Critical analysis of indications and outcomes of surgical treatment for carotid disease

O tratamento da doença carotídea tem ganhado enfoque nos últimos anos, principalmente com o advento da técnica endovascular, que defende o emprego da angioplastia e stent de carótida (CAS), principalmente em pacientes considerados de “alto risco” para a endarterectomia carotídea (ECA). Através da revisão bibliográfica, analisamos os resultados do tratamento da lesão carotídea em ambas as técnicas, realizando comentários embasados na experiência pessoal e nos dados da literatura, sobretudo nos pacientes de alto risco. Até o presente momento, não há evidência e justificativa para o emprego da CAS em larga escala nos pacientes com doença carotídea, inclusive nas situações de alto risco, tais como nos octogenários. No entanto, acreditamos que a CAS possa ser um coadjuvante no tratamento de pequeno número de pacientes com lesão carotídea (até 4% dos casos), como na presença de pescoço hostil, radioterapia prévia e alguns casos de estenose carotídea alta. Quando realizada com os cuidados técnicos necessários, a ECA ainda continua a melhor opção terapêutica aos doentes com lesão carotídea.


Introduction
Carotid revascularization for the treatment of brain ischemia -a transposition from the internal to the external carotid artery -was performed for the first time in Argentina, in 1951, by Carrea et al.However, it was published only in 1955. 1 Although others had tried, it was De Bakey who successfully performed the first carotid endarterectomy (CEA) in 1953.His seminal work, however, was only published in 1975. 2 A reason for great repercussion was the case reported by Eastcott et  al., who published what they believed to be the first case of brain revascularization -resection of the atheromatous segment followed by terminoterminal anastomosis of the common with the internal carotid artery, under moderate hypothermia, in 1954. 3In the 1950's and 1960's, that procedure was widely diffused, to the extent of reaching the 1970's with more than 100,000 annual procedures in the USA.That scenario made the American Society of Vascular Surgery hire an independent medical auditing led by the neurologist H. Barnett, who concluded that about 60% of carotid surgeries had questionable or inadequate indication.With the aim of defining indications and results of CEA, two studies were conducted, North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST), well consolidated trials that defined indication of carotid procedures. 4,5ter confirmation of good CEA outcomes in those studies, compared with the clinical treatment (patients submitted to control of risk factors and use of platelet antiaggregating agents), the number of surgeries grew again in the 1990's.
Over the past years, with the advent of the endovascular technique, carotid angioplasty and stenting (CAS) has been increasingly indicated.The industrial complex has encouraged comparative studies, with the aim of justifying use of this technique for the treatment of carotid disease, especially in patients characterized as "high risk," in whom there might be a competitive advantage in favor of this new technique.
There already are eight studies comparing both techniques: LEICESTER, WALLSTENT, CAVATAS, LEXINGTON I and II, SAPPHIRE, EVA-3S and SPACE.8][9][10][11][12][13] In Brazil, practice of carotid surgery has more than 40 years, and a survey has been published about indications and about who would indicate that procedure: neurologists, cardiologists or vascular surgeons. 14Increased interest on this theme is shown by the publication of more than 10 papers in Jornal Vascular Brasileiro, and an issue has recently received two editorials: one of them justifying indication of the endovascular technique 15 and another basically performing a description of comparative studies, with comments on both techniques by the author at the end of the paper. 16is analysis aims at describing comparative data between both techniques, based on facts taken from a wide literature review, associated with considerations, comments and positions about the treatment of atherosclerotic carotid disease.

Indications of carotid endarterectomy
It is worth stressing that CEA is a procedure that has been performed for more than 50 years.Therefore, there has been enough time to analyze its benefits and limitations in the short, medium and long term.It is likely that any other surgical procedure has been so much discussed and audited over the past years.
Considering the different criteria to measure the degree of stenosis by the studies NASCET and ESCT, the Carotid Endarterectomy Trialists Collaboration (CETC) analyzed the results of the three main studies in symptomatic patients, showing a maximum benefit in symptomatic patients with stenosis between 70-99% (NNT = 6, meaning that only six patients submitted to surgery would be needed to avoid a negative outcome -stroke). 19In addition, certain groups of patients have a greater benefit with CEA: males; presence of contralateral occlusion; aged over 75 years; hemispheric symptoms; irregular plaque; and associated intracranial disease. 21ny critics stress that such studies do not reliably illustrate CEA results in daily practice.In this context, it was demonstrated through the analysis of the American Medicare data that, from 1985 to 1996, rates of stroke and death were 3% in 61,273 procedures performed in 1985, and 1.6% in 108,275 procedures in 1996. 22In that same study, the authors also demonstrated that stroke and death rates were associated with number of procedures performed per surgeon -1.9% for surgeons with more than 50 annual procedures and 2.5% for surgeons with less than 20 annual surgeries.
With regard to studies involving asymptomatic individuals, the ACAS demonstrated benefits of the surgery in male patients without significant comorbidities, with carotid stenosis equal or higher than 60%. 17The ACST, published in 2004, basically demonstrated that CEA reduced risk of fatal stroke in half, and both men and women were benefited by the surgery. 19The clinical implications of those two studies were stressed by Naylor, from England: "men with asymptomatic stenosis between 60-99% and with good clinical conditions and aged less than 75 years are benefited by prophylactic CEA, and such benefit is smaller in women." 23xt, situations considered as high risk are presented, in which choice between both procedures can be proposed based on data published over the past 10 years.

Residual or recurrent stenosis
Residual stenosis, although rare, characterizes a form of patient undertreatment, since the atheromatous plaque was not completely removed.The previous surgeon maintained a portion of the distal plaque, or performed a plaque dissection in superficial section, inadequate for the surgery objective, i.e., complete removal of the lesion.An example of that can be seen in Figure 1.Arteriography represents the tissue lesion of a patient that had been submitted to CEA, around 30 days before, in another service.In this case, we identified presence of tissue lesion in the internal carotid artery, performing endarterectomy with complete removal of residual plaque (Figure 2).The patient had good postoperative course and is currently with 5 years of follow-up and no late complications.
Recurrent stenosis can be caused by myointimal hyperplasia or by recurrent atheromatous plaque.Myointimal hyperplasia is characterized by exuberant fibrous proliferation.It is usually early, commonly between 6 months and 2 years after the procedure, characterized by smooth superficial layer, with minimal potential of embolization.Diagnosis is generally performed by auscultation of carotid murmur and by color-flow Doppler ultrasound or angiographic tomography.Surgical treatment is rarely required, although this indication has been exaggerated over the past years.
Recurrent atheromatous plaque usually has late presentation (usually after 5 years of surgery).It can be located in the area previously submitted to endarterectomy, in the proximal portion of the common carotid or in the distal portion of arteriorrhaphy.This has been one of the indications for endovascular treatment, but it should be considered that, in recurrent arteriorrhaphy lesion, surgical indication can also be well supported when performed by an experienced surgeon, since the degree of technical demand is higher.
Personally, in cases of recurrent stenosis due to atheromatous plaque, we use conventional access, avoiding direct dissection of the distal portion of the internal carotid artery, before obtaining control of retrograde flow using a Fogarty catheter.That maneuver allows us to avoid exaggerated and more traumatic dissection in an area with fibrosis, which makes the procedure more difficult.If the late lesion is a stenosis of the common carotid artery ostium, we can use proximal endarterectomy using the RIFIFI technique (retrograde endarterectomy using Vollmar ring occluding the common carotid artery emergence with a Fogarty catheter). 24It demands more experience by surgeons.In the last 250 cases we treated, that technique was necessary in five patients (2%), who had proximal common carotid artery lesion.There were no deaths or strokes in the perioperative period (unpublished data).

Previous cervical radiation
The lesion usually has a difficult access due to diffuse fibrosis and longer extension, generating difficulties in dissection and procedure performance.It can cause a higher number of cranial nerve lesions.For some authors, CEA outcomes in patients previously submitted to radiotherapy have been encouraging, such as inexistent neurological morbidity perioperative mortality rates. 25,26wever, CAS can be considered the first option, although its medium-term outcomes are not well known.

Presence of kinking in the internal carotid artery
Existence of a hemodynamically significant and symptomatic kinking), usually associated with atheromatous plaque of the proximal internal carotid artery, can require treatment.Its anatomical characteristics may limit endovascular technique.However, kinking can be corrected using the technique of endarterectomy with eversion, since there is usually proximal atheromatous plaque and, after endarterectomy, reimplantation of the internal carotid artery at the bifurcation level, with or without resection of the redundant artery segment, has very good results. 27,28Figure 3 shows a perioperative image, and Figure 4 shows the control of a patient 10 years after the procedure, with excellent outcome.In our 250 most recent cases, there was presence of kinking in 40 patients (16%).Of these, there was one transient ischemic attack (2.5%) and one perioperative death (2.5%).

Distal stenosis
Presence of distal stenosis of the internal carotid artery is not a common situation, and it can be detected in less than 5% of cases submitted to surgery. 29It is being currently indicated for endovascular treatment, since CEA results in higher incidence of cranial nerve lesion. 30To avoid that problem, we have used conventional access and intraluminal control of reflux, using a Fogarty catheter placed in distal position.Thus, there are conditions of a high dissection of the plaque and its consequent removal, with good outcome.Other surgical maneuvers, such as section of the digastric muscle and mandibular subluxation, may also be needed. 30,31stal lesions can be an indication for endovascular treatment, especially if the surgeon has little experience with the conventional procedure.

Old age
Patients older than 80 years have been suggested as risk factor for the conventional technique, CAS being recommended in that situation. 32The literature, however, has demonstrated that such conduct is wrong, since exactly the opposite has been observed.4][35] This fact can be due to several factors, such as presence of more extensive atherosclerotic lesions, with higher calcification degree in the bifurcation, associated with presence of ulcers and thrombi.There may also be proximal ostial stenoses, which make catheter passage difficult, or ulcerated lesions at the aortic arch level, which facilitate mobilization of fragment of plaques or thrombi by passing catheters and devices used in carotid angioplasty.
As to the conventional technique, since the treatment is direct, the surgeon can adopt some cares that are essential and that benefit the patient.If performed with excellent technique, it can avoid intravascular manipulation, resulting in stroke and death percentages around 1.9-4.8%,[38][39] It can be concluded that, from the practical perspective, in patients aged 80 years or more, the endovascular treatment should be contraindicated, since the conventional treatment (carotid endarterectomy) has better short-and medium-term outcomes.

Contralateral occlusion
The treatment of carotid stenosis in patients with contralateral occlusion (CLO) has been stigmatized as a high-risk procedure.A citation from the results of the NASCET study has been wrongly used, showing an approximate 14% rate of perioperative morbidity and mortality in a restricted group of 21 patients. 42][43][44][45][46][47][48][49] By analyzing NASCET data, it is possible to observe some causes that might have been important for the poor outcomes in this group of patients.The sample of patients with CLO was small (n = 21) and the neurological events occurred in the immediate postoperative period.This is usually due to a technical problem more associated with the surgeon, and not to disease severity.An intraluminal shunt was not used in two out of three patients who progressed with stroke after the surgery, which could have been avoided if intraoperative brain protection had been used.We believe that use of shunt is a crucial issue in carotid surgery, especially for patients with CLO.Not using it because one thinks it is dangerous may characterize a form of undertreatment.In a recently published study, we used shunt in almost 90% of patients with CLO.There was one stroke (1.6%) and three deaths, two of them due to acute myocardial infarction (AMI) and another resulting from postoperative stroke (4.9%).One of the patients who had a fatal AMI was submitted to associated myocardial revascularization (MR). 48Samson et al., 45 through the analysis of 27 articles on carotid endarterectomy in patients with CLO, observed that occurrence of stroke in patients in whom the shunt was not used (6.2%) was practically the double than in patients in whom the device was routinely used (3%).
Another interesting aspect to obtain good outcomes in patients with CLO is medical team experience.Bonamigo et al. 48identified that, in studies reporting less than 50 patients submitted to surgery, mortality and stroke rates were 6.5 and 9.9%, respectively, whereas in studies reporting more than 50 patients, those rates were 1.6 and 4.1%, respectively.

Associated myocardial revascularization
Patient with carotid and coronary disease with indication of MR have also been considered as high risk. 50rough a compilation of outcomes in 49 studies about this theme, rates of postoperative stroke, AMI and death were 4.3, 2.2 and 4.2%, respectively, in a total of 4,788 patients studied. 51Naylor et al. 52 published a systematic review of 94 articles, finding stroke, AMI and death rates of 4.6, 3 and 4.6%, respectively.Similarly, Rizzo et al. 53 found stroke, AMI and death rates of 5.6, 3 and 4.8% in 1,815 patients analyzed.3][54][55] With those data, it is possible to conclude that CEA associated with MR can be performed with adequate results if the cardiologic status is reasonable and the carotid lesion is significant and symptomatic.In exceptional cases, such as MR due to unstable angina or extensive coronary lesion associated with critical carotid lesion with CLO, it is obvious that the percentage of stroke/death/AMI will be higher.

High-risk patients for carotid endarterectomy
Over the past years, many authors have indicated the endovascular treatment for patients characterized as high risk.The SAPPHIRE, published by Yadav et al. in 2004, was the study that insisted the most in that, justifying indication of the endovascular treatment with 30-day stroke and death rates of 4.8%, compared with 9.8% rates in the surgical group (p = 0.09). 11Opposed to that position, Mozes et al., 56 at Mayo Clinic, published a series of 323 cases with patients considered as high risk and, therefore, suitable for endovascular treatment as proposed by the SAPPHIRE study.Mozes et al., using the conventional technique, had stroke and death rates of only 1.4 and 0.3%, respectively.The results of the surgical group in the SAPPHIRE study and in other comparative studies show a significant difference between historic series of CEA and the results reported by such comparative studies, as shown in Table 4. [57][58][59] If one questioned that reference centers do not represent global experience, we could bring data from Medicare, published by Hsia et al., in which stroke/death rates were 3% in 1985 and 1.6% in 1996. 221][62] Gasparis et al. 60 defined high risk in two groups: physiological risk and anatomic risk.In the former, they included 80 patients older than 80 years, 11 with AMI over the past 6 months, 16 with heart failure, chronic pulmonary occlusive disease and 13 with serum creatinine levels above 3 mg/dL.In anatomic risk, they included 66 patients with contralateral occlusion, 29 cases of reoperations, three patients with previous radiotherapy and 53 with distal lesion. 60Those authors possibly published the best study to demonstrate the mystification created with the widespread use of the "high risk" classification.They were careful enough to offer the 560 low-risk patients the same cares provided to the group of 228 high-risk patient, namely patch in 86 and 84% of cases, internal shunt in 93 and 97% of cases and general anesthesia in 98% of cases.Thus, they had a very similar stroke and death rate, that is, 1.1% for the low-risk group and 1.3% for the so-called high-risk group.
It can be concluded that the high-risk factor, as reported and accepted by many, sometimes is more associated with how the procedure is performed than to the patient's comorbidity.

Limitations of the endovascular technique
Studies aiming at supporting indication of endovascular treatment are comparative, funded by the industry with the purpose of being approved by the Food and Drug Administration (FDA) for commercialization of devices in the USA.Since the FDA demands, at least, non inferiority to the results obtained with conventional technique, it is easy to understand how the study is designed and how patients are selected in the surgical branch.,63 By acting like that, the studies SAPPHIRE and SPACE showed very similar results, certainly due to reasons explained above. 11,13The EVA-3S study, funded by the French Department of Health and performed in university centers, showed extremely favorable results regarding endarterectomy (3.9% in the CEA group and 9.6% in the CAS group), the reason why the ethics committee determined its suspension, since the evidence had already been confirmed. 12other interesting aspect is identification of selection criteria of patients for CEA or CAS, proposed by Becquemin, a French surgeon experienced in both techniques. 64In Table 6, there are 11 indications for CEA and only three for CAS, showing that the anatomic aspects is also a limiting factor of using CAS.If this detail is not considered critically, it is almost certain that many endovascular procedures will not be concluded and, if so, they will have a high rate of complications after the procedure.Becquemin concluded the chapter claiming that: "There is neither evidence nor consensus regarding selection of patients for carotid angioplasty.Before choosing between surgery or angioplasty with stenting, procedure risks should be carefully examined, including general, local and neurological risks.In addition, risk of technical failure due to anatomic peculiarities should also be taken into account". 64elieve it is important to include in this text conclusions of a systematic review recently performed by Biasi et al. 65 Those authors published an important review about indications of CEA and CAS, focusing on prevention of brain embolization.After a long discussion of this theme, based on the analysis of classical studies, such as NASCET, ECST and ACAS, and studies comparing both techniques, such as CaRESS, 66 SAPPHIRE, 11 SPACE, 13 ARCHeR 67 and EVA-3S, 12 concluded by listing 10 recommendations or comments, as follows: The premise that surgical risk is higher in patients excluded from the NASCET and ACAS study or adequate for the ARCHER study has not been confirmed.
There is no accepted criterion to definitely identify high-risk patients for CEA.
Indications of CAS as an alternative for CEA in high-risk patients are questionable.
The definition of high-risk patients should not be considered as reasonable to abandon CEA in favor of CAS.
Due to the low risk associated with CEA, CAS should be restricted to studies of records or to randomized clinical trials (RCT).
If there is a high-risk group, it is small and restricted to recurrent stenosis, hostile neck due to radiotherapy and only corresponds to 4% of series.
The series discussed in this analysis show that high-risk patients can be submitted to CEA with stroke rates equivalent to those observed in low-risk patients.It is unlikely that CAS offers any improvement in risk of stroke, compared with CEA.
Patients older than 80 years have increased risk of stroke during CAS, but an acceptable risk for CEA.
Much care should be given to asymptomatic individuals with multiple risk factors, in whom a predictable long-term benefit by CEA can be markedly reduced by survival of only 5 years.
Patients who are really high risk have short life expectancy and are better treated without intervention.
The authors also studied risk of brain embolization by both techniques and concluded that risk of brain embolization using the endovascular technique is eight times more frequent than using carotid endarterectomy. 65at aspect had already been reported by other authors. 68,69Occurrence of early dementia was reported by Vermeer et al. 70 Even brain infarctions considered silent can be associated with a major cognitive decline and dementia, in the follow-up of patients submitted to endovascular treatment.

Conclusion
CEA is a well established procedure with good short-, medium-and long-term outcomes.It is still the predominant indication for most situations involving atherosclerotic carotid disease, presenting good outcomes, even in situations considered as high risk, as long as it is performed by an experienced and well trained surgeon.CAS may have a complementary role in the treatment of carotid disease, such as in cases of hostile neck due to previous radiotherapy and recurrent stenosis of a very distal lesion.Therefore, in our opinion, it is a procedure limited to a small number of patients (approximately 4% of cases).This issue is still polemical and obviously has many interpretations and criticisms.A thorough discussion of this theme, involving all related aspects (ethical, medical and economic) can and should be encouraged.The patient's interest should prevail and the best treatment must be provided.Finally, it is important to remember that "light can result from a thorough and open debate."