A multisite randomized controlled trial comparing carotid endarterectomy with implantation of a carotid artery stent has shown the more invasive surgical procedure to be the safer and more effective – at least in the short term.

The International Carotid Stenting Study (ICSS), which enrolled 1,713 patients between 2001 and 2008, all with symptomatic atheromatous carotid artery stenosis, showed endarterectomy to be associated with lower rates of disabling and nondisabling stroke, myocardial infarction, and death within 30 days of the procedure, according to findings published Feb. 26 in The Lancet (Lancet 2010 Feb. 26 [doi:10.1016/S0140-6736(10)60239-5]).

In a related, blinded study on a subgroup of the same patients published the same day online in the Lancet Neurology, researchers used magnetic resonance imaging (MRI) to assess the rate of nondisabling ischemic brain injury soon after treatment in both the stent and endarterectomy groups. They found that half of the stent patients had at least one new ischemic lesion, compared with only 17% of those who underwent carotid endarterectomy. In addition, the incidence of lesions was even more pronounced when special protective filters were used during stenting (Lancet Neurol. 2010 Feb. 26 [doi:10.1016/S1474-4422(10)70057-0]).

The ICSS will continue to monitor patients until 2012, after which the longer-term safety of the procedures can be better compared, according Dr. Martin M. Brown, who was study leader for the findings reported in The Lancet.

“The interest in the long term is to see how well stenting protects from recurrent stroke,” he said in an interview. “There were more strokes caused by treatment in the stenting arm, but most of the high risk is during the procedure. But if you get away without a complication during the procedure, does it protect you in the long run? There are still lots of analyses we haven’t done yet.”

Dr. Brown, of University College and the National Hospital for Neurology and Neurosurgery, both in London, and his colleagues randomly assigned 855 patients to stenting and 858 to carotid endarterectomy. Three patients dropped out almost immediately; of the remainder, a smaller number underwent the assigned procedure (828 in the stenting group, 821 in the endarterectomy group). The intention-to-treat groups were assessed at 120 days after enrollment whether or not they had yet been treated, in part to gauge the health risk presented by delays in treatment. All of the treated patients were followed up 30 days after their procedures.

The risk of stroke, myocardial infarction, or death was higher with stenting than with open-neck surgery (8.5% vs.5.2%, respectively) within the first 120 days after randomization, and within 30 days of treatment (7.4% vs. 4.0%).

Within 30 days of treatment more nondisabling strokes occurred in the stenting group (36 vs.11), whereas the rate of disabling stroke or death did not differ as significantly (26 vs.18).

The incidence of one serious adverse effect – cranial nerve palsy – was much higher after 30 days in the group that had undergone open-neck surgery, compared with stenting (45 vs. 1).

In the MRI arm of the study (published in Lancet Neurology), participating clinicians used stents from a range of manufacturers during the trial, without finding clear differences in results. However, the researchers found that the proportion of patients with postprocedure lesions was higher when filter-type cerebral protection devices – designed expressly to prevent embolisms that can lead to lesions – had been used during stenting.

The MRI arm, led by Dr. Leo H. Bonati and colleagues at University Hospital Basel, Switzerland, was set up to provide an objective picture of the incidence of ischemic brain injury following both procedures. In it, 231 patients (124 in the stenting arm and 107 in the endarterectomy arm) received MRI before and after treatment. A total of 62 (50%) of 124 patients in the stenting group and 18 (17%) of 107 patients in the endarterectomy group had at least one new lesion detected on scans done the day after treatment.

In the patients who were treated at hospitals where cerebral protection devices were used, 37 (73%) of 51 in the stenting group had at least one new lesion on posttreatment scans, whereas in those treated at hospitals where unprotected stenting was used, 25 (34%) of 73 patients in the stenting group evidenced new lesions.

Dr. Brown said he suspected that the protection devices might have contributed to embolisms that resulted in lesions, but that better studies were needed. “It’s not as robust a comparison as a randomized controlled trial. It’s possible they could have been used only on high-risk patients.”

He said that he hoped the significance of the lesions themselves would become clearer toward the end of the study. “We want to follow everybody for at least 5 years. The anxiety is that patients with these little areas of damage could be more likely to get dementia later. We will be measuring for this.”

Of contributing investigators to ICSS and the authors on the MRI study, two reported conflicts of interest. One had received a research grant from W.L. Gore and had consultancy agreements with Gore and Boston Scientific. Another had consultancy agreements with CR Bard and Gore.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

一项比较颈动脉内膜切除术与颈动脉支架植入术的多中心随机对照试验表明，虽然颈动脉内膜切除术的手术创伤更大，但至少从短期来看，该手术更加安全，也更加有效。

 

《柳叶刀》(The Lancet) 2月26日发表的一篇文章显示，这项名为“国际颈动脉支架研究”(ICSS)的试验于2001~2008年共募集患者1,713例，所有患者均患有症状性颈动脉粥样硬化性狭窄。试验结果表明，在接受动脉内膜切除术的患者中，术后30天内致残性和非致残性卒中、心肌梗死和死亡的发生率都更低(Lancet 2010 Feb. 26 [doi:10.1016/S0140-6736(10)60239-5])。

 

《柳叶刀神经病学》(Lancet Neurology)也于同一天在线刊载了与之相关的另一项研究，这是在ICSS患者亚组中开展的一项盲法试验。研究者采用磁共振成像技术(MRI)来评价支架组和动脉内膜切除组治疗后即刻非致残性缺血性脑损伤的发生率。结果显示，支架组一半的患者都至少有1个新发缺血灶，而接受颈动脉内膜切除术的患者仅17%出现了新发缺血灶。此外，若在支架植入术中采用了特殊的保护滤网，缺血灶的发生率甚至更高(Lancet Neurol. 2010 Feb. 26 [doi:10.1016/S1474-4422(10)70057-0])。

 

《柳叶刀》上刊载的那项试验的主要研究者Martin M. Brown 博士表示，ICSS将继续对患者进行监测直到2012年，之后再对两种手术的长期安全性进行比较。

 

Brown 博士在采访中说：“开展长期试验是为了观察支架植入术对复发性卒中的预防效果如何。支架组因治疗导致的卒中事件更多，但高危情况大多出现在术中。不过如果术中没有出现并发症，那么从长期来看是否能一直发挥保护作用？目前仍有许多方面的分析都尚未开展。”

 

英国伦敦大学学院和国立神经病学和神经外科医院的Brown 博士及其同事将患者随机分组，855例接受支架植入术，858例接受颈动脉内膜切除术。其中3例患者几乎立即退出试验；在剩余的患者中，部分患者接受了试验所分配的手术(支架组828例，动脉内膜切除组821例)。入组试验后120天，在意向性治疗人群中评价受试者是否已接受了治疗，目的之一是评估治疗延迟对健康风险的影响。术后30天对所有接受了治疗的受试者进行随访。

 

随机分组后前120天内(8.5%对5.2%)以及术后30天内(7.4%对4.0%)，支架组患者发生卒中、心肌梗死或死亡的风险高于接受开颈手术的患者。

 

术后30天内，支架组患者发生的非致残性卒中事件更多(36对11)，但致残性卒中或死亡的发生率无显著差异(26对18)。

 

在接受了开颈手术的患者中，术后30天内严重不良反应——颅神经麻痹的发生率明显高于支架组(45对1)。

 

在该试验的MRI组中(发表于《柳叶刀神经病学》)，参与研究的临床医生在试验中采用了多个厂家生产的支架产品，结果显示各种产品之间无明显差异。但研究者发现，若在支架植入术中采用了滤网式脑保护装置(专门用于预防可能形成缺血灶的脑栓塞)，术后出现缺血灶的患者比例反而更高。

 

该MRI组试验是由瑞士巴塞尔大学医院的Leo H. Bonati博士及其同事领导开展的，旨在从客观上反映两种手术后缺血性脑损伤的发生率。共有231例患者(支架组124例，动脉内膜切除组107例)术前术后都进行了MRI检查。在支架组的这124例中有62例(50%)、动脉内膜切除组的107例中有18例(17%)术后当天MRI扫描至少发现了1个新发缺血灶。

 

支架组有51例患者是在采用了脑保护装置的医院接受的治疗，其中37例(73%)术后扫描至少发现了1个新发缺血灶，而在采用非保护性支架的医院中，支架组的73例患者仅有25例(34%)出现了新发缺血灶。

 

Brown博士说，他怀疑这类保护装置可能导致了形成缺血灶的脑栓塞，但尚需开展进一步的试验来证实这一猜测。“这种对照研究的证据力度不及随机对照试验。有可能只对高危患者使用了该保护装置。”

 

Brown博士说，他希望到试验结束时这些缺血灶本身的意义会变得更加明显。“我们计划对每例患者至少随访5年。令人担忧的是脑损伤区域很小的患者之后出现痴呆的可能性更大。我们将对此进行评价。”

 

在ICSS试验的研究者以及MRI试验的作者中，有两名作出了利益冲突声明。1名声明接受了WL Gore公司提供的研究经费，并与Gore和Boston Scientific公司签署了顾问协议。另1名则与CR Bard和Gore公司签署了顾问协议。

 

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