Prospective and comparative study between endarterectomy and stent angioplasty with cerebral protection in carotid atherosclerotic lesions: 30-day results
(Portuguese PDF version)

Eugênio Carlos de Almeida Tinoco,1 Luis Felipe da Silva,2 Bruno Baião Luquini,3 Rafael Campanha,4 Marcelo Nascimento,5 Luciana Horta6

1. Head, Vascular and Endovascular Surgery Service, Hospital São José do Avaí (HSJA), Itaperuna, RJ, Brazil.
2. Professor, Vascular Surgery, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
3. Chief of clinics, Vascular and Endovascular Surgery Service, HSJA, Itaperuna, RJ, Brazil.
4. Second-year resident, Vascular and Endovascular Surgery Service, HSJA, Itaperuna, RJ, Brazil.
5. First-year resident, Vascular and Endovascular Surgery Service, HSJA, Itaperuna, RJ, Brazil.
6. Second-year resident, General Surgery Service, HSJA, Itaperuna, RJ, Brazil.

Correspondence:
Eugênio Carlos de Almeida Tinoco
Rua Pastor Abelar Suzano de Siqueira, 305/603 - Cidade Nova
CEP 28300-000 - Itaperuna, RJ, Brazil
Tel./Fax: 55 22 3824.3507
E-mail: ecatinoco@globo.com

ABSTRACT

Objective: To comparatively analyze the 30-day results between endarterectomy and angioplasty using self-expandable stent and filter protection in the treatment of carotid bifurcation atherosclerotic lesions. The primary endpoint was to analyze stroke and death rate, as well hospitalization time.

Methods: Comparative and prospective study in 80 symptomatic and asymptomatic patients, with carotid bifurcation stenotic lesions greater than 60 and 70%, respectively. The patients were divided into two groups of 40 and assessed according to gender, age, associated comorbid conditions and smoking.

Results: The stroke and death rate was 5.0% for both techniques. There was only one case of transient ischemic attack (2.5%) in the endovascular group. Regarding hospitalization time, it was significantly lower in favor of the endovascular technique, with statistical significance (P < 0.002).

Conclusions: This study demonstrated a 5.0% incidence of stroke and death in 30 days considering both techniques. However, the endovascular group presented a statistically significant shorter hospitalization time than the endarterectomy group (P < 0.002).

Keywords: Carotid, endarterectomy, angioplasty.

J Vasc Bras. 2006;5(4):257-62

Article submitted October 19, 2006, accepted December 30, 2006.

 

INTRODUCTION

The ischemic stroke is the most common cause of neurological deficit in the elderly population, and the extracranial brain disease is responsible for approximately 20-30% of cases. Atherosclerosis obliterans is the main etiologic factor of these lesions.

Carotid endarterectomy (CE), throughout time, is the main therapeutic method in the treatment and prevention of ischemic strokes. The NASCET, ECST and ACAS studies demonstrated the superiority of the surgical over the clinical treatment in carotid stenoses. Based on data from those studies, the Ad Hoc Committee of American Heart Association established the indications in which endarterectomy should be performed.1-4 The main indications are symptomatic patients with stenosis ≥ 50% and asymptomatic patients with stenosis ≥ 60%. However, the surgical team should have morbidity and mortality lower than 6% in symptomatic patients and lower than 3% in asymptomatic patients.

The development of endovascular techniques and the possibility of treating carotid lesions led some authors to propose angioplasty in this territory. Initial results were not encouraging, but after stents were introduced there was improvement in results, placing stent angioplasty as a real alternative to endarterectomy.


STATISTICAL METHODOLOGY

The chi-square test was used to assess whether there was difference between groups regarding gender, hypertension, diabetes, heart disease, dyslipidemia, smoking and side in which the procedure was applied. In case of expected values lower than 5, Fisher's exact test was applied.

Mann-Whitney's test, which aims at comparing independent samples in relation to an interest measure, was used to compare the techniques as to age and hospitalization days. In addition, it is a nonparametric test, i.e., it is not based on mean and standard deviation, but on ranks (position of the individual in the sample) of measures.

All the results were considered significant for a significance probability lower then 5% (P < 0.05); therefore, there was at least 95% confidence in conclusions.


PATIENTS AND METHODS

From January 2004 to January 2006, 80 patients were prospectively treated at Hospital São José do Avaí (Itaperuna, RJ, Brazil), divided into two groups of 40 patients with primary atherosclerotic carotid lesion.

In both groups, the patients were treated by the same surgeon.

Endarterectomy was performed under loco-regional anesthesia, longitudinal incision in the neck and primary arteriotomy closure.

Angioplasty was performed through femoral approach, use of protection filter EPI/EZ (Boston Scientific) and Wallstent (Boston Scientific).

Inclusion criteria were patients older then 50 years independent of gender, symptomatic lesions greater then 60% and asymptomatic lesions greater than 70% detected by color-flow Doppler ultrasonography by the same examiner.

Exclusion criteria were total occlusion of the internal carotid artery; contralateral carotid occlusion; recent history (< 1 week) of acute myocardial infarction (AMI), transient ischemic attack (TIA) and/or stroke; history of any intervention in the carotid segment to be treated; non-atherosclerotic lesion (radiation or recurrent stenosis) and lesion of the common carotid ostium or high lesion of the internal carotid artery that spared the bifurcation.

The patients in both groups had the color-flow Doppler ultrasonography of carotid arteries as a preoperative examination performed by the same operator, as well as routine laboratory tests for these patients, that is, blood count, coagulogram, glucose serum dosage, urea, creatinine, sodium, potassium, cholesterol and triglycerides, besides electrocardiogram (ECG) and echocardiography for cardiologic evaluation. The patients who required a more judicious cardiologic evaluation were submitted to exercise test and, if necessary, coronary angiography. Endarterectomies were performed based on color-flow Doppler ultrasonography, whereas in the stent group an angiography was performed, consisting of a diagnostic and therapeutic examination, in case the lesion was confirmed.

From the pharmacological perspective, the patients in the surgical group underwent surgery taking acetylsalicylic acid 100 g/day and maintained indefinitely, whereas in the angioplasty group acetylsalicylic acid 100 g/day and ticlopidine 500 mg/day were used, starting 3 days before the procedure and maintaining both drugs for 30 days, besides further permanent use of acetylsalicylic acid 100 g/day.

In the group submitted to endovascular technique, 45% were female and 55% were male. In the group submitted to endarterectomy, 35% were female and 65% were male. However, there were no significant differences between both techniques regarding gender (P = 0.361). We observed that, in those submitted to angioplasty, mean age was 67.4 years (52-83), whereas in those submitted to endarterectomy it was 69.5 years (54-90), with P = 0.402, without significant differences between both groups.

Both techniques presented hypertension, diabetes mellitus, heart disease and dyslipidemia as their main comorbid conditions. However, there was no significant difference between both techniques regarding those diseases, as described next. Hypertension was observed in 85% of the patients submitted to angioplasty and in 80% of those submitted to endarterectomy (P = 0.556). As to incidence of diabetes mellitus, its presence was detected in 20% of the endovascular group and in 30% of those submitted to endarterectomy (P = 0.302). The incidence of heart disease was 25% in the endovascular group vs. 20% in those submitted to endarterectomy (P = 1.0). Dyslipidemia was found in 12.5% of the patients treated with angioplasty and in 5% of those submitted to endarterectomy (P = 0.432).

Smoking was present in 27.5% of patients submitted to both forms of treatment (P = 1.0).

As to the side in which the procedure was performed, the left side was affected in 60% of the patients in the endovascular group and in 42.5% of those treated with endarterectomy (P = 0.117).

With regard to preoperative symptoms, there was also balance between both techniques. Of the patients submitted to the endovascular technique, 70% were asymptomatic and 30% presented symptoms; of these, 41.7% presented TIA and 58.3% had stroke. In the endarterectomy group, 60% were asymptomatic and 40% had symptoms; of these, 50% presented TIA and 50% stroke (P = 0.587).

Endarterectomy was performed using longitudinal incision at the medial border of the sternocleidomastoid. Immediately after the incision, 100 U/kg endovenous heparin was administered. Special attention is drawn to the dissection of structures, avoiding sectioning without their recognition. In higher lesions, in which there is the need of more mobilization of the internal carotid segment, we performed the identification and repair of the hypoglossal nerve loop, avoiding its sharp movement. Clamping was performed, always starting by the internal, external and common carotid arteries. A longitudinal arteriotomy was performed, starting in the common carotid artery toward the internal carotid artery, extending up to 2 cm, unless in necessary cases. Once the whole plaque had been visualized, a conventional endarterectomy was performed, resecting the intimal and medial layers, exclusively leaving the adventitia. In cases of reduction in the patient's level of awareness, we used Javid's shunt under direct visualization of internal and common carotid lumens. At the end of endarterectomy, we proceeded to the distal fixation of the plaque using 7-0 prolene suture whenever necessary. Arteriotomy was traditionally closed using 6-0 prolene suture, always starting by the internal carotid artery and ending in the common carotid knot. Before ending the suture, an exhaustive washing of the arterial lumen with heparinized saline solution was performed, subsequently releasing arterial clamps in the following order: external, common and internal carotid arteries.

Angioplasty was performed in all cases using local anesthesia and puncture of the femoral artery. After the introduction of a 5 F sheath, 5,000 IU heparin were administered through the sheath. Next, we proceeded to the diagnostic angiography, which comprehends the study of carotid and cerebral arteries. After performing the diagnostic of the carotid lesion and the intention to treat it, we proceeded to catheterization of the external carotid artery and to the passage of an extra-rigid 0.0035" guide wire, to replace the 5 F sheath for a 6 F sheath measuring 90 cm in length (COOK, Bloomington, USA), which was introduced until short before the carotid bifurcation. At this moment, another dose of heparin was administered, maintaining the dosage of 100 IU/kg in total. The next step was releasing a protection filter EPI/EZ (Boston Scientific, USA), which should be always performed in a straight segment of the distal portion of the internal carotid artery, for a good insertion of the filter in the arterial wall, thus avoiding the passage of microemboli outside the filter. Next, we proceeded to the release of the Wallstent (10 x 24 mm) (Boston Scientific, USA). We did not perform predilatation, reserving it only to cases of extremely severe lesion. In these cases, we used a 4 x 20 mm coronary angioplasty balloon. After the stent was released, the anesthesiologist administered 0.05 mg/kg endovenous atropine, independent of the patient's heart rate. Postdilatation was performed with an angioplasty balloon ranging from 5.0-6.0 x 20 mm. After the expected result of angioplasty, we introduced the sheath to capture the protection filter, being careful not to completely pull the filter inside the sheath. We ended the procedure performing a carotid and cerebral angiography. We routinely used protamine sulfate to revert half the heparin dose. The sheath as removed after administration of protamine, with manual compression for 30 min at the puncture site and compressive bandage.

 

RESULTS

Use of shunt was necessary in 11 patients (27.5%), Javid's shunt being preferred (Table 1).

click hereTable 1 - Frequency of shunt use

Shunt
n%
No2972.5
Yes1127.5
Total40100.0

 

Clamping time varied between 20 and 45 min, with mean of 27.1 and median of 27 min.

The cerebral protection filter captured debris in only 11 (27.5%) of the 40 patients submitted to endovascular treatment.

Neurological complications (stroke) occurred in both groups, two patients (5.0%) in the endarterectomy group and one (2.5%) in the endovascular group. There was one death in the endovascular group as a consequence of MIA, and no deaths during the surgery. There was one (2.5%) case of TIA in the endovascular treatment (Tables 2 and 3).

click hereTable 2 - Evaluation of complications of the patients submitted to angioplasty (stroke and death)

VariablesFrequency
n%
Absent3895.0
Present25.0
Total40100.0

 

click hereTable 3 - Evaluation of complications of the patients submitted to endarterectomy (stroke and death)

VariablesFrequency
n%
Absent3895.0
Present25.0
Total40100.0

 

Comparing the techniques as to hospitalization days, there was statistical significance in the patients submitted to endarterectomy, who remained more days at the hospital than the patients submitted to endovascular treatment (Table 4).

click hereTable 4 - Descriptive and comparative measures of hospitalization days considering the technique used

Variable Descriptive measures
TechniquenMinimumMaximumMeanSDP
DaysStent401.08.02.01.40.002
Endart.401.09.02.81.9 
SD = standard deviation.



DISCUSSION

Randomized and comparative studies between both techniques were necessary to search for the best technique to be used in the patients. The largest study published to date is CAVATAS (Carotid and Vertebral Artery Transluminal Angioplasty Study).5 It is a multi-centered randomized study involving 560 patients in 24 centers. Of these, 504 patients with carotids stenosis indicated for surgical (253) or endovascular (251) treatment were randomized. Eighty-eight percent in the endovascular group and 91% in the surgical group presented symptoms over 6 months before the study. In the endovascular group, only 55 (22%) patients were treated with stent, whereas the rest was treated only with angioplasty. The incidence of stroke and death was 9.9% in endarterectomy and 10% in the endovascular group, an excessively high rate compared to the results obtained by NASCET and ECST.

Subsequently, some comparative studies were performed, but the high complication rate caused them to be terminated earlier. The two main examples are the Leicester study, in which, after 17 patients had been involved, five out of seven patients submitted to stent angioplasty without protection presented neurological deficit;6 and the Wallstent, a multi-centered randomized study that was terminated after recruiting 219 patients, when the incidence of stroke and death was 12.1% in the stent group without protection vs. 4.5% in the endarterectomy group.7 Contrasting those two studies, another study carried out in a single center in the USA randomized 104 patients with symptomatic stenosis > 70%, with no stroke in the surgical and endovascular group, one death in endarterectomy and none in the stent group.8 SAPPHIRE (Stenting with Protection in Patients at High Risk for Endarterectomy Study) is a multi-centered study comparing the efficacy of stent angioplasty with cerebral protection in patients of high surgical risk to endarterectomy. A total of 334 patients were recruited, 167 in the endovascular group and 159 in the surgical group. All patients were symptomatic with stenosis > 50%, or asymptomatic with stenosis > 80%. As to symptoms, 30 and 28% were symptomatic in the endovascular and surgical group, respectively. The primary objective of that study was to analyze the cumulative incidence of major cardiovascular events (stroke, MIA and death) in 30 days and 1 year. The complication rate in 30 days was 12.2% in the angioplasty group and 20.1% in the surgery group (P = 0.004 for non-inferiority and P = 0.053 for superiority).9

In a meta-analysis of those five studies, in a total of 1,157 randomized patients, there was no significant difference for stroke and death rate between both techniques, 8.6% in the endovascular group vs. 7.1% in the surgery group. Of the three studies providing information about the course of stroke, 6.0% of the patients treated with stent died or presented severe sequelae vs. 5% in the surgical group. When the MIA was included, there was no statistically significant difference between both groups as to incidence of death, stroke and MIA, 9.0% in both groups. With regard to nervous lesion, it was present in 7.2% in the surgery group and zero in the stent group (P < 0.00001).10

Despite the favorable results to the endovascular treatment demonstrated by SAPPHIRE, studies and records with use of stent and cerebral protection point to a result with relatively high complication rate. ARCHeR (Acculink for Revascularization in High Risk Patients) is a series of three multi-centered, prospective, nonrandomized and sequential studies, with distinct phases. The first phase involved 158 patients and did not use any cerebral protection device. In the second phase, the cerebral protection device ACCUNET (Guidant Corporation, Santa Clara, California, USA) was used, involving 278 patients. The third phase recruited 145 patients and used the same cerebral protection device, but with the fast exchange system. In all phases, the ACCULINK nitinol stent was used (Guidant Corporation, Santa Clara, California, USA). Death, stroke and MIA rate in 30 days was 8.3% (95% confidence interval, 6.2-10.8%), and death and stroke rate was 6.9% (95% confidence interval, 5-9.3%). The 30-day incidence of major or fatal stroke was 1.5%. There was no hemorrhagic stroke in this group. The incidence of ipsilateral stroke in 30 days and 1 year was 1.3%.11

Two studies recently published, EVA-3S12 and SPACE,13 could not demonstrate non-inferiority of the endovascular treatment results in relation to endarterectomy. They are prospective, randomized studies treating symptomatic patients with stenosis > 70%, according to ECST criteria. Both were suspended; the first due to the high complication rate in the angioplasty group (9.6%), and the second, despite the similar complication rate (6.84 vs. 6.34%), was not sufficient to confirm statistical non-inferiority. However, the main critiques to those studies are that only 27% of the patients used cerebral protection in EVA-3S and, in relation to eligibility of the centers that participated in the study, the learning curve of those who performed the procedure was questioned. Whereas the EVA-3S required the surgeon to have performed 12 stent angioplasties in carotid arteries or 35 stent angioplasties in the supra-aortic trunk, five in the carotid territory, the SPACE study required at least 25 successful angioplasties with or without stent in carotid arteries.

CARESS (Carotid Revascularization using Endarterectomy or Stenting System) is a clinical multi-centered, prospective and nonrandomized study, designed to determine the equivalence in stroke and death rate between stent angioplasty with cerebral protection and endarterectomy. The primary objective of phase I was to assess the incidence of stroke and death in 30 days. A total of 254 endarterectomies and stent angioplasties were performed in symptomatic (32%) and asymptomatic (68%) patients. Stroke and death rate in 30 days was 3.6% in the surgical group and 2.1% in the endovascular group. With regard to stroke, death and MIA rates, there was no statistical difference between both techniques, 4.4% in endarterectomy and 2.1% in angioplasty.14

The most expected study is CREST (Carotid Revascularization Endarterectomy versus Stent Trial), since it is supported by the National Institute of Neurological Disorders and Stroke and the National Institute of Health. The CREST study aims at comparing the efficacy of stent angioplasty with cerebral protection and endarterectomy. It is a randomized multi-centered study in symptomatic patients with stenotic lesions ≥ 50%. Its primary objectives are to assess the incidence of stroke, death and MIA in 30 days and ipsilateral stroke for a 4-year follow-up.15

 

CONCLUSIONS

This study demonstrated a 5% incidence of stroke and death in 30 days considering both techniques. However, regarding hospitalization time, there was a statistically significant reduction in favor of the endovascular technique.


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J Vasc Bras. - Official Publication of the Brazilian Society of Angiology and Vascular Surgery