ABC | Volume 111, Nº4, Octuber 2018

Review Article Oliveira et al Risk-benefit of carotid revascularization Arq Bras Cardiol. 2018; 111(4):618-625 taken into account in the design of the protocols of clinical trials involving CAS. In an attempt to standardize the group of operators, the EVA-3S study 8 included only interventionists with a minimum of 12 carotid angioplasties performed previously. The SPACE study 9 required a minimum of twenty and five previous procedures. Although most studies report the total volume of procedures performed by the operator, the few ones that specifically addressed this point were not able to show an association between the operator's prior experience and lower rates of complications. 36-38 The combined analysis of three large randomized trials (EVA-3S, SPACE and ICSS), published in 2012, 39 showed great differences in the incidence of death or stroke when the operators were stratified by annual volume of procedures. Procedures performed by operators with at least six carotid angioplasties per year had an incidence of stroke and death in 30 days of 5.1%, while the procedures performed by those with three or less, showed a 10.1% incidence. It is important to observe that all operators included in the analysis had already performed a minimum number of procedures, i.e., had already surpassed the learning curve. Unlike the annual volume, the total volume of carotid procedures performed during the life of the operator had no association with an increase of complications such as stroke and death, in concordance with other previously published studies. 40 Symptomatic patients revascularization – a time sensitive benefit The results of the main studies with symptomatic patients demonstrate that the greatest benefit of intervention occurs in the first weeks after the index event. 41-43 After the first 14 days, there is a rapid decrease in the benefit of the intervention, and more than 70% of the protective effect is seen within the first 30 days; after two years, the symptomatic patient presents the same risk level as the asymptomatic patient. 41-43 However, this recommendation has been poorly implemented with less than 20% undergoing revascularization within two weeks the onset of the stroke or TIA. 44 A Danish nationwide initiative was able to increase the percentage of CEA within the recommended timeframe from 13% in 2007 to 47% in 2010. 45 The evidence of the early procedure safeness is more robust for CEA than for CAS which has conflicting results in different studies. 46-48 Secondary prevention is indicated in cases of transient ischemic accident or small strokes, due to the high risk of intracranial hemorrhage when performing carotid intervention in the first few weeks after a major ischemic stroke and to the questionable clinical benefit in the long term. 49 Patient with asymptomatic severe carotid lesion The ACAS study, published in 1995, 5 showed that the adjusted risk of stroke and death associated with the intervention was 2.3%, with the endarterectomy preventing 59 cerebral vascular accidents in five years for every 1,000 procedures performed. Despite the very low risk as compared to that observed in practice and to those of the old pharmacological practices, 94% of the CEA were unnecessary. With an adjustment of the periprocedural risk to 0%, eighty‑two cerebral vascular accidents would be prevented for every thousand endarterectomies, but still 92% of the patients would be submitted to a procedure without benefits. The same principle can be applied to the 10-year results of the ACST which showed that, with a reduction of the periprocedural risk to 0%, 74 cerebral vascular accidents would be prevented for every thousand endarterectomies, meaning that 93% of the procedures would have been unnecessary. 17 The large clinical trials currently conducted have been limited to the comparison between carotid angioplasty and surgery. The lack of a clinical therapy group in the ACT I study, published in 2016, was strongly criticized. 50 The new editions of the studies SPACE, SPACE-2 (ISRCTN78592017), CREST and CREST-2 (NCT02089217) planned the inclusion of a third group in clinical therapy, but the SPACE-2 study was suspended by a low rate of inclusions. Presently, the CREST-2 trial has included more than 780 of the 2,480 patients referred. The current guidelines of the European Society of Cardiology for asymptomatic patients with severe lesions and a moderate surgical risk recommend endarterectomy (Class IIa) in the presence of clinical characteristics and/or imaging results suggestive of an increased risk of late ipsilateral stroke. Angioplasty should be considered (Class IIa) for patients with high risk for endarterectomy, provided that the rates of periprocedural death or stroke are < 3% and the patient's life expectancy is greater than five years, for any one of the groups. 31 The population with severe asymptomatic carotid stenosis is not homogeneous. Some lines of research try to identify patients with higher risk through more detailed imaging studies to locate markers of vulnerable plaques and microembolization. 51,52 That would allow a more cost‑effective carotid revascularization in patients currently classified as asymptomatic. Discussion The present review focuses on the primary and secondary prevention of ischemic stroke through carotid revascularization, which could impact 14% of all cerebral vascular accidents. 16 The first studies on this subject were published in the beginning of the 1990's. From the year 2000, studies have focused on the comparison between angioplasty and carotid endarterectomy, without the inclusion of a clinical therapy group for comparison. In this period, there has been significant improvement of clinical treatment and better control of risk factors. The use of acetylsalicylic acid for cardiovascular prevention was already routine decades before a decline in rates of cardiovascular events was observed, suggesting that other classes of drugs are responsible for this change. In the last decades, several studies have shown the impact of statins on cardiovascular outcomes, with a reduction in incidence of up to 50%. 26 The data reviewed in the present study show that, for a net benefit of the procedure, carotid intervention should only be performed in cases of a periprocedural risk of less than 6% in symptomatic patients or 3% in asymptomatic patients. A systematic review published in 2015 showed that carotid revascularization is more efficient in symptomatic patients but is associated to a higher incidence of death and stroke. In addition, the results did not show a trend to improved 622