SPECIAL REVIEW Korean J Stroke 2011;13(3):99-106 http://dx.doi.org/10.5853/kjs.2011.13.3.99 2009 년한국뇌졸중진료지침에서뇌졸중이차예방중두개강외경동맥협착의수술또는중재적치료에관한내용의부분개정 서울대학교의과대학신경과학교실 1, 한림대학교의과대학신경과학교실 2, 서울대학교의과대학신경외과학교실 3, 인하대학교의과대학신경외과학교실 4, 인제대학교의과대학일산백병원신경과학교실 5, 연세대학교의과대학신경과학교실 6, 울산대학교의과대학신경과학교실 7, 가톨릭대학교의과대학신경외과학교실 8, 경상대학교의과대학신경외과학교실 9 정근화 1 유경호 2 권오기 3 박현선 4 홍근식 5 허지회 6 권순억 7 오창완 3 배희준 1 이병철 2 김성림 8 박인성 9 윤병우 1 Focused Update of 2009 Korean Clinical Practice Guidelines for the Surgical or Interventional treatment of Extracranial Carotid Artery Stenosis in Secondary Prevention of Stroke Keun-Hwa Jung 1, Kyung-ho Yu 2, O-Ki Kwon 3, Hyeon Seon Park 4, Keun-Sik Hong 5, Ji Hoe Heo 6, Sun-Uck Kwon 7, Chang Wan Oh 3, Hee-Joon Bae 1, Byung-Chul Lee 2, Seong-Rim Kim 8, In Sung Park 9 and Byung-Woo Yoon 1 1 Department of Neurology, Seoul National University College of Medicine, Seoul, 2 Department of Neurology, Hallym University College of Medicine, Chuncheon, 3 Department of Neurosurgery, Seoul National University College of Medicine, Seoul, 4 Department of Neurology, Inha University College of Medicine, Incheon, 5 Department of Neurology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, 6 Department of Neurology, Yonsei University College of Medicine, Seoul, 7 Department of Neurology, University of Ulsan College of Medicine, Ulsan, 8 Department of Neurosurgery, Catholic University College of Medicine, Seoul, 9 Department of Neurosurgery, Gyeongsang National University College of Medicine, Jinju, Korea Since the publication of the first edition of Korean clinical practice guidelines of secondary stroke prevention, encouraging data from recent large clinical trials and meta-analysis have led us to consider many therapeutic options in the treatment of symptomatic extracranial carotid stenosis. Accordingly, the writing group of Clinical Research Center for Stroke decided to provide recent views on the therapeutic revascularization of extracranial carotid stenosis, and timely evidence-based recommendations. In this updated version, new evidences about carotid angioplasty/stenting, treatment timing, and perioperative preparation are given, and qualifying conditions for operator are elucidated. This refinement was based on current consensus between Korean Society of Intravascular Neurosurgery, Korean Society of Interventional Neuroradiology, and Korean Society of Cerebrovascular Surgery and approved by Korean Stroke Society, Korean Neurological Association, and Korean Society of Geriatric Neurology. These recommendations are subject to future correction based on new evidences from ongoing and future studies. (Korean J Stroke 2011;13:99-106) KEY WORDS: Practice guideline, Symptomatic extracranial carotid artery stenosis, Carotid endarterectomy, Carotid artery angioplasty/stent Received: October 5, 2010 / Revised: August 13, 2011 / Accepted: August 14, 2011 Address for correspondence: Kyung-ho Yu, MD, PhD Department of Neurology, Hallym University College of Medicine, 896 Pyeongchon-dong, Dongan-gu, Anyang 430-070, Korea Tel: +82-31-380-3743, Fax: +82-31-381-4659, E-mail: ykh1030@hallym.ac.kr This study was supported by a grant of the Korean Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065). Copyright c 2011 Korean Stroke society ISSN 1229-4101 99
Update of CPG for Carotid Artery Stenosis 두개강외경동맥협착의치료에대한한국의뇌졸중진료지침 뇌졸중임상연구센터 (Clinical Research Center for Stroke) 진료지침집필위원회에서는 2007년 6월 30일까지발표된근거사항을반영하여제1판한국뇌졸중임상진료지침을 2009년 5월에발간하였다. 이후이차예방중유증상두개강외경동맥협착치료부분은최근임상진료에영향을미칠수있는대규모무작위배정연구결과들이다수발표되었다. 유증상의심한경동맥협착환자에서경동맥내막절제술의효과는확실히입증되어있었으나, 최근경동맥내막절제술과경동맥스텐트설치술의단기간및중장기효과및안전성비교연구들과이를기반으로한메타분석및소집단분석연구들이발표되었다. 이에따라외국의임상진료지침이개정되었고국내에서도많은논란이되고있어서, 집필위원회에서는한국뇌졸중임상진료지침의개정이필요하다고결정하였다. 임상진료지침개정과정은 2007년 7월 1일부터 2011년 2월 28일까지의유증상경동맥협착치료와관련된연구를문헌검색도구 (MEDLINE/PubMed, EMBASE, Best Evidence, Cochrane Library 검색도구 ) 를통하여추출하였고, 새로운임상시험과메타분석, 진료지침개정등의자료분석및비판을통하여대한민국의료현실에적합한개정안초안을마련하였다. 이후대한뇌졸중학회, 대한뇌혈관내수술학회, 대한신경중재치료학회, 대한뇌혈관외과학회로부터의자문및전문가회의를통한합의과정을통해서최종개정안을제안하게되었다. 본문에서는개정의근거가되는최근임상연구결과의제시와함께제1판한국뇌졸중임상진료지침에서이차예방중 < 대혈관협착-폐쇄질환에서수술또는중재적치료 > 부분에서두개강외경동맥협착에관한항목 (Table 1) 개정내용을기술하고자한다. 특히, 이번개정에서는경동맥협착환자의치료법을결정할때경동맥내막절제술, 경동맥스텐트설치술, 및약물치료를동시에고려할수있도록통합적인지침을제안하고자하였다. 유증상경동맥협착질환의임상연구 내막절제술의치료효과입증대규모연구일과성허혈발작이나뇌경색이최근 6개월이내에발생하였던심한내경동맥협착 (70-99%) 환자에서경동맥내막절제술은 30일째및 5년후뇌졸중발생및사망률을각각 6.2%, 15% 감소시키는효과가입증되어있다. 1 중등도협착 (50-69%) 에서는 5년후 6.5% 절대위험도감소효과를보였으나, 50% 미만의협착에서는약물치료군과비교할때유의한차이는없었다. 1 최근환자에게쉽게적용할수있는편의성때문에경동맥성형술및스텐트설치술이경동맥내막절제술의효과를대체할수있는지에대한관심이급증하고있다. 그러나, 유럽에서시행된 Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy (SPACE) 2,3 와 Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis trial (EVA-3S) 4,5 연구에서스텐트설치술군이내막절제술군에비하여수술후뇌졸중및사망위험도가높아연구가조기에종료된바있다. 비열등성임상연구 (noninferiority) 였던 SPACE 연구의 2년추적결과, 뇌졸중발생및사망률에서스텐트설치술과내막절제술간유의한차이가없었고 (9.5% vs. 8.8%, P=0.62)3, EVA-3S 연구의 4년추적결과에서도스텐트설치술군이내막절제술군에비해서더높은뇌졸중발생및사망률 (11.7% vs. 6.2%, P=0.03) 을보였다. 5 International Carotid Stenting Study (ICSS) 에서는색전보호기구를이용하여 TABLE 1. Korean guideline of surgical or interventional treatment of extracranial artery stenosis (May 2009) 3.4.1.1. 경동맥내막절제술 1. 최근 6개월이내에일과성허혈발작이나뇌경색이있었던심한내경동맥협착 ( 협착정도 70-99%) 환자는경동맥내막절제술을하는것이권장된다. 경동맥내막절제술수술은수술전후의이환율과사망률이낮은경험많은외과의사가시행하는것이권장된다. ( 근거수준Ib, 권고수준A) 2. 최근에일과성허혈발작이나뇌경색이있었던중등도내경동맥협착 (50-69%) 환자의경우환자의연령, 성별, 동반된질환, 처음증상의정도를고려하여경동맥내막절제술을시행할수있다. ( 근거수준Ib, 권고수준A) 3. 경도의내경동맥협착 (50% 미만 ) 환자에게는내과적인치료가우선권장된다. ( 근거수준Ib, 권고수준A) 4. 증상이없는중등도내경동맥협착 (60-99%) 을가진 40세-75세환자의경우, 기대수명이 5년이상이면경동맥내막절제술을고려하는것이바람직하다. ( 근거수준Ib, 권고수준A) 이경우수술전후의이환율과사망률이낮은경험많은외과의사가시행하는것이추천된다. 5. 경동맥내막절제술은허혈증상이발생한뒤 2주이내에시술하는경우더좋은예후를기대할수있다. ( 근거수준Ib, 권고수준A) 3.4.1.2. 경동맥성형술 / 스텐트 1. 의학적사유로경동맥내막절제술시행이어려운경우, 스텐트설치술이추천될수있다. ( 근거수준IIb, 권고수준B) 2. 시술전후의이환율과사망률이낮은숙련된중재시술자에게스텐트설치술을받는것이바람직하다. ( 근거수준IIb, 권고수준B) 3. 유증상의심한내경동맥협착 (70% 이상 ) 환자와무증상협착 (80% 이상 ) 환자에서스텐트설치술을고려할수있다. ( 근거수준IV, 권고수준C) 4. 스텐트설치술직전과시술후최소 1개월동안클로피도그렐과아스피린병용요법을유지하는것이고려된다. ( 근거수준IV, 권고수준C) 100 Korean J Stroke 2011;13:99-106
Keun-Hwa Jung, et al. ( 참여환자의 72% 에서사용 ) 스텐트설치술의안전성을높이는방법으로진행되었으나, 중간분석결과뇌졸중, 심근경색, 사망률이스텐트설치술군에서내막절제술군보다의미있게증가하는소견 (30일: 7.4% 대 4.0%, P=0.003; 3개월 : 8.5% vs. 5.2%, P=0.006) 을보였다. 6 스텐트의설치술후뇌졸중발생및사망률의증가는 SPACE, EVA-3S, ICSS를대상으로한메타분석에서도공통적으로증명되었고 (8.9% vs. 5.8%, P=0.0006), 7 자기공명영상을이용한 ICSS의소그룹분석에서 8 내막절제술에비하여스텐트설치술후 1일째확산강조자기공명영상에서새로운병변들이유의하게증가하였다 (50% vs. 17%; P<0.0001). 또한, 색전보호기구의사용이스텐트설치술과연관된색전증을감소시키지못했다. 경동맥성형술및스텐트설치술의대체가능성연구최근까지대규모연구들은유증상경동맥협착의치료법으로내막절제술이혈관성형술및스텐트설치술보다우월함을입증하였고, 미국및유럽의국가에서임상진료지침에이러한결과를반영하였다. 그러나, 경동맥스텐트설치술은여전히내막절제술을대체할수있는치료법으로제안되고있다. Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS) 9 과 Stenting and Angioplasty with Protection in Patients at High Risk of Endarterectomy (SAPPHIRE) 10 연구는고위험환자에서경동맥스텐트설치술이내막절제술의대체치료법으로사용될수있는가능성을제시하였다. SAPPHIRE 연구의 3 년추적결과와 11 CAVATAS 의 8년간장기추적결과에서 12 경동맥성형술및스텐트설치술이내막절제술과동등한정도의뇌졸중발생의감소효과를보였다. 무작위배정연구는아니었지만 Carotid revascularization using endarterectomy or stenting systems (CaRESS) 연구에 서도 13 유증상및무증상경동맥협착환자들을 4 년간추 적관찰하였을때재협착률은스텐트군에서높았지만뇌졸중, 사망, 심근경색발생은두군에서차이가없었다 ( 내막절제술 : 27.0%, 스텐트 : 21.7%, P=0.361). 특히, 80세미만의나이에서는스텐트설치술에의한뇌졸중위험도의감소가의미있게관찰되었다 (P=0.030). Carotid Revascularisation Endarterectomy Versus Stenting Trial (CREST) 은 14 유증상 (50% 이상협착 ) 과무증상 (60% 이상협착 ) 환자를모두포함하였고, 대상환자의 96% 에서색전보호기구를사용한가장최근의연구이다. 일차임상종료점은 4년동안의뇌졸중, 심근경색, 사망률로평가하였는데, 스텐트설치술과내막절제 술간에유의한차이가없었고 (7.2% vs. 6.8%; P=0.51), 증상유무나성별에따른아형분석에서도동일한소견을보였다. 시술또는수술이후 30일째까지의예후에서는스텐트설치술군이상대적으로뇌졸중의발생이많은반면 (4.1% vs. 2.3%, P=0.01), 내막절제술군에서는심근경색증발생이유의하게높았으며 (2.3% vs. 1.1%; P=0.03) 뇌신경장애의발생이많았다 (4.8% vs. 0.3%; P<0.0001). 이연구에서는스텐트설치술과내막절제술군간에일차임상종료점질환의발병양상에차이가있으므로치료효과해석에주의가필요하다. 최근까지대규모연구의해석과논란의쟁점현재까지의근거를바탕으로경동맥내막절제술이유증상경동맥협착의최우선치료법이라는점에는이견이없다. 그러나, 각연구의장단점과아형집단간분석연구를면밀히검토하여임상진료에반영해야할필요가있다. 우선연구마다일차임상종료점이다르다는점에유의해야한다. 공통적으로내막절제술의효과및안전성을제시했던 SPACE, EVA-3S, 및 ICSS 연구에서는 2,4,6 30일째뇌졸중발생및사망률을일차임상종료점으로정하였고이차임상종료점은중장기뇌졸중발생및사망률을분석하였다. 반면스텐트설치술과내막절제술간에동등한효과를보였던 CREST 연구는 14 일차임상종료점을 4년이내의뇌졸중, 심근경색증, 사망으로정함으로써중장기적안전성을고려하였다. 심근경색증의경우뇌혈관질환이있는환자에서흔히동반될수있고, 각종시술에따른합병증으로나타나기도한다. 따라서, ICSS나 CREST 연구와같이일차임상종료점에심근경색증을포함시켜분석을하는것은안전성평가에서중요한이슈가된다. 그러나, CREST 연구에서는심근경색발생과관련해서내막절제술의안전성문제를제기한반면, ICSS 연구에서는두그룹간차이를보이지않았다. 이러한상이한소견은심근경색정의의차이에기인할수있다. ICSS 연구가유증상심근경색만을포함한반면, CREST 연구에서는무증상심근손상도향후사망률을증가시킬수있다는가정하에심근효소를측정하여무증상심근손상까지심근경색범주에포함하였다. 무증상뇌경색병변을뇌졸중발생에포함할지여부, 심근경색과뇌경색사이의질병부담정도의차이해석이아직까지논란이되고있어, 두연구간분석방법및결과의차이는향후연구에서보완될것으로기대한다. 스텐트설치술의가장큰안정성저해요인은시술직후뇌졸중의발생률이높다는점이다. 색전보호기구 www.stroke.or.kr 101
Update of CPG for Carotid Artery Stenosis 사용도뇌졸중의발생을감소시키지못하였다. 반면, 내막절제술은수술직후심근경색과뇌신경장애의발생률이높다는점이위험요인으로지적된다. 그러나, 양측의약점모두, 치료직전충분한위험성평가와효과적인약물요법으로극복될수있는부분이다. 스텐트설치술의경우시술자, 기구, 술기경험을고려할때수술직후뇌졸중발생은지속적으로감소하는경향을보였고, 내막절제술의경우도국소마취를이용하여전신마취에따른부작용을줄여나가고있다. 따라서두가지시술은상호배타적이아닌, 보완적인치료법으로고려되어야한다. 치료시기에관한연구현재한국뇌졸중임상진료지침에서는 ECST 연구와 NASCET 연구의통합연구 15 결과를기반으로, 경동맥내막절제술을허혈증상이발생후 2주이내에시술하는것을권고하고있다. 그러나, 2주이내조기내막절제술에따른위험-이익평가가명확하게연구된바없다. 특히, 뇌졸중은초기에다양한임상경과를보이므로진행성뇌졸중이나일과성허혈발작, 뇌졸중의중증도에따라수술에따른위험부담이다르다. 최근 2008년까지발표된경동맥내막절제술연구자료를기반으로뇌졸중양상에따른수술시기별뇌졸중발생및사망위험도를분석한연구결과가발표되었다. 16 진행성뇌졸중의경우응급으로시행한내막절제술후뇌졸중발생및사망의절대위험도는 20.2% (95% 신뢰구간 : 12.0-28.4) 였고, 반복적, 진행성일과성허혈발작의경우절대위험도는 11.4% (95% 신뢰구간 :6.1-16.7) 였다. 그러나, 안정적인뇌졸중이나일과성허혈발작의경우에는응급및지연수술에따른수술위험도차이는없었다 (P=0.13). 뇌졸중양상에따른수술위험도의체계적연구는미흡하지만, 신경학적으로불안정한환자는수술위험도가높고, 뇌졸중발생및사망률이증가하는경향을보였다. 그러나, 수술시기에따른위험부담은환자의임상적특성을종합적으로평가하여판단해야한다. 환자나이에따른치료효과연구 CREST 연구에서는나이와치료효과사이의유의한연관성 (P=0.02) 이관찰되었는데 70세를기준으로 70세미만에서는스텐트설치술의효과가우수하였고 70세이상고령환자는내막절제술이우수한것으로관찰되었다. 14 SPACE, EVA-3S 및 ICSS 연구를메타분석한자료에서도 120일째뇌졸중발생및사망이 70세이상에서 는스텐트설치술군이내막절제술군에비해서유의하게높았고 (12.0% vs. 5.9%), 70세이하에서는두군간의차이가없었다 (5.8% vs. 5.7%, interaction P=0.0053). 7 반면, CaRESS 연구에서는 80세미만의환자에서는 4 년간뇌졸중및사망률이내막절제술군에서더높았고 (P=0.049), 80세이상의환자에서는유의한차이가없었다. 13 지금까지의연구결과는고령에서는스텐트설치술보다내막절제술이안전하고효과적인것으로제시하고있으나, 나이기준을진료지침에반영하기에는아직근거가부족한실정이다. 두개강외경동맥협착의치료법에대한외국의진료지침수정현황 2010년 10월 American Heart Association/American Stroke Association 에서뇌졸중또는일과성허혈발작환자들을위한뇌졸중예방치료진료지침개정판을발표하였다. 17 최근연구결과를바탕으로이번개정판에는두가지항목이포함되었다. 첫째는 50% 이상의유증상경동맥협착환자에서혈관내시술과관련된위험도가평균이하의환자에서는경동맥스텐트가내막절제술의대체치료로서사용될수있다는내용이다 (Class I, Level of Evidence B). 스텐트설치술관련합병증위험도는시술의사들의체계적인교육과첨단기구및기술의개발로향후에도지속적으로개선가능한항목으로써 CAVATAS, SAPPHIRE, CREST 의연구결과를반영한내용이다. 둘째로경동맥협착치료시항혈소판제, 지질저하제, 다른위험인자의조절필요성에대한항목이추가로언급되었다 (Class I, Level of Evidence B). 2011년 3월 American College of Cardiology Foundation (ACCF) 와 American Heart Association (AHA) 을주축으로내과학, 외과학, 신경학, 심장학, 영상의학, 혈관수술학, 신경외과학, 신경영상학, 중재영상학, 응급의학의전문가들이학술적합의과정을통해서두개강외경동맥협착환자들의치료를위한진료지침개정판을발표하였다 (Table 2). 18 이개정판에서도역시 50% 이상의유증상경동맥협착환자에서혈관내시술과관련된위험도가 6% 이하의환자에서는경동맥스텐트설치술이내막절제술의대체치료로서사용될수있다는내용이포함되었다 (Class I, Level of Evidence B). 또한, 경동맥협착치료시항혈소판제, 스타틴지질저하제, 위험인자의조절에대한항목이구체적으로기술되었는데, 특히, 두개강외경동맥협착증환자에서 LDL- 콜레스테롤을 100 mg/dl 이하로유지하기위해서 statin 계지질저하제를투여해야한다는내용이 Class I, Level of Evidence B로추가되었다. 치료 102 Korean J Stroke 2011;13:99-106
Keun-Hwa Jung, et al. TABLE 2. American and European Recommendations for Selection and Management of Patients for Carotid Revascularization American Recommendations (ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS, 2011) Patients at average or low surgical risk who experience nondisabling ischemic stroke or transient cerebral ischemic symptoms, including hemispheric events or amaurosis fugax, within 6 months (symptomatic patients) should undergo CEA if the diameter of the lumen of the ipsilateral internal carotid artery is reduced more than 70% as documented by noninvasive imaging (Class I; Level of Evidence: A) or more than 50% as documented by catheter angiography (Class I; Level of Evidence: B) and the anticipated rate of perioperative stroke or mortality is less than 6%. CAS is indicated as an alternative to CEA for symptomatic patients at average or low risk of complications associated with endovascular intervention when the diameter of the lumen of the internal carotid artery is reduced by more than 70% as documented by noninvasive imaging or more than 50% as documented by catheter angiography and the anticipated rate of periprocedural stroke or mortality is less than 6%. (Class I; Level of Evidence: B) Selection of asymptomatic patients for carotid revascularization should be guided by an assessment of comorbid conditions, life expectancy, and other individual factors and should include a thorough discussion of the risks and benefits of the procedure with an understanding of patient preferences. (Class I; Level of Evidence: C) It is reasonable to perform CEA in asymptomatic patients who have more than 70% stenosis of the internal carotid artery if the risk of perioperative stroke, MI, and death is low. (Class IIa; Level of Evidence: A) It is reasonable to choose CEA over CAS when revascularization is indicated in older patients, particularly when arterial pathoanatomy is unfavorable for endovascular intervention. (Class IIa; Level of Evidence: B) It is reasonable to choose CAS over CEA when revascularization is indicated in patients with neck anatomy unfavorable for arterial surgery. (Class IIa; Level of Evidence: B) When revascularization is indicated for patients with TIA or stroke and there are no contraindications to early revascularization, intervention within 2 weeks of the index event is reasonable rather than delaying surgery. (Class IIa; Level of Evidence: B) Prophylactic CAS might be considered in highly selected patients with asymptomatic carotid stenosis (minimum 60% by angiography, 70% by validated Doppler ultrasound), but its effectiveness compared with medical therapy alone in this situation is not well established. (Class IIb; Level of Evidence: B) In symptomatic or asymptomatic patients at high risk of complications for carotid revascularization by either CEA or CAS because of comorbidities, the effectiveness of revascularization versus medical therapy alone is not well established. (Class IIb; Level of Evidence: B) Aspirin (81 to 325 mg daily) is recommended before CEA and may be continued indefi nitely postoperatively. (Class I; Level of Evidence: A) Beyond the fi rst month after CEA, aspirin (75 to 325 mg daily), clopidogrel (75 mg daily), or the combination of low-dose aspirin plus extended-release dipyridamole (25 and 200 mg twice daily, respectively) should be administered for long-term prophylaxis against ischemic cardiovascular events. (Class I; Level of Evidence: B) Administration of antihypertensive medication is recommended as needed to control blood pressure before and after CEA. (Class I; Level of Evidence: C) The fi ndings on clinical neurological examination should be documented within 24 hours before and after CEA. (Class I; Level of Evidence: C) Patch angioplasty can be benefi cial for closure of the arteriotomy after CEA. (Class IIa; Level of Evidence: B) Administration of statin lipid-lowering medication for prevention of ischemic events is reasonable for patients who have undergone CEA irrespective of serum lipid levels, although the optimum agent and dose and the effi cacy for prevention of restenosis have not been established. (Class IIa; Level of Evidence: B) Noninvasive imaging of the extracranial carotid arteries is reasonable 1 month, 6 months, and annually after CEA to assess patency and exclude the development of new or contralateral lesions. Once stability has been established over an extended period, surveillance at longer intervals may be appropriate. Termination of surveillance is reasonable when the patient is no longer a candidate for intervention. (Class IIa; Level of Evidence: C) Before and for a minimum of 30 days after CAS, dual-antiplatelet therapy with aspirin (81 to 325 mg daily) plus clopidogrel (75 mg daily) is recommended. For patients intolerant of clopidogrel, ticlopidine (250 mg twice daily) may be substituted. (Class I; Level of Evidence: C) Administration of antihypertensive medication is recommended to control blood pressure before and after CAS. (Class I; Level of Evidence: C) The fi ndings on clinical neurological examination should be documented within 24 hours before and after CAS. (Class I; Level of Evidence: C) Embolic protection device (EPD) deployment during CAS can be beneficial to reduce the risk of stroke when the risk of vascular injury is low. (Class IIa; Level of Evidence: C) Noninvasive imaging of the extracranial carotid arteries is reasonable 1 month, 6 months, and annually after revascularization to assess patency and exclude the development of new or contralateral lesions. Once stability has been established over an extended period, surveillance at extended intervals may be appropriate. Termination of surveillance is reasonable when the patient is no longer a candidate for intervention. (Class IIa; Level of Evidence: C) www.stroke.or.kr 103
Update of CPG for Carotid Artery Stenosis TABLE 2. Continued European Stroke Organization (ESO) guideline (European Stroke Organization, 2008) CEA is recommended for patients with 70-99% stenosis (Class I, Level A). CEA should only be performed in centres with a perioperative complication rate (all strokes and death) of less than 6% (Class I, Level A) It is recommended that CEA be performed as soon as possible after the last ischaemic event, ideally within 2 weeks (Class II, Level B) It is recommended that CEA may be indicated for certain patients with stenosis of 50-69%; males with very recent hemispheric symptoms are most likely to benefi t (Class III, Level C). CEA for stenosis of 50-69% should only be performed in centres with a perioperative complication rate (all stroke and death) of less than 3% (Class I, Level A) CEA is not recommended for patients with stenosis of less than 50% (Class I, Level A) It is recommended that patients remain on antiplatelet therapy both before and after surgery (Class I, Level A) Carotid percutaneous transluminal angioplasty and/or stenting (CAS) is only recommended in selected patients (Class I, Level A). It should be restricted to the following subgroups of patients with severe symptomatic carotid artery stenosis: those with contra-indications to CEA, stenosis at a surgically inaccessible site, re-stenosis after earlier CEA, and post-radiation stenosis (Class IV, GCP). Patients should receive a combination of clopidogrel and aspirin immediately before and for at least 1 month after stenting (Class IV, GCP) ASA: American Stroke Association, ACCF: American Association College of Cardiology Foundation, AHA: American Heart Association, AANN: American Association of Neuroscience Nurses, AANS: American Association of Neurological Surgeons, ACR: American College of Radiology, ASNR: American Society of Neuroradiology, CNS: Congress of Neurological Surgeons, SAIP: Society of Atherosclerosis Imaging and Prevention, SCAI: Society for Cardiovascular Angiography and Interventions, SIR: Society of Interventional Radiology, SNIS: Society of NeuroInterventional Surgery, SVM: Society for Vascular Medicine, SVS: Society for Vascular Surgery. 전후항혈전제사용, 특히스텐트설치술이후최소 30일동안은아스피린과클로피도그렐을병합투여해야한다는것이 Class I, Level of Evidence B로추가되었다. 반면, 2008년개정된 European Union Stroke Initiative (EUSI) 에서는 19 경동맥성형술및스텐트설치술의사용을고위험환자 ( 내막절제술의금기증, 수술이불가능한병변, 수술후재협착, 방사선치료후협착 ) 로제한하고있다 (Table 2). 그러나스텐트설치술후항혈소판제병합투여를최소 1달간유지하도록하는권고안은미국의진료지침과일치하였다. 치료시점에대한내용은미국, 유럽모두 2주이내에시행을추천하고있지만, 미국진료지침에는조기수술의금기사항이없어야한다는단서가포함되었다 (Class IIa, Level of Evidence B). 이는불안정한뇌졸중환자에서응급수술과관련된위험도가증가한다는통합분석결과가반영된것으로보인다. 한국뇌졸중임상진료지침개정사항 제1판에서는유증상두개강외경동맥협착치료부분에서무증상경동맥협착치료까지언급하여기술한바있다. 이번개정에서는혼동을초래할수있는무증상경동맥협착부분은일차예방에서기술하기로하고삭제하였다. 이를위해서유증상경동맥협착이무증상경동맥협착과확실히구별될수있도록정의부분을지침에추가하였는데, 유증상경동맥협착은최근 6개월이내에협착영역에일과성허혈발작이나뇌경색이있었던경우로정의하였다. 최근에발표된 SPACE, EVA-3S, ICSS 등대부분의연 구는경동맥협착증치료법으로경동맥내막절제술을지지하였다. 그러나, CAVATAS, SAPPHIRE 등장기간추적관찰연구에서는선별된환자의경우혈관성형술및스텐트설치술이내막절제술의대체치료법으로사용될수있는근거를보여주었다. CREST 연구에서도스텐트설치술이경동맥내막절제술과비교해서심근경색발생관련안전성과 70세미만환자에서치료효과가우월함이제시되었다. 2009년제1판뇌졸중임상진료지침에서는경동맥내막절제술과경동맥성형술및스텐트설치술에대한근거자료와권고사항을나누어기술하였다 (Table 1). 그러나, 스텐트설치술과내막절제술이서로다른적응증을가지기보다는상호보완적으로사용될수있기때문에이번개정판에서는기존의분리된진료지침을하나로통합하여기술하였다 (Table 3). 이번개정에서가장특징적인것중하나는유증상내경동맥협착 (50% 이상 ) 을가진환자에서스텐트설치술이내막절제술의대체치료로사용될수있다는문구를근거수준 Ib, 권고수준 A로제시하였다는것이다. 그러나, 스텐트설치술의효과는환자의나이, 약물, 기구, 시술자의경험에따라차이가날수있다. 따라서, 이번개정판에는최근 CREST 결과가반영된미국뇌졸중학회진료지침을참고하여 유증상내경동맥협착 (50% 이상 ) 을가진환자에서스텐트설치술이내막절제술의대체치료로사용될수있다. 라는문구에 단, 내막절제술또는스텐트설치술을선택할때, 환자의나이, 센터의특성, 수술전후의뇌졸중발생률및사망률을고려할필요가있다 는문구를삽입하였다 (Good practice point, GPP). 104 Korean J Stroke 2011;13:99-106
Keun-Hwa Jung, et al. TABLE 3. Updated recommendation for treatment of symptomatic extracranial carotid artery stenosis (Korean Clinical Practice guidelines for stroke from Clinical Research Center for Stroke, December 2011) 1. 유증상의 ( 최근 6개월이내에협착영역에일과성허혈발작이나뇌경색이있었던경동맥협착 ) 심한내경동맥협착 ( 협착정도 70-99%) 환자는경동맥내막절제술을시행하는것이권장되며, 경동맥내막절제술은수술전후의뇌졸중발생률또는사망률이 6% 미만인의사가시행하는것이권장된다 ( 근거수준Ib, 권고수준A). 2. 유증상의중등도내경동맥협착 ( 협착정도 50-69%) 환자의경우환자의연령, 성별, 동반된질환, 처음증상의정도를고려하여경동맥내막절제술을시행할수있다 ( 근거수준Ib, 권고수준A). 3. 유증상의경도의내경동맥협착 (50% 미만 ) 환자에게는내과적인치료가우선권장된다 ( 근거수준Ib, 권고수준A). 4. 경동맥내막절제술은조기수술의금기사항이없다면허혈증상이발생한뒤 2주이내에시술하는경우더좋은예후를기대할수있다 ( 근거수준 IIb, 권고수준B) 스텐트설치술의수술시기에대한근거자료는아직없다. 5. 유증상내경동맥협착 (50% 이상 ) 을가진환자에서 6% 미만의뇌졸중발생률또는사망률이이예측되는경우스텐트설치술이내막절제술의대체치료로사용될수있다. ( 근거수준Ib, 권고수준A) 단, 내막절제술또는스텐트설치술을선택할때, 환자의나이, 성별, 병원의특성을고려할필요가있다 (GPP). 6. 스텐트설치술직전과시술후최소1개월동안클로피도그렐과아스피린병용투여를유지하는것이추천된다 ( 근거수준IIb, 권고수준B). 7. 유증상경동맥협착치료과정에서항혈소판제및스타틴계지질저하제사용, 위험인자의적극적인조절이병행되어야한다 ( 근거수준IIb, 권고수준B). GPP: good practice point. 내막절제술후이환율과사망률은대규모연구에서 3-6% 였으나스텐트설치술후뇌졸중발생및사망률은 6-10% 로이를상회하였다. 최근미국, 유럽의개정진료지침에서는 17-19 수술관련최대허용위험도를 6% 로제안하고있기때문에이번개정내용에는수술의사의자격을구체화하는것이필요할것으로판단되었다. 따라서, 경동맥내막절제술수술은수술전후의이환율과사망률이낮은경험많은외과의사가시행하는것이권장된다 는문구는 뇌졸중발생률또는사망률이 6% 미만인의사가시행하는것이권장된다 는문구로수정하였다. 수술시기는미국뇌졸중학회의개정지침에도기술된바와같이불안정한뇌졸중의경우조기수술에따른합병증발생의위험성이증가할수있으므로 조기수술의금기사항이없다면 이라는문구를추가하였고, 근거수준과권고수준을하향수정하였다. 스텐트설치술의효과는약물, 기구, 시술자의경험에따라차이가날수있다. 뇌졸중발생률또는사망률이 6% 미만으로감소될수있다면혈관성형술및스텐트설치술의중장기적인안전성, 유효성도증가할수있다. 따라서, 이번개정판에는최근 CREST 결과가반영된미국뇌졸중학회진료지침을참고하여 유증상내경동맥협착 (50% 이상 ) 을가진환자에서 6% 미만의뇌졸중발생률또는사망률이예측되는경우스텐트설치술이내막절제술의대체치료로사용될수있다. 라는문구를근거수준 Ib, 권고수준 A로제시하였다. 경동맥협착환자의치료효과를높이기위해서는적절한약물치료병행을통해서수술및시술직후뇌졸중및심근경색발생을줄이는것이중요하다. 유증상경동맥협착증의치료과정에서항혈소판제및스타틴계지질저하제사용, 위험인자의적극적인조절이병행되어야한다는문구를근거수준 IIb, 권고수준 B로포함하였다. 기존에언급된스텐트 설치술직전과시술후최소 1개월동안클로피도그렐과아스피린병용투여를유지하는것이고려된다는문구는근거수준 IIb, 권고수준 B로상향조정하였다. Conflicts of Interest The authors have no financial conflicts of interest. REFERENCES 1. Rothwell PM, Eliasziw M, Gutnikov SA, Fox AJ, Taylor DW, Mayberg MR, et al. Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet 2003;361:107-115. 2. The SPACE Collaborative Group. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet 2006;368:1239-1247. 3. Eckstein HH, Ringleb P, Allenberg JR, Berger J, Fraedrich G, Hacke W, et al. Results of the Stent- Protected Angioplasty versus Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomized trial. Lancet Neurol 2008;7:893-902. 4. Mas JL, Chatellier G, Beyssen B, EVA-3S Investigators. Carotid angioplasty and stenting with and without cerebral protection: clinical alert from the Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S) trial. Stroke 2004;35:e18-20. 5. Mas JL, Trinquart L, Leys D, Albucher JF, Rousseau H, Viguier A, et al. Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial: results up to 4 years from a randomised, multicentre trial. Lancet Neurol 2008; 7: 885-892. 6. Ederle J, Dobson J, Featherstone RL, Bonati LH, van der Worp HB, de Borst GJ, et al. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet 2010;375:985-997. 7. Carotid Stenting Trialists Collaboration. Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: a preplanned meta-analysis of individual patient data. Lancet 2010;376:1062-1073. 8. Bonati LH, Jongen LM, Haller S, Flach HZ, Dobson J, Nederkoorn PJ, et al, for the ICSS-MRI study group. New ischaemic brain lesions www.stroke.or.kr 105
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