종설 건국대학교의학전문대학원신경과학교실, 가톨릭대학교의과대학신경외과학교실 a, 성균관대학교의과대학영상의학교실 b, 서울대학교의과대학신경외과학교실 c, 을지대학교의과대학신경과학교실 d, 가톨릭대학교의과대학신경과학교실 e, 인제대학교의과대학일산백병원신경과학교실 f, 인제대학교의과대학상계백병원신경과학교실 g, 한림대학교의과대학신경과학교실 h, 인하대학교의과대학신경과학교실 i, 연세대학교의과대학신경과학교실 j, 울산대학교의과대학신경과학교실 k, 서울대학교의과대학신경과학교실 l 김한영김성림 a 전평 b 강현승 c 강규식 d 구자성 e 박종무 d 조용진 f 한상원 g 유경호 h 나정호 i 허지회 j 권순억 k 오창완 c 배희준 l 이병철 h 윤병우 l 홍근식 f Management of Asymptomatic Carotid Stenosis for Primary Stroke Prevention: 2012 Focused Update of Korean Clinical Practice Guidelines for Stroke Hahn Young Kim, MD, PhD, Seong-Rim Kim, MD, PhD a, Pyoung Jeon, MD, PhD b, Hyun-Seung Kang, MD, PhD c, Kyusik Kang, MD, PhD d, Jaseong Koo, MD, PhD e, Jong-Moo Park, MD, PhD d, Yong-Jin Cho, MD, PhD f, Sang Won Han, MD, PhD g, Kyung-Ho Yu, MD, PhD h, Joung-Ho Rha, MD, PhD i, Ji Hoe Heo, MD, PhD j, Sun-Uck Kwon, MD, PhD k, Chang Wan Oh, MD, PhD c, Hee-Joon Bae, MD, PhD l, Byung-Chul Lee, MD, PhD h, Byung-Woo Yoon, MD, PhD l, Keun-Sik Hong, MD, PhD f Department of Neurology, Konkuk University College of Medicine, Seoul, Korea Department of Neurosurgery a, Catholic University College of Medicine, Seoul, Korea Department of Radiology b, Sungkyunkwan University School of Medicine, Seoul, Korea Department of Neurosurgery c, Seoul National University College of Medicine, Seoul, Korea Department of Neurology d, Eulji University College of Medicine, Seoul, Korea Department of Neurology e, Catholic University College of Medicine, Seoul, Korea Department of Neurology f, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea Department of Neurology g, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea Department of Neurology h, Hallym University College of Medicine, Seoul, Korea Department of Neurology i, Inha University College of Medicine, Incheon, Korea Department of Neurology j, Yonsei University College of Medicine, Seoul, Korea Department of Neurology k, University of Ulsan College of Medicine, Seoul, Korea Department of Neurology l, Seoul National University College of Medicine, Seoul, Korea Received July 6, 2011 Revised October 19, 2011 Accepted October 19, 2011 *Keun-Sik Hong, MD, PhD Department of Neurology, Ilsan Paik Hospital, Inje University College of Medicine, 170 Juhwa-ro, Ilsanseo-gu, Goyang 411-706, Korea Tel: +82-31-910-7680 Fax: +82-31-910-7368 E-mail: nrhks@paik.ac.kr *This work is supported by the grant of the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065). J Korean Neurol Assoc Volume 30 No. 2, 2012 77
김한영김성림전평강현승강규식구자성박종무조용진한상원유경호나정호허지회권순억오창완배희준이병철윤병우홍근식 Extracranial carotid stenosis is a well-established, modifiable risk factor for stroke. Asymptomatic extracranial carotid stenosis is increasingly being detected due to the introduction of less-invasive and more-sensitive advanced diagnostic technologies. For severe asymptomatic stenosis, earlier pivotal clinical trials demonstrated the benefit of carotid endarterectomy over the best medical therapy. Since then, great advances have been made in interventional and medical therapies as well as surgical techniques. The first edition of the Korean Stroke Clinical Practice Guidelines for primary stroke prevention for the management of asymptomatic carotid stenosis reflected evidences published before June 2007. After the publication of the first edition, several major clinical trials and observational studies have been published, and major guidelines updated their recommendation. Accordingly, the writing group of Korean Stroke Clinical Practice Guidelines (CPG) decided to provide timely updated evidence-based recommendations. The Korean Stroke CPG writing committee has searched and reviewed literatures related to the management of asymptomatic carotid stenosis including published guidelines, meta-analyses, randomized clinical trials, and nonrandomized studies published between June 2007 and Feb 2011. We summarized the new evidences and revised our recommendations. Key changes in the updated guidelines are the benefit of intensive medical therapy and further evidence of carotid artery stenting as an alternative to carotid endarterectomy. The current updated guidelines underwent extensive peer review by experts from the Korean Stroke Society, Korean Society of Intravascular Neurosurgery, Korean Society of Interventional Neuroradiology, Korean Society of Cerebrovascular Surgery, and Korean Neurological Association. New evidences will be continuously reflected in future updated guidelines. J Korean Neurol Assoc 30(2):77-87, 2012 Key Words: Asymptomatic carotid stenosis, Clinical practice guidelines, Primary prevention, Stroke 뇌졸중일차예방에있어서무증상경동맥협착에대한한국뇌졸중진료지침개정의필요성 허혈뇌졸중의 15~20% 는두개강외경동맥협착에의해발생한다. 진단기술의발전으로무증상경동맥협착의발견이증가하고있는데, 65세이상에서 50% 이상의협착은 5~10%, 80% 이상의협착은약 1% 정도로보고하고있다. 1,2 50~99% 의무증상경동맥협착을가지고있는경우매년뇌졸중발생률은약 1~3.4% 로알려졌다. 3 무증상경동맥협착의치료는내과적치료와경동맥내막절제술 (carotid endarterectomy) 을비교한임상시험결과가 1990 년대와 2000 년대초반에발표된이후, 내과적치료와경동맥혈관성형 / 스텐트설치술 (carotid angioplasty and stenting) 의발전이있었으며, 수술방법도발전하였다. 따라서환자와임상의사는선택의폭이넓어졌지만, 한편으로는어떤치료법이최선의선택인지를고민해야한다. 한국뇌졸중진료지침은 2007 년 6월 30일까지발표된근거자료를검토하여 2009 년 10월단행본 1판이발간되었다. 4 이후임상진료에영향을줄수있는주요연구결과들이다수발표됨에따라뇌졸중진료지침집필위원회에서는이를반영할필요가있다고판단하였다. 이에따라뇌졸중일차예방집필위원회는문헌검색과전문가의의견을수렴하여개정이필요하다고판단한주제를선정하였는데, 뇌졸중일차예방중무증상경동맥협착에대한내용도개정하기로결정하였다. 뇌졸중일차예방에있어서무증상경동맥협착 (asymptomatic carotid stenosis for primary stroke prevention) 주제와관련하여 MEDLINE/PubMed, EMBASE, Best Evidence, Cochrane Library 같은문헌검색도구를이용하여 2007 년 7월 1일부터 2011 년 2월 28 일까지발표된메타분석, 체계적고찰 (systematic review), 무작위배정임상시험을검색하였는데, 2개의무작위배정임상시험과 5,6 1개의메타분석, 7 1개의인구집단기반연구 (population-based study) 8 가있었다. 또한이기간동안 European Stroke Organization (ESO, 2008 년 ) 9 과 American Heart Association/American Stroke Association (AHA/ ASA) 의뇌졸중일차예방진료지침 (2010 년 ) 3 과두개외경동맥과경추동맥질환의진료지침 (2011 년 ) 을 10 발표하였다. 본논문에서는 2007 년 7월 1일부터 2011 년 2월 28일사이에발표된개정의근거가되는연구결과와 ESO 와 AHA/ASA 에서제시한최신진료지침을정리하여기술하고, 이를바탕으로뇌졸중일차예방에있어서무증상경동맥협착에관한진료지침을근거수준 (Level of Evidence), 권고수준 (Grade of Recommendation) 과함께개정하여제시하고자한다. 본진료지침에서사용되는근거수준과권고수준결정방식은 2009 년제1판진료지침과동일하게근거수준에따라권고수준이정해지는 1993 년에발표된 US Agency for Health Care Policy and Research( 현재는 Agency for Healthcare Research and Quality [AHRQ]) 방식 11 을따르고있다 (Table 1). 진료지침이란일반적인상황에대하여과학적근거가있는진료행위를제시함으로써의사와환자의판단에도움을주기위한것이목적이므로, 개개환자에대한진료행위는담당의사 78 대한신경과학회지제 30 권제 2 호, 2012
가환자의여러상황을고려하여환자와상의후최종적으로결정하여야한다. 따라서본진료지침은현장에서진료를담당하는의료인의의료행위를제한하거나, 건강보험심사의기준으로이용되어서는안되며, 특히개개환자에게여러상황을고려하여시행된진료행위를일반적인상황에대한진료지침을기준으로삼아법률적판단을하여서는안됨을다시한번강조한다. 무증상경동맥협착의정의 무증상경동맥협착은경동맥협착영역에허혈뇌졸중증상을유발한병력이없는협착을의미한다. 그러나연구에따라정의가다른데, 무증상경동맥협착의대표적임상시험인 Veterans Affairs Cooperative Study (VACS), 12 Asymptomatic Carotid Atherosclerosis Study (ACAS), 13 Asymptomatic Carotid Surgery Trial (ACST) 14 연구에서 VACS 와 ACAS 는경동맥협착영역에허혈뇌졸중이없었던경우로정의하였지만, ACST 연구는무증상뿐아니라최근 6개월이내증상이없었던경우도포함하였다. 증상경동맥협착의대표적연구인 European Carotid Surgery Trial (ECST) 는 6개월이내증상이있었던경우 를 15 North American Symptomatic Carotid Endarterectomy Trial (NASCET) 연구는 4개월이내증상이있었던경우를증상경동맥협착으로정의하였다. 16 최근연구에서도차이가있어 Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) 연구에서는 120 일이내증상이있었던경우를증상성경동맥협착으로정의하였으나, 17 Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) 6 와 Stent-Supported Percu- Table 1. Level of Evidence and Grade of Recommendation in Korean Stroke Guidelines Level Type of Evidence Recommendation Ia Evidence obtained from meta-analysis of randomized controlled trials. A Ib Evidence obtained from at least one randomized controlled trial. A IIa Evidence obtained from at least one well-designed controlled study without randomization. B IIb Evidence obtained from at least one other type of well-designed quasi-experimental study. B III Evidence obtained from well-designed non-experimental descriptive studies, such as comparative B studies, correlation studies and case studies. IV Evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities. C, GPP (Good Practice Point) Table 2. 2009 Korean Clinical Practice Guidelines for the asymptomatic carotid stenosis in primary prevention of stroke 4 2009년제1판진료지침작성시참고한외국의권고사항 1. It is recommended that patients with asymptomatic carotid artery stenosis be screened for other treatable causes of stroke and that intensive therapy of all identified stroke risk factors be pursued (GPP). 2. The use of aspirin is recommended unless contraindicated because aspirin was used in all of the cited trials as an antiplatelet drug except in the surgical arm of 1 study, in which there was a higher rate of MI in those who were not given aspirin (ASA: LOE IIa, GOR B). 3. Prophylactic carotid endarterectomy is recommended in highly selected patients with 60% and <100% carotid stenosis, performed by surgeon with surgical morbidity/mortality rate <3%. Careful patient selection should be guided by comorbid conditions, life expectancy, patient preference, and other individual factors. Patients with asymptomatic stenosis should be fully evaluated for other treatable causes of stroke (ASA: LOE Ia, GOR A). 4. Carotid angioplasty stenting might be a reasonable alternative to endarterectomy in asymptomatic patients at high risk for the surgical procedure (ASA: LOE IIa, GOR B). 5. Carotid surgery may be indicated for some asymptomatic patients with a 60-99% stenosis of the ICA. The CEA-related risk for stroke or death must be less than 3%, and patients with a life expectancy of at least 5 years (or under the age of 80) may benefit from surgery (EUSI: LOE Ia, GOR A). 6. Carotid angioplasty, with or without stenting, is not routinely recommended for patients with asymptomatic carotid stenosis. It may be considered in the context of randomised clinical trials (EUSI: LOE IIa, GOR B). 국내의권고사항 1. 무증상경동맥협착환자에서뇌졸중의다른치료가능한위험인자가있는지를선별하고발견된위험인자에대하여집중적인치료를해야한다 (GPP). 2. 50% 이상의무증상경동맥협착환자에서금기사항이없는한항혈소판제제치료가권장된다 ( 근거수준 IIa, 권고수준 B). 50% 미만인경우, 환자의상황에따라항혈소판제제치료유무를결정하는것이바람직하다 (GPP). 3. 60-99% 무증상경동맥협착에서수술관련이환율및사망률이 3% 미만인경우예방적경동맥내막절제술이추천된다. 수술대상환자의선택에있어동반된질환, 기대여명, 환자의선호도와기타개인별요인들을신중하게고려하는것이필요하다 ( 근거수준 Ia, 권고수준 A). 4. 중증의무증상경동맥협착환자에서수술위험성을높이는동반질환이있는경우경동맥혈관성형술및스텐트설치술이경동맥내막절제술의대안으로추천될수있다 ( 근거수준 IIa, 권고수준 B). J Korean Neurol Assoc Volume 30 No. 2, 2012 79
김한영김성림전평강현승강규식구자성박종무조용진한상원유경호나정호허지회권순억오창완배희준이병철윤병우홍근식 taneous Angioplasty of the Carotid Artery versus Endarterectomy (SPACE) 18 연구에서는 180 일이내증상이있었던경우를증상성협착으로정의하였다. 따라서무증상경동맥협착을일률적으로정의할수는없지만 6개월이내협착영역에허혈뇌졸중증상이없었던경우를무증상경동맥협착으로고려하는것이가장타당하다고생각한다. 뇌졸중일차예방에있어서무증상경동맥협착 - 개정전권고사항 2009 년제1판진료지침을기술할당시, 주요외국진료지침의무증상경동맥협착에대한권고사항과개정전국내진료지침의권고사항은 Table 2와같다. 2009 년국내진료지침의권고사항은 2007 년 6월 30일까지발표된 5개의무작위배정임상시험과이를바탕으로한 1개의메타분석결과와 2004 년에발표된유럽의 European Union Stroke Initiative (EUSI) 진료지침과 2006 년에발표된미국의 AHA/ASA 진료지침을고려하여작성한것이다. 12-14,19-21 요약하면무증상경동맥협착환자에서다른치료가능한뇌졸중위험인자에대한검사와치료를집중적으로하는것과함께, 50% 이상협착의경우에는금기사항이없는한항혈소판제제치료를권장하였다. 21 60~99% 무증상경동맥협착의경우에는수술관련이환율과사망률이 3% 미만인경우신중하게선택된환자에서예방적경동맥내막절제술을추천하였는데, 이권고사항은 50~60% 이상의무증상경동맥협착을대상으로시행한 VACS, 12 ACAS, 13 ACST 14 연구결과와이연구의메타분석결과에 19 근거를둔것이었다. 경동맥혈관성형 / 스텐트설치술 (carotid angioplasty and stenting) 은 Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) 임상시험결과에근거하여경동맥내막절제술의위험도가높은심한무증상경동맥협착환자에서대안으로권고하였다. 20 2007 년 7 월 1 일부터 2011 년 2 월 28 일사이에발표된주요연구결과 인구집단코호트연구결과지난 50년간뇌졸중위험인자조절이향상되면서뇌졸중발생률과사망률이감소하고있고, 22 무증상경동맥협착에의한뇌졸중발생률또한내과적치료의발전으로감소하고있다. 8,23 무증상경동맥협착에대한내막절제술의유용성을보여준 2가지대규모연구인 VACS 12 와 ACAS 13 연구가진행된 1990년대당시최선의내과적치료는혈압조절, 당뇨조절, 아스피린사용에국한되어있었다. 이후발전된약물치료의근간이되는스타틴과차세대항혈소판제제의사용이아직정립되지않은시기의연구결과로당시최선의내과적치료가현재와는많이달랐다. 환자가연구에참여한시기별로무증상경동맥협착에의한뇌졸중발생률을비교한연구에따르면, VACS 와 ACAS 12 연구가진행되었던 13 1980~1990년대의경우연간뇌졸중발생률이 2~3% 였던것에비하여, 2000 년대이후의진행되었던연구에서는 1% 내외의연간뇌졸중발생률을보이고있다. 8 이러한추세는적극적인위험인자관리, 새로운항혈소판제의개발, 스타틴제제가발달함에따라최근 25년간내과적치료군에서뇌졸중발생률의감소를반영한다. 2000 년대이후연구에서는내과적치료만시행해도수술성적이우수하였던 1990 년대에발표된주요임상시험의수술군의뇌졸중발생률과비슷하거나오히려낮아지고있다. 따라서뇌졸중발생률이낮은무증상경동맥협착의경우에는수술적치료에비해상대적으로안전하고경제적인내과적치료의중요성을강조하면서, 내과적치료가무증상경동맥협착에대한가장적절한치료법이라는결과를발표하기도하였다. 7 이러한무증상경동맥협착환자에서뇌졸중발생률의감소와내과적치료의중요성에대한내용을소개하고, 무작위배정임상시험결과와메타분석결과를소개하고자한다. 1. Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: A prospective, population-based study 8 인구집단기반연구인 Oxford Vascular study 에서 2002 년부터 2009 년사이에일과성허혈발작또는뇌졸중이발생한환자 1153 명중에서 50% 이상의무증상경동맥협착이발견된 101 명환자를대상으로시행된연구로 2010 년에발표되었다. 이환자에게집중적내과적치료 (intensive medical therapy) 를시행하면서무증상경동맥협착에의한일과성허혈발작또는뇌졸중발생여부를 301 환자 -년( 평균 3년 ) 동안추적관찰하였다. 무증상경동맥협착이있던혈관영역에서 6건의뇌허혈증상 (1건의경미한허혈뇌졸중과 5건의일과성허혈발작 ) 이발생하였다. 뇌허혈증상의평균연간발생률은동측허혈뇌졸중 0.34% (95% CI, 0.01 to 1.87), 장애를남기는동측뇌졸중 0% (95% CI, 0.00 to 0.99), 동측일과성허혈발작 1.78% (95% CI, 0.58 to 4.16) 였다. 결론적으로최근 10년간무증상경동맥협착이동반된뇌졸중환자에게집중적내과적치료를시행한결과, 무증상경동맥협착에의한뇌졸중발생률은매우낮았다. 하지만아직집중적또는최선의내과적치료에대한정의가 80 대한신경과학회지제 30 권제 2 호, 2012
정립되어있지않으며, 국내에서시행된연구가아니라는점에서한국뇌졸중진료지침으로일반화하여적용하는데신중한고려가필요하다. 그러나무증상경동맥협착에의한동측허혈증상발생율이 2000 년대이전에비해서최근 10년간감소하고있음을보여주는연구결과이다. 또한이연구의대상이일과성허혈발작또는뇌졸중이있었던뇌졸중고위험군인것을고려하면일과성허혈발작이나뇌졸중의병력이없는환자에서발견된무증상경동맥협착의뇌졸중발생위험은더낮을수도있다. 2. Medical (nonsurgical) intervention alone is now best for prevention of stroke associated with asymptomatic severe carotid stenosis: results of a systematic review and analysis 7 지난 25년간심한무증상경동맥협착환자의내과적치료군에서뇌졸중발생위험을체계적으로검토 (systematic review) 한연구로 2009 년에발표되었다. 최근의내과적치료효과가반영된 2000 년대이후에수행된연구에서는동측과전체일과성허혈발작또는뇌졸중발생률이 1980 년대중반에비해서현저히감소하고있으므로, 내과적치료가경동맥내막절제술에비해서비용대비효과 (cost-effectiveness) 가 3~8 배우수할것으로추정하였다. 저자는내과적치료가무증상경동맥협착환자에서흔히동반되는다른심혈관질환에대해서도예방효과가있다는점과아직까지는예방적경동맥내막절제술또는경동맥혈관성형 / 스텐트설치술이필요한고위험무증상경동맥협착환자군을선별하기어렵다는점을감안하여내과적치료가더우월하다고주장하였다. 그러나약제비, 경동맥내막절제술, 경동맥혈관성형 / 스텐트설치술의비용, 그리고이러한시술이가능한 3차의료기관의접근성에있어이연구와우리나라의상황이다르므로국내실정을고려한비용대비효과분석이필요하다. 3. Stenting versus endarterectomy for treatment of carotid-artery stenosis 6 증상경동맥협착과무증상경동맥협착환자를대상으로한무작위배정임상시험인 CREST 연구결과가 2010 년에발표되었다. 일차결과변수 (primary endpoint) 는수술또는혈관성형 / 스텐트설치술 30일이내뇌졸중, 심근경색, 사망과 4년이내동측뇌졸중발생률이었다. 증상경동맥협착의기준은고식적혈관조영술에서 50% 이상, 초음파 70% 이상, CT 혈관촬영술또는 MR 혈관촬영술 70% 이상 ( 초음파에서 50~69% 협착인경우 ) 이 었고, 무증상경동맥협착의기준은고식적혈관조영술에서 60% 이상, 초음파 70% 이상, CT 혈관촬영술또는 MR 혈관촬영술 80% 이상 ( 초음파에서 50~69% 협착인경우 ) 이었다. 2502명 (1181 무증상협착 ; 1321 증상협착 ) 환자를추적기간중앙값 2.5 년동안관찰하였다. 무증상과증상경동맥협착환자를모두합쳐서분석하였을때일차결과변수의발생이스텐트설치군 7.2%, 수술군 6.8% 로두치료가차이가없는것으로결론을내렸다 (hazard ratio with stenting, 1.11; 95% CI, 0.81 to 1.51; p=0.51). 무증상경동맥협착환자만따로분석한결과경동맥혈관성혈 / 스텐트설치군과내막절제수술군사이에일차결과변수발생률은차이가없었다 (5.6% vs. 4.9%; hazard ratio, 1.17; 95% CI, 0.69 to 1.98; p=0.56). 뇌졸중발생만분석하였을때에도 30일이내모든뇌졸중과 30일에서 4년사이의동측뇌졸중발생이혈관성형 / 스텐트설치군 4.5%, 수술군 2.7% 로유의한차이가없었다 (hazard ratio, 1.86; 95% CI, 0.95 to 3.66; p=0.07). 30일에서 4년사이의동측뇌졸중발생도혈관성형 / 스텐트설치군 2.0%, 수술군 2.4% 로비슷하게낮아, 두치료모두효과가장기적으로잘유지되었다 (durability). 그러나혈관성형 / 스텐트설치술과수술을내과적치료와비교하지못한제한점이있으며, 연구진은내과적치료를하여도무증상경동맥협착에의한뇌졸중위험이높지않을가능성이있다고언급하였다. 증상협착과무증상협착전체환자를분석한결과, 혈관성형 / 스텐트설치군에서는뇌졸중발생이유의하게많았고, 경동맥내막절제술군에서는심근경색이더많이발생하였다. 그러나뇌졸중이심근경색에비해환자의삶의질을더악화시킨것을고려하면두치료가동등한효과를보였다는결론에대한비판이있다. 24 또한심근경색에는심전도의변화만있는경우도포함되었으나뇌졸중의경우에는일과성뇌허혈이포함되지않아형평성에문제가있다는비판도있다. 무증상경동맥협착군만분석하였을때에도유의하지는않았지만혈관성형 / 스텐트설치군에서뇌졸중발생이높고 ( 혈관성형 / 스텐트설치군 4.5% vs. 수술군 2.7%; hazard ratio, 1.86; 95% CI, 0.95 to 3.66; p=0.07), 수술군에서심근경색발생이높은경향을보였다 ( 혈관성형 / 스텐트설치군 1.2% vs. 수술군 2.2%; hazard ratio, 0.55; 95% CI, 0.22 to 1.38; p=0.20). 4. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial 5 60% 이상무증상경동맥협착을대상으로경동맥내막절제술시행군과비수술군을비교한 Asymptomatic Carotid Surgery J Korean Neurol Assoc Volume 30 No. 2, 2012 81
김한영김성림전평강현승강규식구자성박종무조용진한상원유경호나정호허지회권순억오창완배희준이병철윤병우홍근식 Trial (ACST-1) 14 연구의 10년장기예후에대한추적연구가 2010 년에발표되었다. 30개국, 126센터에서 3120 명의무증상경동맥협착환자를사망시점또는생존자에대해서는중앙값 9 년동안 (IQR 6~11 년 ) 추적관찰하였다. 무증상경동맥협착은초음파에서 60% 이상의협착과무작위배정 6개월이내에경동맥협착에의한허혈증상이없었던경우로정의하였다. 즉각경동맥내막절제술을시행한수술군 (median delay 1 month, IQR 0.3~2.5 month) 과내과적치료를지속한수술보류군을비교하였다. 무작위배정이후 1년과 5년이내에양군에서무증상경동맥협착에대해수술이시행된빈도는수술군 89.7% 와 92.1%, 그리고수술보류군에서는각각 4.8% 와 16.5% 였다. 수술을받은모든환자에서수술 30일이내뇌졸중또는사망발생률은 3.0% (95% CI 2.4~3.9) 였다. 수술 30일이후에발생한뇌졸중은첫 5년간수술군 4.1% vs. 수술보류군 10.0% 로 5.9% (95% CI 4.0~7.8) 의큰차이를보였고, 10년간은수술군 10.8% vs. 수술보류군 16.9% 로 6.1% (95% CI, 2.7~9.4) 의차이를보여수술군이수술보류군에비해서뇌졸중발생이상대적으로 46% (ratio of stroke incidence rates with CEA, 0.54; 95% CI, 0.43~0.68; p<0.0001) 유의하게감소하였다. 수술로인한뇌졸중또는사망을포함하여 (30일이내뇌졸중또는사망 +30 일이후뇌졸중 ) 장기적인이득을분석하여도, 첫 5년동안수술군 6.9% vs. 수술보류군 10.9% 로 4.1% (95%, CI 2.0~6.2) 의차이가있었고, 10년동안은수술군 13.4% vs. 수술보류군 17.9% 로 4.6% (95% CI, 1.2~7.9) 의차이를보여, 수술과연관된뇌졸중또는사망을고려하여도수술군의성적이우수하였다. 특히추적기간동안발생한 287 건의뇌졸중중절반이넘는 166 건이사망또는심각한장애를남기는뇌졸중이었는데, 수술한경우에서전체뇌졸중이감소한정도와비슷한정도로사망또는심각한장애를남기는뇌졸중이감소하였다. 발생부위가확인된뇌졸중을분석한결과, 경동맥협착동측의뇌졸중발생이가장크게감소하였다 (38 vs 92; Relative Risk, 0.43; 95% CI, 0.28~0.68). 그러나협착과관련이없는영역의뇌졸중도수술군에서유의하게감소하였다 (contralateral stroke 39 vs 64; vertebrobasilar stroke 11 vs 23). 추적관찰기간동안양군에서대부분의환자가항혈전제와항고혈압제를복용하였으며, 내과적치료에는차이가없었다. 아집단분석에서남녀모두에서, 그리고지 질강하치료 (lipid lowering therapy) 를한경우나그렇지않은경우에도수술의이득은유의하였다. 단 75세이상환자군은수술의이득이없었는데, 이는이환자의기대수명이낮은것과추적관찰기간중뇌졸중이외의다른원인으로사망한경우가많아수술효과가희석된것으로생각한다. 결론적으로 75세이하의환자에서무증상경동맥협착의내막절제술은 10년뇌졸중위험을감소시키는장기적인이득이있으며, 감소된뇌졸중의절반은장애를남기거나예후가매우불량한뇌졸중이었다. 하지만저자들은내과적치료가향상되고수술하지않은경동맥협착의뇌졸중위험도감소, 수술위험의변화, 환자의기대수명정도에따라경동맥내막절제술의이득을평가하도록추천하였다. 외국뇌졸중진료지침수정현황 먼저독자의혼돈을피하기위해진료지침마다권고안의권고수준과근거수준을결정하는체계가다르다는것을밝혀둔다. 2009 년제1판진료지침에서외국주요진료지침의권고안을정리하여소개할때는일관성을위해우리의진료지침권고안작성방식에맞추어외국권고안의권고수준과근거수준을변경하였다 (Table 2). 그러나아래에소개되는외국주요진료지침의개정된권고안의권고수준과근거수준은독자에게원문의내용을충실히전달하기위해각진료지침에서사용하는방식을그대로사용하였다. 본문중에간단히내용을소개하고는있으나, 독자가참고문헌을이용하여각진료지침의자세한근거수준과권고수준결정방식을이해하는것이필요하다. 1. 2008 년 ESO 뇌졸중진료지침의개정사항 (Table 3) 9 2003년 ESO 진료지침에서는 60~99% 의무증상경동맥협착을가진환자중일부는경동맥내막절제술이필요하다 ( 근거수준 Level II, intermediate level of evidences from small randomized trials or predefined secondary endpoints of large randomized controlled trials; 2003 년 ESO 진료지침은권고안에권고수준을부여하지않고근거수준만부여하였음 ) 라고권고하였었는데, 25 2008 년에는 뇌졸중발생이고위험군 Table 3. Recent updates of 2008 ESO guideline for asymptomatic carotid stenosis 9 1. Carotid surgery is not recommended for asymptomatic individuals with significant carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial NASCET 60~99%), except in those at high risk of stroke (Class I, Level C). 2. Carotid angioplasty, with or without stenting, is not recommended for patients with asymptomatic carotid stenosis (Class IV, GCP). 3. It is recommended that patients should take aspirin before and after surgery (Class I, Level A). 82 대한신경과학회지제 30 권제 2 호, 2012
인환자를제외하고는수술적치료를권장하지않는다 ( 권고수준 Level C, 근거수준 Class I; 2008 년 ESO 진료지침은적절하게설계된임상시험에서나온결과에근거수준 Class I을부여하며, 근거수준이 Class I인경우에는권고수준 Level A를부여하는것을원칙으로하고있으므로, 이권고안은권고수준 Level A가맞을것으로생각하나진료지침에는 Level C로기술되어있어오류일것으로판단함 ) 로변경하였다. 이러한개정의근거는무증상경동맥협착에대한수술이내과적치료에비하여동측뇌졸중의상대적위험도는 (relative risk reduction) 0.47~0.54로낮지만절대적이득은일년에약 1% 로작은것에비해수술로인한뇌졸중과사망이 3% 인것을고려한것이다. 기대수명이 5년이상이며 80% 이상무증상협착이있는남자는고위험군에해당하며수술과연관된합병증이 3% 미만인센터에서수술을받는경우에이득이있다고기술하고있다. 경동맥혈관성형술에대해서는스텐트설치술동반시행유무와상관없이 일반적으로권고하지않는다 (is not routinely recommended; 근거수준은부여되어있지않음 ) 에서 권고하지않는다 (is not recommended; 권고수준 GCP [good clinical practice], Class IV evidence but recommended best practice based on the experience of the guideline development group; 근거수준 Class IV, evidence from uncontrolled studies, case series, case reports, or expert opinion) 로권고안을개정하였다. 그러나 2008 년 ESO 진료지침은 CREST 연구결과가발표되기전에나온것이다. 2. 2010 년 AHA/ASA 뇌졸중일차예방진료지침의개정사항 (Table 4) 3 수술관련이환율과사망률이 3% 미만인경우에예방적경동맥내막절제술이신중하게선택된환자에서추천될수있다는내용의권고안이권고수준 Class I (benefit >>> risk, treatment should be performed), 근거수준 Level of Evidence A (LoE A, multiple populations evaluated from multiple randomized trials or meta-analysis) 에서 26 근거수준은 LoE A로동일하나권고수준은 Class IIa (benefit >> risk, it is reasonable to perform treatment) 로낮아졌다. 또한최근내과적치료의발전이반영된연구결과에의하면이러한예방적경동맥내막절제술에의한이득이예상보다적을수있으며, 3% 미만이라는기존의수술관련합병증발생기준이높은것일수있다는기술이추가되었다. 예방적혈관성형 / 스텐트설치술에대해서는예방적경동맥내막절제술과마찬가지로매우선택적인환자에게고려할수있다는내용이추가되었다 (Class IIb, benefit risk, treatment may be considered; LoE B, limited population evaluated from a single randomized trial or nonrandomized studies). 그러나경동맥내막절제술이임상시험을통해내과적치료에비해우월한것이입증되었던반면에, 혈관성형 / 스텐트설치술과내과적치료를비교한임상시험이없었기때문에, 내과적치료에비해혈관성형 / 스텐트설치술의우월성은아직확립되지않았다는내용이추가로기술되어있다. 또한 경동맥내막절제술의고위험군환자에대해서경동맥혈관성형 / 스텐트설치술이대안일수있다 는권고안도권고수준은 Class IIb로동일하지만근거수준을 LoE B에서 Table 4. 2010 AHA/ASA guideline update for asymptomatic carotid stenosis 3 1. Patients with asymptomatic carotid artery stenosis should be screened for other treatable risk factors for stroke with institution of appropriate lifestyle changes and medical therapy (Class I, Level of Evidence C). 2. Selection of asymptomatic patients for carotid revascularization should be guided by an assessment of comorbid conditions and life expectancy, as well as 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). 3. The use of aspirin in conjunction with CEA is recommended unless contraindicated because aspirin was used in all of the cited trials of CEA as an antiplatelet drug (Class I, Level of Evidence C). 4. Prophylactic CEA performed with <3% morbidity and mortality can be useful in highly selected patients with an asymptomatic carotid stenosis (minimum 60% by angiography, 70% by validated Doppler ultrasound) (Class IIa, Level of Evidence A). It should be noted that the benefit of surgery may now be lower than anticipated based on randomized trial results, and the cited 3% threshold for complication rates may be high because of interim advances in medical therapy. 5. Prophylactic carotid artery stenting might be considered in highly selected patients with an asymptomatic carotid stenosis (>60% on angiography, >70% on validated Doppler ultrasonography, or >80% on computed tomographic angiography or MRA if the stenosis on ultrasonography was 50% to 69%). The advantage of revascularization over current medical therapy alone is not well established (Class IIb, Level of Evidence B). 6. The usefulness of CAS as an alternative to CEA in asymptomatic patients at high risk for the surgical procedure is uncertain (Class IIb, Level of Evidence C). 7. Population screening for asymptomatic carotid artery stenosis is not recommended (Class III, Level of Evidence B). J Korean Neurol Assoc Volume 30 No. 2, 2012 83
김한영김성림전평강현승강규식구자성박종무조용진한상원유경호나정호허지회권순억오창완배희준이병철윤병우홍근식 Table 5. 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease 10 1) In asymptomatic patients with known or suspected carotid stenosis, duplex ultrasonography, performed by a qualified technologist in a certified laboratory, is recommended as the initial diagnostic test to detect hemodynamically significant carotid stenosis (Class I, Level of Evidence C). 2) It is reasonable to perform duplex ultrasonography to detect hemodynamically significant carotid stenosis in asymptomatic patients with carotid bruit (Class IIa, Level of Evidence C). 3) It is reasonable to repeat duplex ultrasonography annually by a qualified technologist in a certified laboratory to assess the progression or regression of disease and response to therapeutic interventions in patients with atherosclerosis who have had stenosis greater than 50% detected previously. Once stability has been established over an extended period or the patient s candidacy for further intervention has changed, longer intervals or termination of surveillance may be appropriate (Class IIa, Level of Evidence C). 4) Duplex ultrasonography to detect hemodynamically significant carotid stenosis may be considered in asymptomatic patients with symptomatic PAD, coronary artery disease (CAD), or atherosclerotic aortic aneurysm, but because such patients already have an indication for medical therapy to prevent ischemic symptoms, it is unclear whether establishing the additional diagnosis of ECVD in those without carotid bruit would justify actions that affect clinical outcomes (Class IIb, Level of Evidence C). 5) Duplex ultrasonography might be considered to detect carotid stenosis in asymptomatic patients without clinical evidence of atherosclerosis who have 2 or more of the following risk factors: hypertension, hyperlipidemia, tobacco smoking, a family history in a first degree relative of atherosclerosis manifested before age 60 years, or a family history of ischemic stroke. However, it is unclear whether establishing a diagnosis of ECVD would justify actions that affect clinical outcomes (Class IIb, Level of Evidence C). 6) Carotid duplex ultrasonography is not recommended for routine screening of asymptomatic patients who have no clinical manifestations of or risk factors for atherosclerosis (Class III, Level of Evidence C). 1) Antihypertensive treatment is recommended for patients with hypertension and asymptomatic extracranial carotid or vertebral atherosclerosis to maintain blood pressure below 140/90 mm Hg (Class I, Level of Evidence A). 2) Patients with extracranial carotid or vertebral atherosclerosis who smoke cigarettes should be advised to quit smoking and offered smoking cessation interventions to reduce the risks of atherosclerosis progression and stroke (Class I, Level of Evidence B). 3) Treatment with a statin medication is recommended for all patients with extracranial carotid or vertebral atherosclerosis to reduce low-density lipoprotein (LDL) cholesterol below 100 mg/dl (Class I, Level of Evidence B). 4) If treatment with a statin (including trials of higher dose statins and higher-potency statins) does not achieve the goal selected for a patient, intensifying LDL-lowering drug therapy with an additional drug from among those with evidence of improving outcomes (ie, bile acid sequestrants or niacin) can be effective (Class IIa, Level of Evidence B). 5) For patients who do not tolerate statins, LDL-lowering therapy with bile acid sequestrants and/or niacin is reasonable (Class IIa, Level of Evidence B). 6) Diet, exercise, and glucose-lowering drugs can be useful for patients with diabetes mellitus and extracranial carotid or vertebral artery atherosclerosis. The stroke prevention benefit, however, of intensive glucose lowering therapy to a glycosylated hemoglobin A1c level less than 7.0% has not been established (Class IIa, Level of Evidence A). 7) Administration of statin-type lipid-lowering medication at a dosage sufficient to reduce LDL cholesterol to a level near or below 70 mg/dl is reasonable in patients with diabetes mellitus and extracranial carotid or vertebral artery atherosclerosis for prevention of ischemic stroke and other ischemic cardiovascular events (Class IIa, Level of Evidence B). 8) Antiplatelet therapy with aspirin, 75 to 325 mg daily, is recommended for patients with obstructive or nonobstructive atherosclerosis that involves the extracranial carotid and/or vertebral arteries for prevention of MI and other ischemic cardiovascular events, although the benefit has not been established for prevention of stroke in asymptomatic patients (Class I, Level of Evidence A). 9) Antiplatelet agents are recommended rather than oral anticoagulation for patients with atherosclerosis of the extracranial carotid or vertebral arteries with (Class I, Level of Evidence B) or without (Class I, Level of Evidence C) ischemic symptoms. 1) 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). 2) 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). 3) 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). 4) 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). LoE C (very limited population evaluated) 로낮추어 경동맥내막절제술의고위험군환자에대해서수술대신혈관성형 / 스텐트설치술을시행하는것에대한유용성은불명확하다 로변경되었다. 또한무증상경동맥협착에대한스크리닝검 사는추천되지않는다는내용이추가되었다 (Class III, no benefit or harm, treatment is not useful and may be harmful; LoE B). 84 대한신경과학회지제 30 권제 2 호, 2012
3. 2011 년 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/ CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS 두개외경동맥및경추동맥질환환자의진료지침 (Table 5) 10 최근미국심장학회, 뇌졸중학회, 신경간호학회, 신경외과학회, 영상의학학회, 혈관의학회같은여러학회공동으로발표한두개외경동맥과경추동맥질환환자의진료지침중에서무증상경동맥협착에관한내용을요약하면다음과같다. 1) 진단먼저진단과관련된내용에서는, 무증상두개외경동맥협착이있거나또는의심되는환자에서는경동맥초음파검사를우선적인진단검사로추천한다 ( 권고수준 Class I, 근거수준 LoE C). 경동맥잡음이들리는무증상환자에게서경동맥협착여부를알기위해서경동맥초음파검사를하는것이적절하다 (Class IIa, LoE C). 50% 이상의경동맥협착환자에서매년경동맥초음파검사를하는것은적절하며, 일단더이상의진행이없으면추적검사간격을늘리거나추적검사를종료할수있다 (Class IIa, LoE C). 말초동맥협착증, 관상동맥질환, 동맥경화성대동맥류가있는환자와고혈압, 고지혈증, 흡연, 부모또는형제중 60 세이전에동맥경화증이발병한경우, 허혈뇌졸중의가족력같은위험인자중에서 2가지이상의위험인자가있는환자에게경동맥협착발견을위한초음파검사를고려할수있다 (Class IIb, LoE C). 동맥경화의위험요인이없거나뇌허혈증상과관련이없는신경계환자에게스크리닝을위해경동맥초음파검사는추천하지않는다 (Class III, LoE C). 그러나이러한권고안은미국의의료환경을고려한것이며, 국내의상황은경동맥초음파검사가임의비급여항목이며다른 영상의학검사와비교해서비용효과측면에서그다지우월하지않다는것을고려하여야한다. 2) 내과적치료무증상경동맥협착에대한내과적치료에관한권고안을정리하면다음과같다. 고혈압이있는무증상경동맥협착환자에서는 140/90 mmhg 미만을유지하기위한항고혈압치료가추천된다 (Class I, LoE A). 금연이추천된다 (Class I, LoE B). LDL 콜레스테롤을 100 mg/dl 미만으로낮추기위한스타틴치료가추천된다 (Class I, LoE B). 스타틴단독치료로 LDL 콜레스테롤강하효과가미미하거나, 스타틴을사용할수없는경우, bile acid sequestrants 또는 niacin 을추가또는대신사용할수있다 (Class IIa, LoE B). 당뇨가있는환자에서식이요법, 운동요법, 혈당강하제복용과 LDL 콜레스테롤을 70 mg/dl 미만으로낮추기위하여스타틴치료를하는것은적절하다 (Class IIa, LoE B). 뇌졸중예방효과는확실하지않으나, 심근경색또는다른허혈성심혈관질환을예방하기위해매일아스피린 75~325 mg 복용을추천한다 (Class I, LoE A). 항응고제보다는항혈소판제제를추천한다 (Class I, LoE C). 3) 경동맥내막절제술또는혈관성형 / 스텐트설치술무증상경동맥협착환자에서동반질환, 기대수명, 기타요인을고려하여혈관성형 / 스텐트설치술과내막절제술대상환자를선별해야한다. 내막절제술과혈관성형 / 스텐트설치술의이득과위험도에대해환자와충분히상의하고환자의선호도를고려해야한다 (Class I, LoE C). 수술에의한뇌졸중, 심근경색, 사망의위험이낮다면, 70% 이상의무증상경동맥협착에서내막절제술을시행하는것이적절하다 (Class IIa, LoE A). 경동맥혈 Table 6. Updated Korean Guidelines for Asymptomatic Carotid Stenosis Management 1. 무증상경동맥협착환자에서뇌졸중의치료가능한위험인자를조사하여동반된위험인자를집중적으로치료해야한다. 1) 고혈압이동반된경우, 140/90 mmhg 미만을유지하기위한혈압강하치료가필요하다 ( 근거수준 Ia, 권고수준 A). 2) 흡연자는적극적으로금연치료를시행해야한다 (GPP). 3) LDL 콜레스테롤을 100 mg/dl 미만으로낮추기위한스타틴치료가필요하다 ( 근거수준 Ia, 권고수준 A). 4) 당뇨가동반된경우, 식이요법, 운동요법, 약물요법등을통한엄격한혈당조절이전체심뇌혈관질환의예방을위해필요하다 ( 근거수준 Ia, 권고수준 A). 2. 50% 이상의무증상경동맥협착환자에서금기사항이없는한항혈소판제제치료가권장된다 ( 근거수준 IIa, 권고수준 B). 50% 미만인환자에서항혈소판제제치료는동반된위험인자와출혈부작용위험을고려하여결정하는것이바람직하다 (GPP). 3. 60-99% 무증상경동맥협착에서수술관련합병증이 3% 미만인경우예방적경동맥내막절제술또는혈관성형 / 스텐트설치술을고려할수있다 ( 경동맥내막절제술 : 근거수준 Ia, 권고수준 A; 혈관성형 / 스텐트설치술 : 근거수준 IIb, 권고수준 B). 수술대상환자의선택에있어동반된질환, 기대여명, 환자의선호도와기타개인별요인들을신중하게고려하고치료에따른이득과위험에대해충분한상의가필요하다. 경동맥내막절제술의이득은내과적치료의발전으로과거에비해감소했을가능성이있어, 수술관련합병증에대한 3% 기준을낮추는것을고려할수있다. 경동맥내막절제술과달리혈관성형 / 스텐트설치술의경우내과적치료와직접비교한연구결과는없다. 4. 수술이필요한 60-99% 무증상경동맥협착환자에서경동맥내막절제술의수술위험성을높이는동반질환이있는경우경동맥혈관성형 / 스텐트설치술을고려할수있다 ( 근거수준 IIa, 권고수준 B). 그러나수술고위험군에서혈관성형 / 스텐트설치술과내과적치료를직접비교한연구결과는없다. J Korean Neurol Assoc Volume 30 No. 2, 2012 85
김한영김성림전평강현승강규식구자성박종무조용진한상원유경호나정호허지회권순억오창완배희준이병철윤병우홍근식 관성형 / 스텐트설치술은무증상경동맥협착환자중에서아주선택적으로고려할수있으나, 내과적치료에비해우월한지는아직확립되어있지않다 (Class IIb, LoE B). 또한동반된질환으로수술또는혈관성형 / 스텐트설치술합병증위험이높은환자에서내과적치료에대한수술또는시술의우월성은아직확립되어있지않다 (Class IIb, LoE B). 뇌졸중일차예방을위한무증상경동맥협착의국내진료지침의개정내용 (Table 6) 과거경동맥협착임상시험이시행될당시의내과적치료에비하여최근의내과적치료는위험인자관리와새로운약물치료의개발로많은발전이있었다. 따라서경동맥내막절제술이나혈관성형 / 스텐트설치술의이득이과거연구결과에비해감소하였을가능성이있다. 지난 25년간발표된연구를분석한결과무증상경동맥협착에의한뇌졸중발생이감소하고있어서, 경동맥내막절제술또는혈관성형 / 스텐트설치술에비해안전하고경제적인내과적치료의중요성이강조되고있다. 개정된 ESO 와 AHA/ASA 진료지침과같이국내뇌졸중진료지침에도내과적치료의중요성을반영할필요가있다. 하지만내과적치료가발전함과동시에 patch angioplasty 와같은경동맥내막절제술의발전과 embolic protection device 도입같은혈관성형 / 스텐트설치술의발전에의해수술또는시술치료의성적도향상되고있음을동시에고려하여야한다. 또한최근발표된 ASCT-1 10년추적연구결과 5 스타틴사용유무와상관없이내과적치료에비해경동맥내막절제술의우월한뇌졸중예방효과가장기적으로도유효한것이입증되었지만, 2008 년 ESO 와 2010 년 AHA/ASA 진료지침개정에는이연구결과를고려하지않았다. 새로운근거와외국의개정된진료지침을고려하여무증상경동맥협착환자에서고혈압, 흡연, 이상지질혈증, 당뇨같은다른뇌졸중위험인자에대한내과적치료의중요성을강조하기위하여 2009 년제1판진료지침에비해보다구체적으로기술하였다. 항혈소판제치료에대해서는새로운근거가없는것으로판단하여기존의권고안을유지하였다. 무증상경동맥협착에서비록내과적치료법의발전으로뇌졸중발생률이감소하였지만내과적치료와비교한장기적인경동맥내막절제술효과를고려하여, 기대수명 5년이상의뇌졸중위험이높은 60~99% 무증상경동맥협착군에서수술관련합병증이 3% 미만인경우경동맥내막절제술의권고수준을기존과동일하게유지하였다 ( 근거수준 Ia, 권고수준 A). 그러나최근내과적치료에따른뇌졸중발생감소를고려하여수술관련합 병증 3% 기준을낮추는것을고려할필요가있다는기술을추가하였다. 경동맥혈관성형 / 스텐트설치술의경우한임상시험에서경동맥내막절제술과동등한효과를보여경동맥내막절제술과함께기술하였지만, 증상성협착환자도포함한연구였으며삶의질에영향이더큰뇌졸중의발생이혈관성형 / 스텐트설치군에서더높았던점, 그리고내과적치료와직접적인비교를시행한연구결과가아직없으며, 내과적치료군에서뇌졸중발생이감소하고있는점을고려하여근거수준과권고수준을경동맥내막절제술보다낮게기술하였다 ( 근거수준 IIb, 권고수준 B). 또한경동맥내막절제술위험이높은환자에서혈관성형 / 스텐트설치술에대한권고수준은이전과동일하게유지하였다 ( 근거수준 IIa, 권고수준 B). 그러나스텐트설치술은내과적치료와직접비교한연구가없음을권고안에추가하였다. 국내의경우대부분의센터가미국이나유럽에비해경동맥내막절제술의시행빈도가낮고, 스텐트설치술경험은상대적으로높다. 따라서경동맥내막절제술과스텐트설치술의선택을결정할때국내상황을고려할필요가있다. REFERENCES 1. O'Leary DH, Polak JF, Kronmal RA, Kittner SJ, Bond MG, Wolfson SK Jr, et al. Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group. Stroke 1992;23:1752-1760. 2. Fine-Edelstein JS, Wolf PA, O'Leary DH, Poehlman H, Belanger AJ, Kase CS, et al. Precursors of extracranial carotid atherosclerosis in the Framingham Study. Neurology 1994;44:1046-1050. 3. Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, et al. Guidelines for the primary prevention of stroke. A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:517-584. 4. Clinical Research Center for Stroke. Clinical Practice Guideline for Stroke. 1st ed. 2009. (www.cpg.or.kr/files/guideline/1256711648554.pdf). Accessed 03/21/2012. 5. Halliday A, Harrison M, Hayter E, Kong X, Mansfield A, Marro J, et al. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet 2010;376:1074-1084. 6. Brott TG, Hobson RW 2nd, Howard G, Roubin GS, Clark WM, Brooks W, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010;363:11-23. 7. Abbott AL. Medical (nonsurgical) intervention alone is now best for prevention of stroke associated with asymptomatic severe carotid stenosis: results of a systematic review and analysis. Stroke 2009;40: e573-e583. 8. Marquardt L, Geraghty OC, Mehta Z, Rothwell PM. Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population-based study. Stroke 2010;41:e11-e17. 86 대한신경과학회지제 30 권제 2 호, 2012
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