取栓术治疗缺血性卒中的疗效尚未被证实

国际卒中大会上公布的MR RESCUE研究显示，在治疗前进行神经影像学检查以识别良好半暗带模式的大血管前循环缺血性卒中患者中，不管影像学检查结果如何，取栓术和标准药物治疗的临床结局都相似(N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1212793])。

在这项研究中，华盛顿乔治敦大学医学中心的Chelsea Kidwell博士及其同事假设CT或MRI可识别具有良好半暗带模式的、从取栓术治疗中获益不同的患者。良好半暗带模式定义为预测梗死核心≤90 ml且危险区域内的预测梗死组织≤70%。患者在大血管前循环卒中发生8 h内接受治疗。在2004~2011年招募的127例患者中，118例完全符合纳入标准。患者的平均年龄为65.5%，美国国立卫生研究院卒中量表中位评分为17。总体而言，37%的患者接受静脉组织型纤溶酶原激活剂(TPA)治疗，80%的患者接受了MRI影像学检查。至腹股沟穿刺的中位时间为6.2 h。

Chelsea Kidwell博士

结果显示，4%的患者发生症状性出血，21%的患者死亡。90天改良Rankin量表(mRS)评分的转变分析显示，治疗与半暗带模式之间无显著关联。取栓术组和标准治疗组具有良好半暗带模式的患者的平均mRS分别为3.9和3.4，无良好半暗带模式的患者的平均mRS分别为4.0和4.4(P=0.14)。因此，半暗带影像学检查不能识别从血管内治疗中获益不同的急性缺血性卒中患者。在所有患者中，取栓术组和标准治疗组的90天平均mRS相似(3.9 vs. 3.9；P=0.99)。

Kidwell博士表示，未来需开展进一步随机对照研究，以全面检验通过半暗带影像学检查选择患者的假说及新一代支架取栓器的临床疗效。

随刊述评

在随刊述评中，南卡罗莱纳医科大学神经科学科的Marc Chimowitz博士表示，MR RESCUE研究在招募方面遇到困难，这是因为在美国食品药品管理局(FDA)批准器械并且联邦医疗保险(Medicare)为这些手术提供补偿后，血管内治疗的应用变得广泛并且许多治疗急性卒中的医生认为从此找到了答案(N. Engl. J. Med. 2013 [doi:10.1056/NEJMe1215730])。

Ralph L. Sacco博士

美国心脏协会前主席Ralph Sacco博士在接受采访时指出，仍需要对更多的患者进行研究，以明确哪些患者从血管内治疗中获益最大。静脉TPA治疗越早，预后越佳，这点同样适用于血管内治疗，但需记住的是，半暗带影像学检查会增加时间。取栓术是一种需要广泛技术和高深专业知识才能开展的治疗方式。上述研究观察到静脉TPA的疗效基本等同于取栓术，虽然这一结果可能对取栓术支持者和器械生产商而言是个坏消息，但对大众而言或许是个好消息。

对于这些评论，研究者Kidwell博士表示，先进的神经影像学检查和血管内治疗日后还是会扮演重要角色，这有待于对新的支架取栓器进行进一步研究。

MR RESCUE研究获美国国立神经障碍和卒中研究所资助。研究中所用的导管和器械由Concentric Medical公司提供。7位研究者为加州大学员工，是Merci取栓器的专利持有者。Chimowitz博士声明从美国国立卫生研究院获得研究支持。Sacco博士声明无经济利益冲突。

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By: PATRICE WENDLING, Internal Medicine News Digital Network

Patients with large-vessel, anterior circulation ischemic stroke who underwent pretreatment neuroimaging to identify favorable penumbral patterns had similar clinical outcomes after treatment with either embolectomy or standard medical care regardless of the imaging results in the MR RESCUE trial.

"MR RESCUE underscores the importance of confirming hypotheses in randomized, controlled trials prior to implementing treatment approaches in clinical practice," co-primary investigator Dr. Chelsea Kidwell said during a late-breaking plenary session at the International Stroke Conference.

Possible reasons for the results are low recanalization rates with less-effective, first-generation devices (Merci Retriever or Penumbra System), the introduction of two imaging modalities, and the potential for favorable outcomes in penumbral patients regardless of treatment due to sufficient perfusion through collateral vessels. Another possibility is that the penumbral imaging selection hypothesis is flawed as currently conceived, she said.

The MR RESCUE (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy) investigators hypothesized that CT or MRI would identify patients with a favorable penumbral pattern – defined as a predicted infarct core of 90 mL or less and 70% or less of the predicted infarct tissue within the at-risk region – who would differentially benefit from embolectomy. Patients were treated within 8 hours of onset of large-vessel, anterior circulation strokes. Embolectomy is particularly attractive in these cases as intravenous tissue plasminogen activator (TPA) often is not effective on these large, frequently disabling clots.

There was no significant interaction, however, between treatment assignment and penumbral pattern by shift analysis of the 90-day modified Rankin Scale (mRS) score, reported Dr. Kidwell, professor of neurology at Georgetown University Medical Center in Washington. The mean mRS scores in patients with a favorable penumbral pattern were 3.9 with embolectomy and 3.4 with standard care, and 4.0 and 4.4, respectively, among patients without a favorable penumbral pattern (P = .14).

"As such, the trial failed to demonstrate that penumbral imaging identifies patients who will differentially benefit from endovascular therapy for acute ischemic stroke," she said.

Among all patients, mean modified Rankin scores at 90 days were similar between embolectomy and standard care (3.9 vs. 3.9; P = .99).

"Further randomized, controlled trials of new-generation devices are needed to test the full spectrum of the penumbral imaging selection hypothesis and the clinical efficacy of new-generation stent-retriever devices," she said.

That may be easier said than done, despite the lack of randomized, controlled trial data proving the benefit of penumbral imaging selection or recanalization with embolectomy.

In an editorial (N. Engl. J. Med. 2013 [doi:10.1056/NEJMe1215730]) published online with the MR RESCUE results (N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1212793]), Dr. Marc Chimowitz with the neurosciences department at Medical University of South Carolina, Charleston, points out that recruitment to the IMS (Interventional Management of Stroke) III and MR RESCUE trials was difficult "because once the Food and Drug Administration approved the devices and Medicare provided reimbursement for these procedures, endovascular treatment became widespread and many physicians who were treating patients with acute stroke felt that the ‘answer was in.’ Therefore, treatment equipoise was lost."

In all, 127 patients were enrolled between 2004 and 2011, of which 118 were fully eligible. Their mean age was 65.5 years and median National Institutes of Health Stroke Scale score was 17. Overall, 37% received intravenous TPA, and 80% underwent imaging with MRI.

Symptomatic hemorrhage occurred in 4% and 21% died, Dr. Kidwell said. The mean time to groin puncture was 6.2 hours.
 
"All of this means that we still need to put more and more patients in research protocols to better figure out who will benefit the most from endovascular therapy," American Heart Association past-president Dr. Ralph Sacco, chair of neurology at the University of Miami, said in an interview. "It has been shown now, including the subanalysis from IMS III, that the earlier you recanalize the better, and so we need to be still thinking about time windows. Just like with IV [intravenous] TPA, the earlier we treat, the better. Well, with endovascular therapy that may be true as well and you have to remember that sometimes penumbral imaging adds time."

Although embolectomy proponents and device manufacturers may see the results as a setback, another take was expressed by an audience member, who described the results as good news.

"The vast majority of people in the United States and the world probably have better access to primary care facilities rather than having access to academic centers, so to my patient population and to people I think in the vast majority, when we see that IV TPA is perhaps equivalent to more aggressive treatments that require more expansive techniques and depth of expertise, it’s kind of good news," she said to a round of applause.

Dr. Kidwell thanked her for the comment, but added, "I think there still are those among us who do believe that advanced neuroimaging, as well as endovascular therapy, will have a role down the line. I think we just need further trials with the new stent retriever devices to really sort this out."

MR RESCUE was funded by the National Institute of Neurological Disorders and Stroke. Concentric Medical Inc. provided study catheters and devices for part of the trial, with costs thereafter covered by study funds or third-party payers. Seven of the coauthors are employees of the University of California, which holds a patent on Merci Retriever devices. Dr. Chimowitz disclosed research support from the National Institutes of Health. Dr. Sacco reported no disclosures.