BULgarian Carotid Artery Stenting versus Surgery Study (): Randomized single center trial Ivo Petrov, M. Konteva, H. Dimitrov, K. Kichukov Tokuda Hospital Sofia Cardiology Department
Background Carotid artery stenting (CAS) has shown in several trials no inferiority to the carotid endartherectomy (CEA) for patients with carotid stenosis. Still a debate persist about the safety and efficacy of CAS compared to CEA. This constant argument is substantially powered by the results of clinical trials that have lot of limitations : The low complication rate of CEA is based on ACAS, NASCET, ECST trials with highly selected study groups, low risk patients, high volume participating operators and institutions. After the promising for CAS results of the CAVATAS 1 and SAPPHIRE 2,3 trials, the intermediate results of SPACE 4 and the unsatisfactory results of EVA 3S shook the scientific community, but EVA 3S 5 had great limitations: vascular surgeon at least 25 endarterectomies performed in the year before enrollment. interventional physician at least 5 stenting procedures in the carotid artery performed altogether. Multiple therapeutic devices 5 types of stents and 7 types of EPD. The first procedures were performed without mandatory EPD with catastrophic results Only 85.4% of the pts had dual antiplatelet therapy post procedure. 1. CAVATAS Investigators. Endovascular versus surgical treatment (CAVATAS). Lancet. 2001; 357: 1729 1737 2. JS. Yadav, Protected Carotid Artery Stenting versus Endarterectomy in High Risk Patients. N Engl J Med, 2004, 351;15 3. Gurm HS, Yadav JS et allong Term Results of Carotid Stenting versus Endarterectomy in High Risk Patients N Engl J Med 358:1572, April 10, 2008 4. 30 day results from the SPACE trial. The Lancet 2006; 368:1239 1247 5. Jean Louis Mas et al. Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis. N Engl J Med 2006;355:1660 71.
Background Many of the randomized trials present a significant bias from the real clinical practice comparing highly selected populations The using of historic control groups leads to rough comparison between high risk CAS procedures vs low risk surgical procedures
The need for a real life study In the era of evidence based medicine there is a substantial need of not only randomized clinical trials with high selective criteria but trials that bring the real life situation into science. Such a trial should compare CAS and CEA not only in selected patients but also in broad range of risk asymptomatic/ symptomatic patients. We designed and conducted a prospective, randomized, single center trial comparing CAS to standard CEA in patients with asymptomatic and symptomatic carotid stenosis without selection criteria about the risk profile. Patients were enrolled using unified selection criteria and the enrollment ratio was designed to be 1:2 (CAS to CEA) for the first 50 patients and 1:1 afterwords.
The need for a real life study Endpoints Primary endpoint: Comparative periprocedural incidence of any nonfatal stroke, acute myocardial infarction (AMI), transitory ischemic attack (TIA), death (combined MAE) and stroke and death for a 3 year follow up Secondary end points: Comparison of length of hospital stay Comparison of CAS procedures with and without distal EPD Analysis of the restenosis in the CAS group
Patient randomization schedule
Study design Between February 2001 and December 2004 in a single clinical center 219 patients were randomly assigned to either CAS or CEA : 101 were treated with CAS and 118 with CEA. CEA was performed by two operators with more than 200 cases individual previous experience. CAS single operator with more than 100 CAS procedures previous experience. 4 types of EPD (EPI filterwire, Angioguard, Spider, Guardwire), 4 types of stents (1 BE: Palmaz and 3 SE: Protégé, Precise, X act) Patients baseline characteristics Index CAS n= 101 СЕА n= 118 n % n % Р Value Males 79 78.2 99 83.9 0.129 ns Age > 70 years 23 22.7 25 21.18 1.000 ns Mean age 62.47 ± 8.41 NA 63.94 ± 8.707 NA 0.206 ns Diabetics 29 28.7 39 33.0 0.870 ns Hypertension 95 94.05 108 91.5 1.000 ns Dyslipidemia 64 63.36 79 66.95 1.000 ns History of smoking 50 49.5 62 52.5 1.000 ns Arteriitis 2 1.9 1 0.8 1.000 ns
. Study design Baseline clinical characteristics Index CAS n= 101 СЕА n= 118 n % n % Multivessel involvement 78 77.22 83 70.3 ns CAD 69 68.3 71 60.1 ns Peripheral artery disease 16 15.8 18 15.2 ns Neurologically symptomatic 59 58.4 72 61.1 ns TIA 27 26.7 37 31.3 ns Ischaemic stroke 34 33.6 35 29.6 ns Neurologically asymptomatic 42 41.5 46 38.9 ns Subtotal occlusion 10 9.9 11 9.3 ns P value
Periprocedural results Entire population Index CAS n=101 CEA n=118 P value Ipsilateral stroke 2 2.0% 3 2.5% 1.000 ns AMI 1 1.0% 1 0.8% 1.000 ns Death 1 1.0% 1 0.8% 1.000 ns ТIA 7 6.9% 7 5.9% 0.788 ns МАЕ 9 8.9 % 12 10.2% 0.821 ns
Periprocedural results Patients age over 70 Index CAS n=23 CEA n=30 P Value Ipsilateral stroke 1 4.3% 2 6.7% 1.000 ns AMI 1 4.3% 0 0% 0.434 ns Death 1 4.3% 1 3.35% 1.000 ns МАЕ 6 26.1% 6 22.6% 0.743 ns ТIA 5 21.7% 3 10% 0.272 ns
Periprocedural results Diabetic patients Index CAS n=29 СЕА n=39 P Value Ipsilateral stroke 1 3.4% 1 2.6% 1.000 ns AMI 0 0% 1 2.6% 1.000 ns Death 0 0% 1 2.6% 1.000 ns МАЕ 4 13.8 % 4 10.3% 0.715 ns ТIA 3 10.3% 1 2.6% 0.305 ns
BULCASS Length of Hospital Stay Patient group Hospital stay (Days) P Value CAS n=100 3.94 ± 3.40 p< 0.005 9.50±4.91 CEA n= 117
CAS subanalysis. Early results EPD vs no EPD Index EPD n=94 W/o EPD n=7 р 0 % 2 Ipsilateral stroke 0 28.6 % 0.040 AMI 0 Death 0 ТIA 6 0 % 1 0 % 1 6.3 % 1 14.3 % 14.3 % 14.3 % 0.069 ns 0.069 ns 0.405 ns МАЕ 6 6.3 % 3 42.8 % 0.015
Late results 3 year follow up Index CAS n=100 CEA n=117 P Value Ipsilateral stroke 4 4.0% 5 4.2% 1.000 ns AMI 4 4.0% 5 4.2% 1.000 ns Death 6 6.0% 11 9.2% 0.450 ns МАЕ 9 9.0 % 16 13.6% 0.297 ns Restenosis 4 3.9 % 5 4.2 % 1.000 ns
Early procedural and late results after 3 year follow up
CAS subanalysis. Late results. SE vs BE stents Index Stent type Self exp. n= 83 Balloon exp. n= 14 n % n % р Ipsilateral stroke 2 2.4 2 14.3 0.098 ns Restenosis 1 1.2 3 21.4 0.009 Death 4 4.8 1 7.1 0.549 ns LМАЕ 6 7.2 2 14.3 0.325 ns
Conclusions In experienced hands and using appropriate materials, both methods CEA and CAS could be performed at low mortality and morbidity rate This study suggests that the incidence of nonfatal stroke, death, TIA and combined MAE following carotid stenting is statistically equivalent to carotid endartherectomy. The interventional carotid treatment is associated with a significantly shorter hospital stay. The preventive role of both methods regarding stroke rate are equivalent. The balloon expandable stents are not suitable for CAS, confirmed by other studies 1 The use of distal EPD during CAS is mandatory 1. Iyer SS, Roubin GS, Yadav Js et al: Extracranial Carotid artery stenting: balloon expandable versus self expanding stents. Circulation 1996; 94(Suppl I): 485
final remarks The study represents a real life situation without pre selection bias for either arm CAS or CEA based on low or high operative risk, symptomatic or asymptomatic carotid lesion. Limitations of the study Low number of the study population
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