08-성동연

KOR J CEREBROVASCULAR SURGERY December 2OO7 Vol. 9 No 4, page 271-6 경동맥혈관성형술및스텐트삽입술을시행받은환자의 30 일간의임상경과 : 임상연구 성균관대학교의과대학강북삼성병원신경외과 1, 신경과 2, 영상의학과 3 성동연 1 유장선 1 원유삼 1 권영준 1 양재영 1 최천식 1 김용범 2 김병문 3 Thirty-day Clinical Outcomes of Carotid Artery Stenting Patients with Symptomatic and Asymptomatic Carotid Artery Stenosis : Clinical Research Dong Yeon Sung, MD 1, Jang Seon You, MD 1, Yu Sam Won, MD 1, Young Joon Kwon, MD 1, Jea Young Yang, MD 1, Chun Sik Choi, MD 1, Yong Bum Kim, MD 2, Byung Moon Kim, MD 3 Department of Neurosurgery 1, Neurology 2, Radiology 3, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea ABSTRACT Objective : Recently, carotid artery stenting (CAS) has become as the first choice of treatment for carotid artery stenosis. Although there are many differences in the outcomes of patients receiving stents among many different study groups, some reports suggest that stenting can be performed with periprocedural complication rates similar to those of a carotid endarterectomy (CEA). In this study, we investigated 39 cases of CAS. Methods : From May 2003 to March 2007, 39 patients undergoing CAS were reviewed. We analyzed the 30-day morbidity/mortality rate. A minor stroke was defined as a new neurological deficit that either resolved completely within 30 days or increased the NIH Stroke Scale by 3. A major stroke was defined as a new neurological deficit that persisted for 30 days and increased the NIH Stroke Scale by 4. Results : Among 39 patients, a minor stroke was noted in three patients (7.7%), and there were no major strokes and deaths. The overall 30-day stroke and death rate was 7.7% (n = 3). Conclusion : With the evolution and maturation of equipment and technique, carotid angioplasty and stenting (CAS) is increasingly being used for the treatment of carotid artery disease. (Kor J Cerebrovascular Surgery 9(4):271-6, 2007) KEY WORDS : Carotid artery Stent Angioplasty Carotid endarterectomy 서 1980년대후반 NASCET (North American Symptomatic Carotid Endarterecto-my Trial) 의연구결과에서약물치료에비해 CEA의치료성적이우월함이보고된 논문접수일 : 2007 년 10 월 12 일심사완료일 : 2007 년 11 월 19 일교신저자 : Jang Seon You M.D. Department of Neurosurgery, Kangbuk Samsung Hospital, 108, Pyung-dong, Jongro-gu, Seoul, Korea, 110-746 전화 : (02) 2001-2158 전송 : (02) 2001-2157 E-mail : jsisid@hanmail.net 론 이후 CEA는최근까지경동맥협착증의표준적인치료로서시행되어왔다. 1) 하지만전신마취와수술로인한합병증 (perioperative complication) 및병변의해부학적위치에따라시술에제한이따르는등의단점이있다. CAS는 1980년대초시행되기시작하여 CEA의대안적치료로선택되었다. 2) 초기에는재협착, 시술중색전등의시술부작용 (major adverse event) 을보였으나 3) 최근기술및장비의발전과더불어점차좋은치료결과를보이고있으며현재급속하게 CEA를대체해나가고있다. 치료결과의비교연구에서도 CEA와대등하거나일부우월한성적을보이고있 고 4)5) 현재도이에대한여러그룹들의대규모무작위전향적 연구들이진행되고있어그결과에관심이집중되고있다. 6) 271

경동맥혈관성형술및스텐트삽입술을시행받은환자의 30 일간의임상경과 : 임상연구 대상및방법 2003년 5월부터 2007년 3월까지숙련된단일시술자에의해 CAS를시행받은 39명의환자 (39 arteries) 를대상으로하였다. 시기별시술건수는 2003년에 4례 2004년에 5례 2005년에 6례 2006년에 18례이었고 2007년에는 3월까지 6례이었다. 시술중색전예방장비 (embolic protection device, EPD) 를사용한경우가 31례 (79.5%) 였다. 시술후 24 시간이내확산강조영상 (Diffusion Weighted Image, DWI) 을시행한경우가 35례였고이중 33례는시술전 24시간이내에도 DWI를시행하여시술전후의영상비교가가능하였다. 협착의정도는혈관조영영상에서 NASCET 방법을 Table 1. Clinical characteristics No. of patients 39 Mean age 67.1 Male/Female ratio 28:11(71.9%:28.1%) Hypertension 27(69.2%) Diabetes 21(53.8%) Coronary heart disease 08(20.5%) Symptomatic CA lesion 34(87.2%) Stenosis ratio 85.1% symptomatic 85.5% asymptomatic 84.7% Lesion side right 24(61.5%) left 15(38.5%) 이용하여측정하였다. 시술의적응증은증상이있는경우경동맥협착이 50% 이상, 증상이없는경우협착이 70% 이상일때시행하는것을원칙으로하였다. 시술 48시간이전부터환자는매일 ticlopidine 500mg과 aspirin 325mg을복용하도록하였다. 국소마취하에쉘딩거법 (Sheldinger technique) 을이용하여우측대퇴동맥을통해경동맥으로의접근을시행하였고 6F또는 8F의 guiding catheter를사용하였다. 시술전헤파린 100IU/kg를정주하여시술중 ACT(activated clotting time) 가정상의 2.5~3배정도로유지되도록하였다. self expanding stent를사용하였으며 pre & poststenting baloon angioplasty를실시하였다. 시술에사용된 EPD는 FilterWire EZTM (Boston scientific Corp., Natick, MA) 19례, Spider RX (ev3, Plymouth, MN, USA) 8례, Emboshield filter protection systems (MedNova, Galway, Irelan) 4례, PercuSergeGuardWire system (Medtronic, Danvers, MA) 2례였다. 시술후 30일이내발생한 minor stroke, major stroke 및사망등을분석하였으며이중 minor stroke은시술후새로이발생한신경학적결손이 30일이내에완전히소실되거나 NIHSS의증가가 3 이하인경우로하였고 major stroke 은신경학적결손이 30일이후까지지속되고 NIHSS의증가 Table 2. Overall 30-day morbidity and mortality rate Minor stroke 3(7.7%) Major stroke 0 Death 0 Table 3. Characteristics of postprocedure stroke patients minor stroke Case1 Case2 Case3 Age/Sex 68/M 68/M 70/M Preprocedure symptom - dysarthria - Systemic complication HTN, DM HTN, DM HTN Preprocedure DWI senile change Lt. pons infarct Lt. ant. thalamic and PCA infarct Side left left left Stenisis ratio 90% 85% 86% Protection yes yes no New lesion in post procedure DWI + + + dysarthria dysarthria Postprocedure neurological worsening Lt hemifacial dysarthria memory numbness disturbance 272 Kor J Cerebrovascular Surgery 9(4):271-6, 2007

성동연 유장선 원유삼 권영준 양재영 최천식등 가 4 이상인경우로하였다. 결과 환자의평균나이는 67.1(39~84) 세였고남자가 28명 (71.9%) 여자가 11명 (28.1%) 이었다. 시술당시고혈압의병 력이있었던환자는 27명 (69.2%), 당뇨가있던환자는 21명 (53.8%), 고혈압과당뇨가모두있던환자는 17명 (43.6%) 이 었고심장질환병력이있던환자는 8명 (20.5%) 이었다. 시술 전심각한호흡기질환이있던환자는없었다. 고지혈증 (total cholesterol>240mg/dl 또는 triglyceride>200mg/dl) 을보 Table 4. New DWI lesions and stroke after CAS according to treatment EPD(+) EPD(-) No. of case 31 8 Post procedure DWI 29 6 New lesion in post procedure DWI 19(65.5%) 5(83.3%) Minor stroke 2(6.5%) 1(12.5%) 인환자는 10명 (25.6%) 이었고평균콜레스테롤수치는 188(106~316)mg/dl, triglyceride는 150.2(72~541)mg/dl, LDL은 115.9(50~190.3)mg/dl, HDL은 43.1(31~67)mg/dl 였다. 흡연자는 21명 (53.8%) 이었다. 시술전증상이있던환자가 34명 (87.2%), 증상이없던환자는 5명 (12.8%) 이었다. 증상은안정화된뇌경색이 23례, 일과성허혈발작 (TIA) 이 7례, 두통및어지럼증등의비특이적증상이 4례였다. 시술대상경동맥은우측이 24례 (61.5%) 좌측이 15례 (38.5%) 였고시술대상이된경동맥의협착률은증상이있는환자에선 85.5(60~99)%, 무증상환자에서는 84.7(70~99)% 로평균 85.1% 였다. 전체환자중 5명의환자에서시술대상반대편의경동맥에 70% 이상의협착을보였다 (Table 1). 모든환자에서시술은성공적으로시행되었고시술도중합병증의발생은없었다. 시술후 30일간의경과에서시술전증상이있던 34명의환자중일과성허혈발작환자 7명은이후증상의재발은없었다. 뇌경색을보인 23명의환자중 1례에서증상의악화소견을보였고증상이없던 5명의환자중 2 례에서시술후새로운증상이발생하였다. 시술후신경학적 Table 5. Carotid artery stent registries Registry N Stent EPD Comments * ARCHeR 581 Acculink Accunet 30 days MI/stroke/D 8.3% * 1 yr stroke/d 9.6% BEACH 480 Wallstent FilterWire 30 days MI/stroke/D 5.8% * 1 yr MI/stroke/D 9.1% CABERNET 454 NexStent FilterWire 30 days MI/stroke/D 3.8% 1 yr MI/stroke/D 4.5% CAPTURE 2,500 RX Acculink Accunet 30 days MI/stroke/D 5.7% CaRESS 143 Wallstent Guardwire Plus 30 days stroke/d 2.1% CREATE Pivotal 419 Protege SPIDER OTW 30 days MI/stroke/D 6.2% * CREATE SpideRx 125 Acculink SpideRx 30 days MI/stroke/D 5.6% CREST 749 RX Acculink RX Accunet 30 days stroke/d 4.4% MAVErIC I 99 Exponent GuardWire 30 days MI/stroke/D 5.1% MAVErIC II 399 Exponent GuardWire 30 days MI/stroke/D 5.3% MO.MA 157 Any MO.MA 30 days stroke/d 5.7% PRIAMUS 416 Any MO.MA 30 days stroke/d 4.6% SECuRITY 398 Xact Carotid Stent Emboshield 30 days MI/stroke/D 8.5% * Indicates data published in peer review journals. Otherwise, data have been presented in international meetings, but not subjected to careful peer review. ARCHeR = Acculink for Revascularization of Carotids in High-Risk Patients; BEACH = Boston Scientific EPI: A Carotid Stenting Trial for High Risk Surgical Patients; CABERNET = Carotid Artery Revascularization using Boston Scientific EPI Filterwire EX/EZ and the EndoTex NexStent; CAPTURE = Carotid Acculink/Accunet Post Approval Trial to Uncover Rare Events; CaRESS = Carotid Revascularization using Endarterectomy or Stenting Systems; CREATE = Carotid Revascularization with ev3 Arterial Technology Evaluation; CREST = Carotid Revascularization Endarterectomy versus Stent Trial; d = days; D = death; EPD embolic protection device; MAVErIC = Endarterectomy Versus Angioplasty in Patients with Severe Symptomatic Carotid Stenosis; MI = myocardial infarction; MO.MA = Multicenter Registry to Assess the Safety and Efficacy of the MO.MA Cerebral Protection Device During Carotid Stenting; SECuRITY = Registry Study to Evaluate the NeuroShield Bare Wire Cerebral Protection System and X-Act Stent in Patients at High Risk for Carotid Endarterectomy Kor J Cerebrovascular Surgery 9(4):271-6, 2007 273

경동맥혈관성형술및스텐트삽입술을시행받은환자의 30 일간의임상경과 : 임상연구 악화소견을보인 3명중 1명은곧바로회복되어퇴원시신경학적결손이없었고나머지 2명은호전되는양상을보였으나시술 30일경과후에도증상은경미하게지속되었다. 세명의환자모두전술한 stroke의분류기준에따라 minor stroke 에해당되었으며 7.7% 의발생률을보였다. 시술과관련된사망이나시술후 30일이내사망한환자는없었다 (Table 2). Stroke이발생한첫번째환자 (Case1) 는시술직후수일간경도의구음장애와좌측안면부의감각저하및미각의저하를호소하였으며시술후시행한 DWI에서양측대뇌피질에여러개의작은색전이확인되었다. 증상은점차호전되어퇴원시에는신경학적결손없이완전히회복되었다. 두번째환자 (Case2) 는시술후구음장애가현저하게악화되었고 DWI 에서는좌측기저핵의앞쪽부위에새로운경색이발생하였다. 환자의증상은점차호전이되었으나시술 30일이후에도경미하게지속되었다. 세번째환자 (Case3) 는시술후구음장애, 기억장애, 어지럼증을보였고시술후확인한 DWI에서뇌량팽대 (callosal splenium) 와좌측설회 (Lt. lingual gyrus) 에색전이발견되었다. 증상은지속되어 30일이경과해도완전히호전되지는않았다 (Table 3). 본연구에서는 39건의시술중 31건에서 EPD (embolic protecti-ion device) 를사용하였으며이중시술후 DWI를시행한경우가 29례였고여기서새로운병변이확인된경우는 19례 (65.5%) 였다. EPD를사용하지않은 8례중시술후 DWI를시행한경우는 6례이고이중 5례 (83.3%) 에서시술후새로운병변이확인되었다. 또한EPD를사용하지않은 8례중 1례 (12.5%) 에서 minor stroke이발생하였고 EPD를사용한경우엔 2례 (6.5%) 의 minor stroke이발생하였다 (Table 4). 고찰 NASCET의연구에서증상이있는경동맥의중증협착 (70~99%) 환자에서 CEA가비수술적치료보다성적이우월하다는것이입증되면서 CEA는표준적인치료로자리를 잡았다. 1) 하지만수술로인한합병증을줄일수있다는점과덜침습적이라는장점으로인해최근 CAS시술이급격하게늘고있는추세이며, 이와더불어치료성적에대해많은연구결과가발표되었고현재도연구가진행중이다. 6) CEA의경우 NASCET1) 과 ACAS (Asymptomatic Carotid Artherosclerosis Stu-dy) 9) 의연구에서수용가능한 30일간의이병률및사망률 (acceptable 30-day morbidity/mortality rate) 을증상이있는경우 6% 미만, 증상이없는경우 3% 미만으로제시하였고 AHA (American Heart Association) 에서는시술로인해발생이예상되는 stroke 및사망률이증상이있는 50%~99% 협착환자에서는 6% 이상, 무증상이며협착률 60~99% 인환자에서는 3% 이상, 재시술은 10% 이상일경우비수술적치료를권고하였다. 10) CAS에대해서는아직까지시술에따른허용가능한이병률및사망률에대해명확히제시된바가없고 11) 최근여러연구그룹들에서보고한 CAS의 30일간의이병률및사망률 (death, stroke, MI) 은 3.8% 에서 8.5% 까지다양하다 (Table 5). 6-8) Wholey등은세계적인자료수집을통해 CAS의기술적성공률 (technical success rate) 은 98.4% 로보고하였고 30 일간의이병률및사망률을 5.07% (minor stroke rate 2.72%, major stroke rate 1.49%, mortality rate 0.86%) 로보고하였다. 14) 본연구에서도 30일간이병률및사망률이 7.7% 로기존의여러연구와비슷한결과를보였다. 그러나대부분의다른연구에서는 CEA고위험군을대상으로하였고시술중 EPD를사용하였지만본연구에서는시술대상의선택이무작위적으로이루어져 CEA고위험군 6) (80세이상 4명, Class III 협심증 1 명, 관상동맥질환 3명 ) 은 8명만포함된점과 8례에서는 EPD 를사용하지않았다는점에서수치의절대비교에는무리가있을것으로보인다. EPD 사용군에서발생빈도가낮기는했지만사용여부에관계없이시술후 DWI상새로운병변과 minor stroke환자가발생하였다. EPD사용유무에따른 CAS의성적비교에대한무작위연구는보고된바는없지만대체적으로 EPD의유 Table 6. High-risk criteria for CEA Anatomical criteria Lesion at C-2 or higher Lesion below clavicle Prior radical neck surgery or radiation Contralateral carotid occlusion Prior ipsilateral CEA Contralateral laryngeal nerve palsy Tracheostoma Medical comorbidity Age 80 yrs Class III/IV congestive heart failure Class III/IV angina pectoris Left main 2 vessel coronary disease Urgent(<30 days) heart surgery LV ejection fraction 30% Recent (<30 days) myocardial infaction Severe chronic lung disease Severe renal disease 274 Kor J Cerebrovascular Surgery 9(4):271-6, 2007

성동연 유장선 원유삼 권영준 양재영 최천식등 용성은인정을받고있다. 원위부 (distal) EPD와근위부 (proximal) EPD는각각의장단점을가지고사용되고있지만어느것도완벽한색전보호기능을가지고있지못하며오히려기구자체에의한혈관손상이나혈류방해로인한허혈을초래할수도있어이의일상적사용에대한타당성검증및지속적인장비의개발이필요하다. 6) 본연구에서는원위부 EPD 를사용하였고 2례의풍선형 (balloon type) 을제외하고모두필터형 (filter type) 이었다. EPD 사용에도불구하고색전이발생된원인으로는 guiding catheter 나 guidewire가병변을통과하면서색전이유발되었을가능성과필터의망사이또는 EPD와혈관벽의틈새로색전가루 (embolic debris) 가빠져나와색전을유발했을가능성등을생각해볼수있다. CAS는주로증상이있는 CEA 고위험군 (Table 6) 이적응대상이되어왔다. 2004년미국의 FDA와 2005년 CMS에서의규정에서도시술의대상을 CEA 고위험군에한정하고있다. 따라서그이외의대상, 즉 80% 이상의협착에무증상인환자또는 CEA 고위험군이아닌환자에서의치료성적에대한보고및비교우위의여부는아직근거가부족한실정이다. 향후저위험군에대한치료효과및무증상 CEA고위험군환자에서약물치료와의비교연구결과에따라 CAS의위상이재정립될것으로보인다. 현재까지보고된대표적연구결과를보면, 2004년에발표된 SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) 연구에서 CAS와 CEA의 30일간의이병률및사망률이각각 4.8% 와 9.8% 로나타났고 1년동안의이병률및사망률은각각 12.2% 와 20.1% 로나타나 CAS의우월함을보고하였다. 4) 또한 2005 Coward등이시행한 5개연구의메타분석 (meta-analysis) 에서는양자간의 30일과 1년간의이병률및사망률에큰차이가없음을보고하였다. 13) 반면 2006년에발표된 SPACE (Stent-Supported Percutaneous Angioplasty of the Carotid Artery vs. Endarterectomy) 에서는 CAS와 CEA의 30일간의이병률및사망률이 6.8% 와 6.3% 로의도했던 CAS의비열등성 (non-inferiority) 의입증에실패하였다. 5) 같은년도에발표된 EVA-3S (Endarterectomy vs. Stenting in Patients with Symptomatic Severe Carotid Stenosis) 에서는 CAS 와 CEA 각각 9.6% 와 3.9% 로현저한차이를보여연구가조기종료되기도하였다. 14) 이처럼완료된연구들에서는아직한쪽의우열을판단하기힘들다. 현재 ICSS 15) (International Carotid Stenting Study), CREST 16) (Carotid Revascularization Endarterctomy vs. Stent Trial), ACT-I (Asymptomatic Carotid Stenosis Stenting vs. Endarterectomy Trial), ACST-2 (Second Asymptomatic Carotid Surgery Trial), TACIT (Transatlantic Asymptomatic Carotid Intervention Trial) 등과같은저위험군및무증상환자에대한대규모무작위연구가진행되고있어그결과에귀추가주목되고있다. 결 현재 CAS는 CEA의보완적치료로서뿐만아니라경동맥협착증의일차적치료로자리를잡아가고있으며최근의일부비교연구에서도성적의대등함또는우월함이입증되고있다. 본연구에서도 CAS의성적은기존의여러연구들과비슷한결과를보여안전성을입증하였고 CEA와의비교하여대등한치료임을보여주었다. 하지만아직무증상고위험군및저위험군에서의연구가부족한상태로향후이에대한연구를통해 CAS의유용성이정립될것으로보이며, 경동맥협착증의적합한치료대상및방법의선택이명확해지리라본다. 더불어 CAS는비침습적이라는거대한장점을바탕으로향후장비와기술의발전을통해지속적인치료성적의향상을이루어나아갈것으로예상된다. 론 중심단어 : 경동맥 스텐트 혈관성형술 경동맥내막절제술. REFERENCES 01) North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 325:445-53, 1991 02) Bockenheimer SA, Mathias K. Percutaneous transluminal angioplasty in arteriosclerotic internal carotid artery stenosis. AJNR Am J Neuroradiol 4:791-2, 1983 03) Theron J, Raymond J, Casasco A, Courtheoux F. Percutaneous angioplasty of atherosclerotic and postsurgical stenosis of carotid arteries. AJNR Am J Neuroradiol 8:495-500, 1987 04) Yadav JS, Wholey MH, Kuntz RE, Fayad P, Katzen BT, Mishkel GJ, et al. Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 351:1493-501, 2004 05) Ringleb PA, Allenberg JR, Bruckmann H, Eckstein HH, Fraedrich G, Hartmann M, et al. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet 368:1239-47, 2006 06) Bates ER, Babb CJ, Casey DE, Cates CU, Duckwiler GR, Feldman TE, et al. ACCF/SCAI/SVMB/SIR/ASITN 2007 Clinical Expert Consensus Document on carotid stenting. Vasc Med 12:35-83, 2007 07) Das S, Bendok BR, Getch CC, Awad IA, Batjer HH. Update on current registries and trials of carotid artery angioplasty and stent placement. Neurosurg Focus 18:e2, 2005 08) White CJ, Iyer SS, Hopkins LN, Katzen BT, Russell ME. Carotid Kor J Cerebrovascular Surgery 9(4):271-6, 2007 275

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