that compared MT and CEA in patient with asymptomatic carotid stenosis, both the Asymptomatic Carotid Atherosclerosis Study (ACAS, 1995)2 and the Asymptomatic Carotid Surgery Trial (ACST, 2004)3 the rates of CVA and death at five years showed statistically significant differences in favor of CEA (ACAS: MT 11.0% vs. CEA 5.1%; p=0.004 and ACST: MT 11.8% vs. CEA 6.4%; p<0.0001).

The other trial, the Veteran Administration Carotid Study (VACS, 1993),4 with a small sample size did not demonstrate statistically significant differences between MT (9.4%) vs. CEA (4.7%), p=0.06, at four years of follow up.

In relation of the three analyzed trials it must be taken in account that since the time they were made MT incorporate a very important arsenal of new drugs, such as statins, ACE inhibitors, ARB, new antiplatelet therapy (Clopidogrel, Prasugrel or Ticagrelor) combined to ASA, which had a strong impact in the prevention of ischemic CVA.

In that way, in the year 2009 Dr. Anne Abbot published in Stroke journal a systematic revision and analysis of current literature were she states that the medical treatment is the best intervention for the prevention of CVA in patients with asymptomatic carotid stenosis.5 In this paper she analyzed 11 trials (between 1985 and 2007) in Europe, U.S.A., Canada and Australia that included a total of 3724 asymptomatic patients with carotid stenosis and showed that, in the last 25 years, there were a significant decrease in annual rates of ipsilateral CVA and any CVA, attributable to the actual MT alone. This data was also inferior that the one presented in the ACAS study, CEA arm. Thereby there are numbers around 1% for ipsilateral CVA and 2% considering CVA or ipsilateral TIA. Also, this results demonstrated a significant statistically loss of benefit in the surgical treatment since 1980, 1990 and 2001 for the prevention of ipsilateral CVA, ipsilateral CVA/TIA and of any CVA/TIA, respectively. Additionally, MT results much more cost-effective than surgery: 3 to 8 times less expensive for the prevention of CVA, not forgetting that at the same time they are also preventing acute myocardial infarction and peripheral vascular disease.

In spite of this data published by Abbott, there is a sub-group of asymptomatic patients at higher risk of CVA than the overall population. In this sense, Madani recently published in Stroke the paper “High-Risk Asymptomatic Carotid Stenosis: Ulceration on 3-D Ultrasound vs. Transcranial Doppler Microemboli”, a prospective trial analyzing 253 asymptomatic patients with a carotid stenosis > 60%. They demonstrated that the presence of 3 or more ulcerations in the ultrasound was correlated with a significant higher rate of CVA (18.2% vs. 1.7%). Regarding the presence of microemboli in the transcreaneal doppler, the relation was about 20% with CVA vs. 1.7% in patients wihout microemboli.6 This patients could clearly have a benefit with the adition of a revascularization procedure to the MT.

Finally, an important point to consider; the loss of adherence to the MT in the “real world” is not a minor issue. It depends on many factors and it is difficult to resolve. Without any doubt, further randomized studies will be needed to analyze this particular population.

Let´s see what the guidelines can tell us about this. Actually, MT is considering the first option in asymptomatic patients with < 70% of carotid obstructions. In asymptomatic patients, with a stenosis between 70 and 99%, both American Heart Association (AHA) and European (ESC) guidelines7,8 established a class IIa, evidence level A for CE (Table 1) and sets that the morbi-mortality for the procedure in asymptomatic patients must be less than 3%.

Symptomatic Carotid Stenosis

Two major important clinical randomized trials compared MT with CE: the North American Symptomatic Carotid Endarterectomy Trial (NASCET, 1998)9 and the European Carotid Surgery Trial (ECST, 1998).10 Both trials demonstrated a benefit of CEA compared with MT in the significant reduction of major ipsilateral CVA rates (NASCET: MT 26% vs. CEA 9%; p<0.001 and="" ecst:="" mt="" 20="" 6="" vs="" cea="" 8="" p="0.0001)." both="" the="" american="" european="" guidelines="" span="">7,8 recommend the use of CEA in asymptomatic patients with 70 to 99% carotid stenosis: Class I, evidence level A (Table 1). And for the indication of CEA in symptomatic patients with 50 to 69% of stenosis there are discrepancies: AHA7 guidelines shows a class I, evidence level B and for ESC8 there is a class IIa, evidence level A (Table 1). In all cases they establish that the morbi-mortality of the procedure in symptomatic patients must be less than 6%.

From the evidence of the analyzed studies arises that the benefit of CEA over MT in relation of major CVA in much more overwhelming in symptomatic patients with carotid stenosis (Figure 2).

Randomized Trials and Meta-analysis that Compared Endarterectomy with Carotid Angioplasty

As a new therapeutically option, Carotid Angioplasty (CA) was first used more than 15 years ago for the prevention of ischemic CVA.

There are numerous non randomized trials and registries published from important centers and authors with national and international recognized experience as well as several randomized trials that compared CEA with CA.11

The “Carotid and Vertebral Artery Transluminal Angioplasty Study” (CAVATAS),12 was the first multi-centric randomized trial (22 centers from Europe, Australia and Canada) that included 504 patients (251 patients for each group) with symptomatic carotid disease. No significant differences were shown between both groups in the combined final end point of death or CVA at 30 days (10%) and 3 years (14%) (Figure 3 and Table 2). In the surgical group there was a higher rate of cranial nerves paralysis (CEA 8.7% vs. CA 0%; p<0.0001), as well as hematoma at the puncture site (inguinal or cervical) that required surgery or extended hospitalization (CEA 7% vs. CA 1%; p<0.0015). The restenosis rate at 1 year was assessed by ultrasound and showed to be higher in CA group (18%) than CEA (5%), p <0.001. notably="" there="" was="" no="" cerebral="" protection="" system="" used="" and="" the="" rate="" of="" stent="" implantation="" only="" 26="" span=""> (Table 2).

The “Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy” (SAPPHIRE),13 was the second multicentric trial (29 centers from USA) that included 334 patients, symptomatic with obstructions ≥ 50% and asymptomatic patients with obstructions ≥ 80%, assessed by angiography, with high risk criteria for surgery and they were randomized and assigned to each group. Remarkably, the majority of patients in the study were asymptomatic (CA 70.1% and CEA 72.3%), and together, surgeons and interventionists should accomplished the minimal standards required by a multidisciplinary committee of the study. The primary end point was death, CVA or acute myocardial infarction (AMI) at 30 days plus ispilateral CVA or death of neurological cause between 31 days and 1 year, and it was of 11.9% in CA group and 19.9% in CEA group (p=0.04 for non-inferiority and p=0.05 for superiority) (Figure 4 and Table 3). The peri-procedural cumulative incidence of death, CVA or AMI (between 30 days) was also lower in the CA group (4.4% vs. 9.9%, p=0.06) (Table 3). Nevertheless, the rate of CVA and death were similar in both groups, at 30 days (3.6% vs. 3.1%) as well as at 1 and 3 years, and the difference shown was attributable to the AMI excess in CEA group (6.6% vs. 1.9%, p=0.04) (Table 3).

At one year the rate of paralysis of the cranial nerves was higher in the CEA group (5.3% vs. 0%; p=0.003). The results at 3 years of the SAPPHIRE trial were published in 2008 with the data of 78% of the patients. The secondary pre-specified final end-point (primary end point plus death or ipsilateral CVA between 1 and 3 years) showed no statistically significant differences (CA 24.6% vs. CEA 26.9%; p=0.71).14

Accordingly to the SAPPHIRE trial, FDA approved the use of CA in symptomatic patients with internal carotid stenosis >70% and high surgical risk.

The largest randomized, multi-center and non-inferiority trials that compared CA vs. CEA were published in the year 2006. The “Stent-Protected Angioplasty vs. Carotid Endarterectomy in Symptomatic Patients” (SPACE)15 and the French trial “Endarterectomy versus Stenting in Patients with Symptomatic severe Carotid Stenosis (EVA 3S).16 The first one was done in 35 centers from Germany, Austria and Switzerland and included 1200 symptomatic patients to either CA (605) vs CE (595) groups. Only 27% of the patients received cerebral protection. The primary end point was ipsilateral CVA (ischemic or hemorrhagic or both) or death of any cause, since randomization to 30 days post procedure, and occurred in 41 patients of CA group (6.84%) and 37 patients from CEA group (6.34%) (Figure 5). The absolute difference between both treatments was of 0.51% (p=0.09 for non-inferiority). Nevertheless, the incidence of death, global CVA, non-fatal ipsi-lateral ischemic CVA, disabling CVA and non-fatal ipsilateral intra-cerebral bleeding didn´t show significantly differences between treatment groups. In a subgroups analysis of male patients under 75 years old, there were non-significant differences between CA and CEA (absolute risk difference of 0.04% and 0.02%, respectively). In contrast, there were major risk between elderly (3.5%) and women (1.7%) in CA group. Finally, it must be underline that, even though the SPACE trial do not met the end point for non-inferiority of CA compared to CEA, difference between both groups was of only 4 events in almost 600 patients treated in each group.

The French study (EVA 3S) also compared CA vs. CEA in symptomatic patients. They use cerebral protection in 92% of patients from CA group.16 The primary end-point was the incidence of any CVA or death in the first 30 days after the procedure. It was organized to include 872 patients to reach 80% of statistical power necessary to determine if CA was non-inferior than CEA but was ended prematurely after the inclusion of 527 patients for safety reasons. The rate of CVA and death was 9.6% in CA group and 3.9% in CEA group (p=0.01) (Figure 6). There was non-significant differences at 30 days in death (CA 0.8% vs. CEA 1.2%), major CVA (CA 2.7% vs. CEA 0.4%), minor CVA (CA 6.1% vs. CEA 3%) and non-disabling CVA or death (CA 3.4% vs. CEA 1.5%). There was a significant difference in favor of CA in the incidence of cranial nerves paralysis (CA 0.1% vs. CEA 7.7%, p<0.001). The main criticism of this study was the poor criteria used in the process of interventionist´s selection: 12 CA or at least 35 procedures with stents in supra-aortic trunks, with a minimum of 5 CA. There were centers with their interventionists supervised until the accomplished the necessary training. Opposed to that, the requirements for the vascular surgeons were stricter: At least 25 carotid endarterectomies in the previous year to patient inclusion. It is legitimate to conclude that, being CA an operator dependent procedure, the lack of appropriate training negatively conditioned the outcome of the CA group as we can see in Figure 7. Reinforcing this analysis, if we compared data from the CA arm of the last two trials (SPACE and EVA 3S), both published in 2006, the cerebral protection used in the first one was of 27% meanwhile in the last it reached 92% and, despite of this the rates of global CVA or death at 30 days was 6.8% in SPACE and 9.6% in EVA 3S. (The higher since CAVATAS trial published in 2001) (Figure 7). In October of 2008 the Lancet Neurology published the EVA 3S trial at 4 years (17). The outcomes were influence by the high rate of peri-procedural events of the trial, as the final end point at 4 years included the events from the 30 first days. The incidence of CVA or death in the 30 days after the treatment plus non related to the procedure ispilateral CVA at 4 years was 11.1% for CA vs 6.2% for the CEA, HR 1.97; p=0.03.

The last two major randomized and multicenter trials were published in 2010, the “International Carotid Stenting Study” (ICSS)18 and the “Stenting vs Endarterectomy for Treatment of Carotid Artery Stenosis” (CREST).19

The ICSS was done in 50 centers from Europe, Australia, New Zealand and Canada and included 1713 patients with symptomatic carotid stenosis. They used cerebral protection in 72% of patients of CA group. A safety provisional analysis at 120 days composed with the incidence of CVA or AMI at 120 days favored CEA 5.2 vs. CA 8.5% (p=0.006). Nevertheless, no significant differences were shown when they consider rate of death or disabling CVA: CEA with 27 events (3.2%) and CA with 34 events (4.0%), p=0.34, and the number of disabling CVA was identical. Clearly the effect observed in the safety analysis at 120 days, with an increment of 3% risk in CA group was mainly due to the higher number of non-disabling CVA in this group. The incidence of cranial nerves paralysis was much higher in CEA group (5.28% vs 0.12%; p<0.0001) and there were few AMI cases in both groups (CEA 3 vs. CA 4). Finally, the subgroup analysis in this trial did not show risk differences between groups, either in female or patients younger than 70 years old.

The CREST trial was done in 108 centers from USA and 9 from Canada and included 2502 patients with severe carotid stenosis and 47% of them, asymptomatic.19 Cerebral protection was used in 96.1% of patients in the CA group. The follow-up median was of 2.5 years and there were non-significant differences at 4 years in the final end-point: global CVA, AMI or death in the peri-procedural period or ipsilateral CVA during the 4 years of follow-up (CA group 7.2% vs. 6.8% in CEA group; p=0.51) (Figure 8).

As other previous studies, the incidence of global peri-procedural CVA was significantly higher in CA group (4.1% vs. 2.3%;p=0.01), due mostly to the higher rate of minor ipsilateral CVA, meanwhile the incidence of AMI was significantly less in CA group (1.1% vs. 2.3%; p=0.03). As ICSS and SPACE trials showed, there was also an increment in the risk with CA in elderly patients. On the other hand, CREST trial showed better results in the peri-procedural outcome than all the randomized trials published until now, either in CA or CEA.

At last, in 2010 a meta-analysis that included 11 randomized and control trials (4792 patients) that compared CEA with CA was published (Table 4).20 This trial showed that the risk of death and peri-procedural CVA was significantly lower in CEA group (5.4% vs. 7.3%; p=0.025) driven by lesser risk of CVA with CEA (4.2% vs. 5.7%; p=0.049, respectively) (Table 4). However the risk of death (CEA 1.4% vs. CA 1.2%; p=0.727) and the composite of death and disabling CVA (CEA 2.9% vs. CA 3.8%; p=0.09) did not differ between groups. On the other hand, the risk of peri-procedural AMI and lesion of the cranial nerves was significantly higher in CEA group (2.6% vs. 0.9%; p=0.036 and 7.5% vs. 0.45%; p<0.001, respectively) (Table 4). The mean follow-up (1 to 4 years) didn´t show statistically differences in CVA or death (p=0.314). The authors concluded that CEA showed superiority over CA at short term, less non-disabling CVA or minor CVA, although that difference disappeared at follow-up. At the same time they underline the excess of peri-procedural AMI and lesion of cranial nerves in CEA group.

Non Randomized Trials, Registries and Post Marketing Studies:

In the literature there are a many publications about CA, and even though there are no randomized trials or meta-analysis, they provide interesting data from the “real world”. There are single centers or multi-centric registries and post market studies.

In 1998, A. Mathur, G. Roubin, et al. published in Circulation an important trial about stroke predictors in CA. The “Predictors of Stroke Complicating Carotid Artery Stenting”21 included 231 patients with very high risk (71% with severe coronary disease, 39% with bilateral carotid disease, 12% with contralateral carotid occlusion, 39% with previous endarterectomy, 24% with ulcerative plaques and 32% with calcified lesions). Only 14% of the treated patients had eligibility criteria for the NASCET trial and the peri-procedural risk was of 2.7%. The incidence of complications at 30 days was: major stroke 0.7% and minor stroke 6.2%. The independent predictors of stroke were: 1. Advance age (p=0.006) and 2. Multiple and long lesions (p=0.006).

In the year 2000, M Wholey and cols published “Global Experience in Cervical Carotid Artery Stent Placement”,22 an important multicenter survey that included 36 centers from Europe, North and South America and Asia. They reported 5210 procedures in 4757 patients, 5327 stents with a technical success of 98.4% and a low rate of complications at 30 days: global death 1.22%, TIA 2.8%, major CVA 1.5%, minor CVA 2.7% and death plus CVA, 6.3%. At six months the restenosis rate by ultrasound (more than 50% of residual stenosis) was 2.27%.

These two mention trials are only a small sample of the great amount of published trials, non-randomized, and that had been an important support in the field of CA.

As to “post market” studies, they are done in USA and Europe with companies support in an early stage after the beginning of products commercialization; still they have a Clinical Events Adjudication Committee. Since 2004, the FDA approval of different carotid stents and cerebral protection systems were founded based in data from randomized clinical trials and data from research of devices in pre-clinical phases (IDE, “Investigational Device Expemtion”); several studies were done under this methodology.

The “Protected carotid stenting in high surgical risk patients (ARCHeR)” was a prospective, multicenter and one arm trial that analyzed carotid stenting with cerebral protection in patients with high surgical risk, symptomatics with more than 50% of internal carotid artery obstruction or patients without symptoms and more than 80% of stenosis.23 The composite primary end-point (death, CVA or AMI in the first 30 days after procedural plus ipsilateral CVA at one year) was 9.6% (less than 14.4% of the control historical comparator of CEA) (p<0.001 for="" non-inferiority="" also="" the="" rate="" of="" death="" cva="" or="" ami="" at="" 30="" days="" was="" 8="" 3="" meanwhile="" 6="" 9="" from="" 32="" 23="" were="" minor="" and="" 12="" have="" total="" recovery="" according="" to="" nih="" stroke="" scale="" revascularization="" culprit="" lesion="" tlr="" 24="" months="" 2="" span="">

Finally, the trials CAPTURE,24 EXACT and CAPTURE 2 among others, were “post-market” multicenter trials that contribute with good data about stroke incidence and the relation with variables such as age (> or < of 80 years) and the patient´s clinical status (symptomatic or asymptomatic).

Conclusions

I would like to conclude remarking the elements that, I consider, are crucial at the time of the election for the best strategy to treat stenosis of the internal carotid artery.

1. For patients with high surgical risk, CA is the method of choice.

2. For the treatment of patients with symptoms and moderate or mild surgical risk the experience and results of the procedural medical team has to be considered. It must take into account that CA demonstrated the same rate of major CVA compared with CEA, but higher non-disabling minor CVA, and that the CEA has higher AMI and cranial nerves lesions.

3. In very elderly patients, CEA has less CVA than CA.

4. The CA should still diminish the rate of peri-procedural events, especially TIA and non-disabling CVA. For this we must work jointly with the industry, sharing our experience to develop newer and better devices that could help us to improve the safety and efficacy of our procedures (catheters, guides, stents, protection systems, and others)

1. Thom T, Haase N, Rosamond W et al. Heart disease and stroke statistics--2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006 Feb14;113(6):e85-151. Epub 2006 Jan 11.

2. Walker MD, Marler JR, Goldstein M et al Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995 May 10;273(18):1421-8.

3. Halliday A, Mansfield A, Marro J et al. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004 May 8;363(9420):1491-502.

4. Hobson RW, Weiss DG, Fields WS et al and the Veterans Affairs Cooperative Study Group Efficacy of Carotid Endarterectomy for Asymptomatic Carotid Stenosis. N Engl J Med 1993; 328:221-227.

5. Abbott Anne L. Medical (Nonsurgical) Intervention Alone Is Now Best for Prevention of Stroke Associated With Asymptomatic Severe Carotid Stenosis: Results of a Systematic Review and Analysis. Stroke. 2009;40:e573-e583.

6. Madani A, Beletsky V, Tamayo A, Munoz C, Spence JD. High-Risk Asymptomatic Carotid Stenosis: Ulceration on 3-D Ultrasound vs. Transcranial Doppler Microemboli. Neurology. 2011;77:744-750.

7. Brott TG, Halperin JL, Abbara S et al. ASA /ACCF /AHA / AANN/ AANS/ ACR ASNR/ CNS /SAIP/ SCAI/ SIR/ SNIS/ SVM/ SVS. Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease Circulation 2011, 124:e54-e130.

8. Tendera M, Aboyans V, Bartelink ML et al. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases. European Heart Journal (2011) 32, 2851–2906.

9. Barnett HJ, Taylor DW, Eliasziw M et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med. 1998 Nov 12; 339(20):1415-25.

10. Eurpean Carotid Surgery Trialists Collaborative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet. 1998 May 9; 351(9113):1379-87.

11. Rodríguez AE, Fernández M, Peyregne E et al. Non Surgical Revascularization of Carotid Arteries. Role of PTA. Journal of Am Coll Cardiol 1995, 796-1.

12. Cavatas investigators. Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial. Lancet. 2001 Jun 2;357(9270):1729-37.

13. Yadav JS, Wholey MH, Kuntz RE et al. Protected Carotid-Artery Stenting versus Endarterectomy in High-Risk Patients. N Engl J Med 2004; 351:1493-1501

14. Gurm HS, Yadav JS, Fayad P et al. Long-Term Results of Carotid Stenting versus Endarterectomy in High-Risk Patients. N Engl J Med 2008; 358:1572-1578.

15. Ringleb PA, Allenberg J, Brückmann H et al. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet. 2006 Oct 7;368(9543):1239-47.

16. Mas JL, Chatellier G, Beyssen B et al. for the EVA-3S Investigators. M Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis. N Engl J Med 2006; 355:1660-1671.

17. Mas JL, Trinquart L, Leys D et al. for the EVA-3S Investigators. Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA 3S) trial: results up to 4 years from a randomized, multicentre trial. The Lancet Neurol 2008; 7:885-92.

18. 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. Lancet. 2010 Mar 20;375(9719):985-97.

19. Brott TG, Hobson II RW, Howard G et al. for the CREST Investigators. Stenting versus Endarterectomy for Treatment of Carotid-Artery Stenosis. N Engl J Med 2010; 363:11-23.

20. Meier P, Knapp G, Tamhane U et al. Short term and intermediate term comparison of endarterectomy versus stenting for carotid artery stenosis: systematic review and meta-analysis of randomised controlled clinical trials. BMJ. 2010; Feb 12;340:c467.

21. Athur A, Roubin GS et al. Predictors of Stroke Complicating Carotid M. Artery Stenting. Circulation 1998;97:1239-1245.

22. Wholey MH, Wholey M, Mathias K, Roubin GS et al. Global Experience in Cervical Carotid Artery Stent Placement. Catheterization and Cardiovascular Interventions. 2000; 50:160-167.

23. Gray WA, Hopkins N, Yadav S et al. Protected carotid stenting in high-surgical-risk patients: The ARCHeR results. J Vasc Surg 2006;44:258-69.

24. ray WA, Yadav S, Verta P et al. The CAPTURE Registry: Predictors G of Carotid Artery Stenting With Embolic Protection for High Surgical Risk Patients in the Early Post- Appr

    Translated by: A. Matías Rodríguez-Granillo.

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State of the art for the revascularization treatment of the extra craneal internal carotid artery. Carotid angioplasty role in light of randomized trials

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