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1 대한내과학회지 : 제 75 권제 4 호 2008 특집 (Special Review) - Perspectives of DES 약물용출스텐트시대의스텐트혈전증 서울대학교의과대학내과학교실, 서울대학교병원순환기내과, 심혈관센터 박경우 김효수 Stent thrombosis in the DES era Kyung Woo Park, M.D., PhD. and Hyo-Soo Kim, M.D., PhD. Department of Internal Medicine, Seoul National University College of Medicine Cardiovascular Center, Seoul National University Hospital, Seoul, Korea Although drug eluting stents (DES) have mostly replaced bare metal stents (BMS) for the treatment of coronary artery stenosis, concern has been raised regarding the possibility of increased stent thrombosis after DES implantation. Despite the relative low frequency of ST, it is of intense interest to clinicians because of its high morbidity and mortality. There is much controversy regarding many aspects of ST and only recently has there been a unified definition of ST proposed by the Academic Research Consortium. We are in need of much more knowledge and insight into the risk factors and pathophysiology of ST as well as what can be done to overcome ST. However, investigators do agree on a few points based on various clinical trials, registry reports, and meta-analyses: 1) The frequency of ST does not seem to differ between BMS and DES, although DES seems to be slightly more prone to late ST; 2) The incidence of ST is very low but its consequences are potentially fatal; 3) several risk factors may be involved in the development of ST and more studies are required to more accurately elucidate the clinical, angiographic, procedural, and maybe genetic risk factors of ST; 4) improvements in DES design along with better adjunctive drug treatment are required in the future to improve long term safety. (Korean J Med 75: , 2008) Key Words: Drug-eluting stent; Stent thrombosis 배경관상동맥중재술은초기의풍선을이용한관동맥성형술 (balloon angioplasty) 에서출발하였지만금속스텐트 (bare metal stent, BMS) 가개발되면서그영역이넓어졌고비약적으로발전하게되었다. 특히금속스텐트에지속적으로항증식약물을폴리머기술을통해입혀서지속적으로방출할수있도록개발된약물방출스텐트 (drug eluting stent, DES) 가 2000년대부터사용되기시작하면서그사용이폭발적으로늘게되었고, 국내에서도스텐트시술환자의 90% 이상이 DES를시술받고있다. DES 의효과, 즉재협착율을줄이고혈관재개통술의필요성을줄이는효과는여러대규모무 작위연구에서증명되었지만최근 DES 삽입후에스텐트혈전증 (stent thrombosis, ST) 의발생빈도가 BMS에비해높다는주장이제기되면서 DES의안전성에대한우려가확산되고있다. 본종설에서는 DES 삽입후발생할수있는스텐트혈전증의정의, 임상적특징, 병태생리, 위험인자와이의극복방안에대해살펴보도록하겠다. 스텐트혈전증의정의최근까지도연구에따라스텐트혈전증의정의가각각달라서연구결과를통합하거나같이이해하기어려운면이있었다. 일반적으로가장확실한스텐트혈전증의정의은혈전에의한스텐트의폐쇄를직접증명하는것이다 ( 부검

2 - The Korean Journal of Medicine: Vol. 75, No. 4, Table 1. Definition of stent thrombosis proposed by the Academic Research Consortium (ARC) Definite ST Definite stent thrombosis is diagnosed when either angiographic or pathological confirmation present Angiographic confirmation of ST * The presence of a thrombus originating in the stent or in the segment 5mm proximal or distal to the stented region and at least one of the following criteria within a 48-h time window: Acute onset of ischemic symptoms at rest (typical chest pain>20 min) New ischemic ECG changes suggestive of acute ischemia Typical rise and fall in cardiac biomarkers Pathological confirmation of stent thrombosis Evidence of recent thrombus within the stent determined at autopsy Probable ST Clinical definition of probable ST is diagnosed after intracoronary stenting in the following cases Any unexplained death within the first 30 d Regardless of the time after the index procedure, and MI that is related to documented acute ischemia in the of the implanted stent without angiographic confirmation of ST and in the absence of any other obvious cause Possible ST Clinical definition of possible ST is diagnosed with andy unexplained death from 30 d after intracoronary stenting until the end of trial follow-up * The incidental angiographic documentation of stent occlusion in the absence of clinical signs or symptoms (silent occlusion) is (for this purpose) not considered a confirmed stent thrombosis. 의한심근경색, 다른원인에의한급사등을모두포함하게되어스텐트혈전증의심각성을과대평가할소지가있다. 이러한문제들을극복하기위해서양의학술연구컨소시움 (academic research consortium, ARC) 에서는새로운표준화된스텐트혈전증의정의를제안하고있다 1). 이분류에는스텐트혈전증과관련된 2개의중요한기준이근간이되는데첫째는스텐트혈전증을발생한임상사건의원인으로볼수있는확신도에따라 ( 표 1), 그리고둘째는최초의시술로부터사건이발생한시점까지의경과시간을기준 ( 그림 1) 으로분류하였다. Figure 1. Classification of stent thrombosis according to time. 또는혈관조영술을통해 ). 하지만이러한엄격한정의를따를경우실제스텐트혈전증에의해급사하거나, 심근경색이발생되었으나조영술을시행하지않는환자들의스텐트혈전증발생을감안하지않게되어실제문제의심각성을과소평가하게된다. 반면, 임상적으로의심되는스텐트혈전증, 즉시술혈관과관련된심근경색부터원인이명확하지않은급사까지모두스텐트혈전증의범위에포함시키는정의를택할경우, 치명적부정맥에의한사망, 다른병변에 스텐트혈전증의임상특징 1. 스텐트혈전증의빈도약물용출스텐트혈전증의빈도는약 1~2% 내외인것으로알려져있다 2-5). BMS 를주로사용하던시기에는대부분 early ST가문제였고, 일부 late ST들이보고되었으나 BMS 시대에 very late ST는거의안생기거나거의보고가없었던것으로알려져있으나 6, 7), DES 의경우 early, late, very late에모두발생하는것으로보고되고있다. 초기에발생하는 early ST의경우 BMS와 DES간에유의한차이가없고오

3 - Kyung Woo Park, et al: Stent thrombosis in the DES era - 히려 DES의위험도가초기에는조금더낮을것으로생각된다 8). 메타분석에서는 BMS의 early ST 빈도가 0.6% 였던반면, DES 인 Sirolimus eluting stent (SES) 와 Paclitaxel eluting stent (PES) 는각각 0.5% 와 0.5% 였던것으로보고되었고 4, 5), 또다른코호트연구에서는 BMS가 1.2% 였던반면, SES와 PES는 1.0% 로보고되었다. Late ST의경우도 BMS와 DES 사이에큰차이가없는것으로생각된다. BMS 시대에서도 late ST의보고가있었으나 (0~1%) 대다수의의사들이관심을기울이지않아서상당부분무시된측면이있다 7, 9). 최근의메타분석에의하면, DES 와 BMS 사이의 late ST 빈도는비슷한것으로보고되었다 (0.2% vs. 0.3%, 95% CI: 0.35~ 2.84; p=1.00) 10). 문제는 1년이후발생하는 very late ST인데, 물론 BMS를사용한환자에서도 late ST가발생한증례보고들이있기는하나 BMS를삽입할경우 very late ST는매우드문것으로받아드려지고있다. DES 의경우, BMS 에비해 very late ST의위험성은증가하는것으로보고되고있다. SES와 BMS를비교한 4개의 randomized trial과 PES와 BMS 를비교한 5개의 randomized trial 의자료를모아서비교한연구에서 1년까지는 DES와 BMS 사이에비슷한 ST 빈도를보였으나 1년이후 very late ST는 DES에서높았던것으로보고되었다 (0.6% vs. 0% for SES vs. BMS, p=0.03; 0.7% vs. 0.2% for PES vs. BMS, p=0.03) 11, 12). 6,000명이상의자료를분석한또다른메타분석에서도전체적인 ST의빈도는비슷하였으나 very late ST는 DES에서더높았던것으로보고하였다 (0.5% vs. 0% for DES vs. BMS, p=0.02). 요약컨데, 스텐트를삽입한후발생하는스텐트혈전증의빈도는약 1~2% 인데, BMS 와 DES 간에 early ST, late ST 간에는유의한차이가없는것으로생각되나현재까지나온결과들을보면 very late ST의위험성은 DES가 BMS에비해약간높은것으로생각된다. 2. 스텐트혈전증의임상적중요성스텐트혈전증은발생빈도가관상동맥중재시술후 1% 내외로상당히드물게발생하는문제임에도불구하고의학분야에서많은관심을끌고논란의대상이되고있는이유는관상동맥중재시술이후생길수있는다른만성합병증에비해훨씬치명적일수있기때문이다. 대표적만성합병증중하나인재협착은대부분서서히혈관의내경이좁아지기때문에만성안정형협심증으로가장흔히발현하지만스텐트혈전증은관상동맥의급성폐쇄를일으키기때문에그발현양상도상당히심각할수있다. 물론어떤부위에 얼마나많은심근에혈류를공급하는혈관이막히느냐에따라발현양상이다를수있지만, 스텐트혈전증은가장흔히심근경색이나급사로발현하게되고 2, 3, 6), 7% 에서 45% 의높은사망률이외국에서보고된바있다 2, 3, 6, 7, 12-14). 그외에도불안전성협심증, 심부전, 부정맥등상당히치명적이고심각한양상으로발현할가능성이높다. 본연구진이정리한한국인스텐트혈전증레지스트리 (Korean Stent Thrombosis, KOST registry) 에서도대부분의환자들이급사또는심근경색증으로발현하였고, 사망률도 22% 를상회하였다. 3. Very late 스텐트혈전증이더많은 DES 가 BMS 보다위험한가? 스텐트혈전증발생환자의상당수가사망하고대부분의환자에서심근경색이발생하는것으로알려져있기때문에비록초기에 DES의이점이있다하더라도장기적으로 very late stent thrombosis가더증가하기때문에 DES가 BMS에비해장기적으로덜안전할지모른다, 즉사망이나심근경색의발생이증가할지모른다는우려가제기되었다 12, 14). 이러한문제제기는특히 2006년유럽심장학회 (European Society of Cardiology Meeting) 에서스웨덴의 SCAAR 자료를이용하여 DES 삽입군에서 6개월이후에사망이나심근경색이 BMS에비해증가한다고보고된이후논란이정점에이르게되었다 15). 뿐만아니라 Camenzind 등은대표적인 DES 중의하나인 SES에대해발표되었던기존논문들의메타분석을통해 SES를삽입한환자들에서 1년이후의사망률이 BMS 군에비해높다는연구를발표하였다 16). 하지만이들연구에는몇가지중요한오류가있어서해석의주의를요한다. 첫째, SCAAR 자료는무작위연구가아니라등록연구 (registry) 이기때문에 DES 군과 BMS 군사이에많은특성의차이가존재하였다. DES 군에당뇨, 고혈압, 신기능부전등의위험인자가더많았고좌심실기능이더나빴으며이전에관상동맥수술이나경피적관상동맥중재시술을받은환자들의빈도도더높았고치료된혈관숫자도더많았다. 둘째, Camenzind의메타분석에서는실제환자자료를이용하여분석하지않았고발표된논문의수치만을이용하여통계처리를하였기때문에생긴오류가있었다. 이후, 실제환자자료를이용하여분석한내용에서는 DES군과 BMS군사이에사망률 ( 사망률 : PES 6.1% vs. BMS 6.6%; hazard ratio [HR], 0.94; 95% CI, 0.70 to 1.26; SES, 6.0% versus BMS, 5.9%; HR, 1.03; 95% CI, 0.80 to 1.30) 이나심근경색의발생에 ( 심근경색발생률 : PES, 7.0% vs. BMS, 6.3%;

4 - 대한내과학회지 : 제 75 권제 4 호통권제 578 호 Table 2. Risk factors or predictors of stent thrombosis Patient related factor Antiplatelet resistance LV dysfunction Acute coronary syndrome Chronic renal failure Diabetes mellitus Genetic polymorphism Procedure related factor Residual dissection Incomplete stent apposition Incomplete stent expansion Lesion related factor Bifurcation lesion Long lesion Thrombus containing lesion Small vessel Antiplatelet agent related factor Discontinuation of antiplatelet therapy HR, 1.06; 95% CI, 0.81 to 1.39; SES, 9.7% vs. BMS, 10.2%; HR, 0.97; 95% CI, 0.81 to 1.16) 유의한차이가없었다 11, 17). 이와같은결과는 DES에따른 late stent thrombosis와이와수반된심근경색및사망의확률이약간증가된것이 early ST의다소감소, 재혈관개통술의필요성과이에수반된합병증의감소로인해서로상쇄되는면이있는것으로해석되고있다. 요약하면 DES 삽입후스텐트혈전증의위험은 early 및 late stent thrombosis까지는 BMS와비슷하나 1 년이후의 very late ST는 DES가약간더위험하다. 하지만, 이러한 very late ST의발생으로인해 DES 삽입후장기적인사망률및심근경색발생율에는유의한차이가생기지는않는데이는초기의얻는이득효과와더불어재협착과이에따르는합병증이상대적으로 DES군에서적어서그럴것으로생각된다. 스텐트혈전증의병태생리스텐트혈전증은한가지기전또는원인으로설명을할수없다는데에는모두가동의하고있고, 그래서현재정확한원인보다는어떤위험인자를가지고있을때스텐트혈전증이호발하는지에대한연구가활발하다. 원인이무엇이되었던간에어떤상황에서잘발생하는지는조금밝혀져있다. 특히스텐트혈전증이발생한여러환자들의특성을그렇지않은환자들과비교하여밝혀진스텐트혈전증의위 험인자들은다양하게보고되고있다 ( 표 2). 스텐트혈전증에는환자요인외에도스텐트의문제, 스텐트시술과정의문제, 항혈소판제에대한반응, 변변의특성등많은요인들이복합적으로관여하는것으로알려져있다. 정확한원인은모르지만그동안제기된가능성들은다음과같다. 1. 과민성반응과광범위한혈관염증 (Hypersensitivty reaction with extensive vasculitis) 스텐트혈전증발생의한기전으로국소과민반응과이에수반된혈관염의가능성이제기되었다 18, 19). 이러한기전은주로병리학자인 Renu Virmani 등에의해주장되고있는데, 이들은스텐트혈전증이발생한환자들의사후관상동맥조직분석에서혈관내피, 중피, 외피에걸쳐광범위한림프구와호산구의침착을관찰하였다. 그외에도스텐트가삽입된부위에 aneurysmal 확장과 fibrin의침착등이보고하였다. 뿐만아니라미국식약청에보고된 DES 레지스트리에서심각한부작용이발생한사건에서 DES에대한과민반응을의심케하는증상을호소한환자들이있음을확인하였고이들중일부의부검결과에서위와같은유사한광범위한혈관염소견을확인하여스텐트혈전증이 DES에대한과민반응과관계가있을가능성을보고하였다. 2. Delayed healing and dysfunctional endothelialization 또다른가능성으로는치유과정의지연과내피기능장애이다. Very late thrombosis가거의생기지않는 BMS와비교해 DES의차이점이지속적인 fibrin 침착과내피세포가스텐트를덮는재내피화과정 (re-endothelialization) 이지연된다는것이다 20). 특히일본의연구자들은혈관내시경을이용하여 DES와 BMS 삽입후 3에서 6개월사이에직접스텐트표면을혈관안에서관찰하여대부분 (87%) 의 DES의경우거의조직으로덮이지않았으나 BMS의경우모든경우 (100%) 에서조직으로완전하게덮였다는사실을보고하였다 21). 스텐트표면의재내피화지연뿐만아니라, 그기능에도문제가있다는보고들이있다. 스텐트삽입 6개월후에관상동맥의내피기능을약물과운동을이용하여측정하였을때, BMS의경우정상적인혈관이완을보인반면, DES 의경우, 혈관수축현상을보여 DES를삽입한혈관에서내피기능장애와산화질소 availablity의감소를유발할가능성이있음을시사했다 22-24)

5 - 박경우외 1 인 : 약물용출스텐트시대의스텐트혈전증 - 3. Incomplete stent apposition 스텐트삽입후시행된혈관내초음파연구에서는 incomplete stent apposition이스텐트혈전증의원인이될수있다고보고되었다. Very late 스테트혈전증이발생한환자에서 incomplete stent apposition의빈도가대조군에비해흔했고 apposition이안된면적도더컸다 25). 하지만또다른연구에서는 DES를넣은환자에서 BMS를넣은환자에비해 incomplete stent apposition의빈도는더흔하였으나최초시술 1년까지추정하였을때주요한심장사건의증가는없었던것으로보고되어 26, 27) 실제 incomplete stent apposition이스텐트혈전증의증가로이어지는지는논란의여지가있다. 한국인스텐트혈전증환자들의특징 : KoST 레지스트리결과전국의 10개대학병원순환기내과에서참여한 KOST 레지스트리를분석한결과한국인에서의위험인자는다음과같았다. 즉, 124건의스텐트혈전증케이스와비슷한시기에중재시술을받은환자로서스텐트혈전증이발생하지않은 2192명의대조군을대상으로다변량분석을한결과, 1. 젊은나이 2. 흡연자 3. 급성심근경색증환자 4. 혈전이많은병변 5. 분지병변 6. 길고가는스텐트 7. 불충분한확장등이위험인자등이스텐트혈전증발생과연관이있었다. 따라서젊은흡연환자로서급성심근경색증이발생하여스텐트를삽입할경우, 혈전이많은분지병변에길고가는스텐트를삽입하면서충분히확장하지않을경우위험도가상당히증가할것으로생각된다. 다만, 아직까지위험인자나예측인자만으로모든스텐트혈전증을설명하지는못한다. 즉, 비교적안정형협심증을가진환자에서다른스텐트혈전증의환자요인을가지고있지않고장기간 dual 항혈소판제제를복용하고있음에도불구하고 ST가생기는환자들이존재하여, 현재까지알려져있는위험인자가없더라고환자가스텐트혈전증의병태생리에유전적소인이작용할가능성이있다. 현재본연구진들은위에서분석한 KOST registry 환자들중유전자확보가가능한경우, 유전자를대량으로분석하는 gene chip 기술을 이용하여약 50만개의유전자다형성을분석하여현재까지보고된임상적, 기계적요인외에도유전적소인이스텐트혈전증의위험인자로작용하는지연구중이다. 스텐트혈전증의예방을위한제안 1. 모든환자에서중재시술이필요한것은아니다. 최근에발표된 COURAGE trial 에서안정형협심증을가진환자에서최초치료를중재시술군과약물요법군으로무작위배정하였을때, 두군간에사망, 심근경색그리고급성관동맥증후군에의한재입원률에유의한차이가없었다 28). 그러므로, 약을한번도사용해보지않은저위험도의안정형협심증에서는우선약물요법을시도해보는것이필요하다. 2. 무조건 DES 를사용하지말고 BMS 도고려하자. BMS를사용할것인지 DES를사용할것인지를결정하는데있어서는재협착의위험성, 출혈의위험성및수술의가능성, 그리고 Late stent thrombosis의위험성등을고려해야하겠다. 병변및환자의특성중에재협착의위험성이낮아서 BMS를사용해도무방한상황은다음과같다. 가. Native vessel 에 de novo lesion 나. 병변의 reference diameter가 3.5 mm 이상다. Lesion length가짧은경우 (focal lesion) 라. 당뇨가없는경우마. Ostial 병변이아닌경우또한출혈의위험성및수술의가능성에대해서는 DES 시술후요구되고있는장기간의 dual antiplatelet therapy 를유지하기어려운환자들에서도 BMS 시술을고려해볼수있겠다. Active pepetic ulcer disease 가있어서 blood transfusion 이필요한경우, 또 6개월또는 12개월내에 dual antiplatelet therapy를중단해야하는 major operation이예정되어있는경우에특히그러하다. 위에서언급한 stent thrombosis 의 multiple risk factor 를가지고있는경우에도 BMS를고려해볼수있는상황이될수있겠다. 3. 적은수의스텐트로깔끔하게성형술을시행하자. 환자요인외에도병변과시술과관련된스텐트혈전증

6 - The Korean Journal of Medicine: Vol. 75, No. 4, 의위험인자도있으므로이런위험을줄이기위한노력도병행되어야필요가있다. 특히충분한 lumen area 확보와적절한 stent apposition이필요하며분지병변에서여러개의스텐트를이용하여시술하는복잡시술이나여러스텐트를겹쳐서넣은것은꼭필요한경우에만시행되어야할것이다 29-31). 4. 시술후환자관리도중요하다. 시술직후의환자상태가좋지않다든지음식섭취가부실하다든지등등전신상태가좋지않을경우에는교감신경이항진됨과동시에탈수가동반될수있다. 이러한경우혈소판응집능이높아지기에일시적으로혈전증이발생할수있다. 이위기만넘기면향후전혀발생하지않을환자라도결국혈전증의희생자가될수있는것이다. 또한퇴원후에도항혈소판제의복용이제대로이루어지는지확인해야한다. 스텐트혈전증의가장중요한위험인자가항혈소판제의조기중단이다. 문제는의사들이병원에서처방을해줘도실제제대로복용하고있는환자들이생각많큼많지않다는것이다. 한연구에서퇴원후 30일이내에환자가임의로 clopidogrel 복용을중단한비율이 14% 에이르렀다 32). 이런임의중단을할위험성은고령자, 사회경제적지위가낮은사람, 기존에심혈관계질환이있는환자, 그리고퇴원당시적절한퇴원교육또는심장재활교육을받지않는사람에서높았던것으로보고되었다. 특히이렇게임의중단한사람에서사망률이 10배이상높았고, 재입원율도거의 2배에육박하여서이중항혈소판제복용에대한순응도가얼마나중요한지를시사하고있다. 장래의이슈 1. 혈소판억제제요법지속기간이중항혈소판제요법은언제까지유지하는것이좋은가? 이에대한연구는부족한실정이어서실제미국 ACC/AHA의권고사항도대규모연구에근거하지못하였다. BMS의경우스텐트삽입후적어도 1개월이상의이중항혈소판제사용을권고하고있다. DES 의경우, 미국식약청으로부터시판허가를처음받았을때만해도 Cypher의경우 3개월이상 Taxus는 6개월이상의이중항혈소판제치료를권유하였다. 하지만최근에미국에서는 12개월의사용을권하고있고, 유럽에서는 6~12개월을권하고있으나근거는없는실정이다. 실제로 KoST 레지스트리결과를보면혈전증이발생한 환자의 60% 정도가아스피린 / 플라빅스를사용하고있는중에발생하는것을보면, 마냥 2약제를오랫동안사용하는것이해결책은아닐것으로판단된다. 중요한것은순환기내과의사가아닌다른분야의의사들이 DES를삽입한환자를진료할때출혈의위험이조금있다고해서무조건적으로항혈소판제를중단하면안된다는것이다. 2. 차세대 DES design 스텐트혈전증을줄이기위해향후개발되는차세대 DES 의디자인개선도요구되고있다. 스텐트혈전증의원인으로지목된 hypersensitivity reaction이나만성염증과, 치유지연등에 1세대스텐트에사용된 polymer 가지목되었기때문에최근개발되고있는스텐트에는이런폴리머를줄이거나없애거나, 생체분해성폴리머를사용하거나, 혈관내피전구세포를스텐트에서붙잡을수있는 biostent와아예스텐트자체가장기적으로인체내에서분해되는 biodegradable stent 도개발되어일부초기임상결과가보고되고있다 33-36). 3. 위험군판별법개발한명의발생가능성때문에 99명의환자에게장기간 2중혈소판억제제를투여하는것은출혈부작용을고려한다면득보다실이많다. 이에발생가능성이높은환자를가려내는작업이급선무라고여겨진다. 관동맥병변과시술에관한국소적요인못지않게, 유전적, 바이오마커등전신요인이중요할것으로생각되므로이에대한새로운연구결과가기다려진다. 맺음말약물방출스텐트 (DES) 에의한스텐트혈전증 (stent thrombosis) 의위험성이증가될수있다는우려가제기되고있지만, 사망이나심근경색및스텐트혈전증의발생에있어서 BMS와유의한차이는없는것으로판명되었다. 스텐트혈전증중에서도 very late stent thrombosis만 BMS에비해증가하는것으로판단된다. 스텐트혈전증의원인은정확하지않으나몇가지가설이있는실정이고위험인자나예측인자는다양하여여러가지기전이복합적으로작용할가능성을시사한다. 스텐트혈전증을예방하기위해서는우선꼭필요한환자에서만스텐트시술을해야하며상황에따라서는 BMS의삽입을고려해볼수도있다. 또한 clopidogrel의사용기간이 BMS에비해서연장되어야하기때문에환자의순응도도 DES를삽입할때반드시고려되어야하겠다

7 - Kyung Woo Park, et al: Stent thrombosis in the DES era - 국문초록 약물용출스텐트의개발로관상동맥협착증의치료에획기적인변화를가져왔다. 현재 DES가많은상황에서기존의 BMS를대체하고있을뿐만아니라관상동맥중재시술자들은점점더어렵고힘든병변을수술없이중재시술을통해해결하고있는실정이다. 하지만 DES 삽입후스텐트혈전증의위험성이증가한다는보고들과함께안전성에대해우려가있는것도사실이다. 실제스텐트혈전증의빈도가매우낮음에도불구하고한번발생하면대다수에서치명적이라는사실때문에임상가들의주목을받고있다. ST의여러 aspect에대해논란이존재하고있고실제 ST에대한체계적이고통합적인정의도최근에서야 ARC에의해주창되었다. 스텐트혈전증에대한위험인자, 병태생리에대한지식과이해가절대적으로부족한형편이고특히이를극복하기위한방안들에대한연구도필요한실정이다. 이러한논란과더불어지식이부족함에도불구하고 ST에대한몇가지사항들에대해서는전문가들의의견이비슷한것으로생각된다 : 1) ST의전체빈도는 BMS와 DES간에유의한차이가존재하지않지만, DES 의경우 BMS에비해후기 ST의위험성이약간증가한다 ; 2) 전반적으로 ST의발생빈도는매우낮으나그결과는치명적일수있다 ; 3) 여러종류의위험인자가 ST 발생에관여할수있고 ST의임상적, 시술적위험인자뿐만아니라유전적위험인자까지정확히규명하기위해많은연구가필요하다 ; 4) 향후장기안전성을극대화하기위해 DES 디자인의개선과약물치료법의발전이요구된다. 중심단어 : 약물용출스텐트 ; 스텐트혈전증 REFERENCES 1) Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, Van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky AJ, Hamon M, Krucoff MW, Serruys P. Clinical end points in coronary stent trials. Circulation. 115: , ) de la Torre-Hernández JM, Alfonso F, Hernández F, Elizaga J, Sanmartin M, Pinar E, Lozano I, Vazquez JM, Botas J, de Prado AP, Hernández JM, Sanchis J, Nodar JM, Gomez-Jaume A, Larman M, Diarte JA, Rodríguez-Collado J, Rumoroso JR, Lopez-Minguez JR, Mauri J; ESTROFA Study Group. Drug-Eluting Stent Thrombosis. Results From the Multicenter Spanish Registry ESTROFA. J Am Coll Cardiol. 11;51: , ) Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, Morger C, Kukreja N, Juni P, Sianos G, Hellige G, van Domburg RT, Hess OM, Boersma E, Meier B, Windecker S, Serruys PW. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice. Lancet. 369: , ) Bavry AA, Kumbhani DJ, Helton TJ, Bhatt DL. Risk of thrombosis with the use of sirolimus-eluting stents for percutaneous coronary intervention. Am J Cardiol. 95: , ) Bavry AA, Kumbhani DJ, Helton TJ, Bhatt DL. What is the risk of stent thrombosis associated with the use of paclitaxeleluting stents for percutaneous coronary intervention? J Am Coll Cardiol. 45: , ) Cutlip DE, Baim DS, Ho KK, Popma JJ, Lansky AJ, Cohen DJ, Carrozza JP Jr, Chauhan MS, Rodriguez O, Kuntz RE. Stent thrombosis in the modern era. Circulation. 103: , ) Wenaweser P, Rey C, Eberli FR, Togni M, Tuller D, Locher S, Remondino A, Seiler C, Hess OM, Meier B, Windecker S. Stent thrombosis following bare-metal stent implantation. Eur Heart J. 26: , ) Ong AT, Hoye A, Aoki J, van Mieghem CA, Rodriguez Granillo GA, Sonnenschein K, Regar E, McFadden EP, Sianos G, van der Giessen WJ, de Jaegere PP, de Feyter P, van Domburg RT, Serruys PW. Thirty-day incidence and six-month clinical outcome of thrombotic stent occlusion after baremetal, sirolimus, or paclitaxel stent implantation. J Am Coll Cardiol. 45: , ) Wang F, Stouffer GA, Waxman S, Uretsky BF. Late coronary stent thrombosis: early vs. late stent thrombosis in the stent era. Catheter Cardiovasc Interv. 55: , ) Moreno R, Fernandez C, Hernandez R, Alfonso F, Angiolillo DJ, Sabate M, Escaned J, Banuelos C, Fernandez-Ortiz A, Macaya C. Drug-eluting stent thrombosis. J Am Coll Cardiol. 45: , ) Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, Colombo A, Schampaert E, Grube E, Kirtane AJ, Cutlip DE, Fahy M, Pocock SJ, Mehran R, Leon MB. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. ;356: , ) Mauri L, Hsieh WH, Massaro JM, Ho KK, D Agostino R, Cutlip DE. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med. 356: , ) Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, Airoldi F, Chieffo A, Montorfano M, Carlino M, Michev I, Corvaja N, Briguori C, Gerckens U, Grube E, Colombo A. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA

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9 - 박경우외 1 인 : 약물용출스텐트시대의스텐트혈전증 - kinetics on neointimal hyperplasia using a novel paclitaxel eluting stent platform. J Am Coll Cardiol. 46: , ) Grube E, Buellesfeld L. BioMatrix Biolimus A9-eluting coronary stent. Expert Rev Med Devices. 3: , ) Scheller B, Hehrlein C, Bocksch W, Rutsch W, Haghi D, Dietz U, Bohm M, Speck U. Treatment of coronary in-stent restenosis with a paclitaxel coated balloon catheter. N Engl J Med. 355: , ) Aoki J, Serruys PW, van Beusekom H, Ong AT, McFadden EP, Sianos G, van der Giessen WJ, Regar E, de Feyter PJ, Davis HR, Rowland S, Kutryk MJ. Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM Registry. J Am Coll Cardiol. 45: ,

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<30332EC6AFC1FD2DB1E8BCBAC8AF2E687770> 대한내과학회지 : 제 75 권제 4 호 2008 특집 (Special Review) - Perspectives of DES 약물방출스텐트의최근동향 울산대학교의과대학, 서울아산병원심장내과 김성환 홍명기 Current status of drug-eluting stents Sung-Hwan Kim, M.D. and Myeong-Ki Hong, M.D., PhD.