ORIGINAL ARTICLE Korean Circ J 2007;37:641-646 Print ISSN 1738-5520 / On-line ISSN 1738-5555 Copyright c 2007 The Korean Society of Cardiology TAXUS TM 스텐트시술후스텐트혈전증발생률과임상경과 전남대학교병원심장센터, 1 전남대학교심혈관계특성화연구사업단, 2 전남대학교의과학연구소 3 문재연 1,2,3 정명호 1,2,3 김인수 1 전충환 1 조정선 1,2 정종원 1,2 심두선 1,2 홍영준 1,2,3 김주한 1,2,3 안영근 1,2,3 조정관 1,2,3 박종춘 1,2,3 강정채 1,2,3 The Frequency, Treatment and Clinical Outcomes of Stent Thrombosis after Use of TAXUS TM Stent Jae-Youn Moon, MD 1,2,3, Myung Ho Jeong, MD 1,2,3, In Soo Kim, MD 1, Chung Hwan Jun, MD 1, Jung Sun Cho, MD 1,2, Jong Won Chung, MD 1,2, Doosun Sim, MD 1,2, Young Joon Hong, MD 1,2,3, Ju Han Kim, MD 1,2,3, Youngkeun Ahn, MD 1,2,3, Jeong Gwan Cho, MD 1,2,3, Jong Chun Park, MD 1,2,3 and Jung Chaee Kang, MD 1,2,3 1 The Heart Center of Chonnam National University Hospital, 2 Cardiovascular Research Institute of Chonnam National University, 3 Chonnam National University, Research Institute of Medical Sciences, Gwangju, Korea ABSTRACT Background and Objectives: Findings from randomized controlled trials have showed that there is no difference in the development of stent thrombosis (ST) in patients implanted with drug-eluting stents (DES) as compared to the use of bare metal stents. The aim of this study was to evaluate the incidence, clinical characteristics, and clinical outcome of ST after implantation of TAXUS TM stents in routine clinical practice. Subjects and Methods: This was a retrospective, single center cohort study. The study included 1,584 patients that underwent successful TAXUS TM stent implantation (2,513 lesions treated) between May 2004 and Dec 2006. Results: ST developed in 18 patients (1.14%) of the 1,584 patients. Acute ST occurred in one patient (0.06%), subacute ST occurred in nine patients (0.57%), and late ST developed in eight patients (0.51%). Sixteen patients that developed ST received medication with dual antiplatelet agents. The incidence of ST in patients with acute coronary syndrome (ACS) showed was higher than in patients with stable coronary disease. The mean follow-up duration for patients was 13.3 months. There were 13 myocardial infarctions and 3 deaths attributable to ST. Conclusion: The cumulative incidence of ST that was confirmed by angiography after successful TAXUS TM stent implantation in consecutive real-world patients was substantially higher than the rate reported in clinical trials. Patients with ACS should be treated more aggressively as the risk of stent thrombosis is higher than for patients with stable angina. A large prospective study for the identification of predictors of DES thrombosis should be conducted. (Korean Circ J 2007;37:641-646) KEY WORDS: Stents; Thrombosis; Angina pectoris; Myocardial infarction. 서 론 약물용출스텐트 (drug-eluting stent, DES) 의일반화된 Received: May 18, 2007 Revision Received: August 1, 2007 Accepted: August 14, 2007 Correspondence: Myung Ho Jeong, MD, The Heart Center of Chonnam National University Hospital, 8 Hak-dong, Dong-gu, Gwangju 501-757, Korea Tel: 82-62-220-6243, Fax: 82-62-228-7174 E-mail: myungho@chollian.net 사용은재협착의빈도를현저하게줄임으로써관상동맥질환환자들에게재협착으로인한반복적인경피적관상동맥중재술을감소시켰을뿐만아니라, 다혈관질환에서도관상동맥우회술을대신하여스텐트의사용을가능하게하였다. 1-7) 대표적으로쓰이는스텐트로는 Sirolumus-eluting stent (Cypher ) 와 Paclitaxel eluting stent (TAXUS TM ) 가있으며, 두종류의스텐트는서로다른약제를사용했으나, 결과적으로스텐트내의내막증식을억제하는기전을통해재협착을감소시켰다. 2)3) 하지만최근들어이러한 DES와관련된스 641
642 TAXUS TM Stent for Thrombosis 텐트혈전증 (stent thrombosis) 에대한보고가증가하고있으며, 스텐트혈전증이발생할경우좋지않은예후를보이는것으로나타났다. 8-10) 하지만, 기존에발표되었던대규모의계획된임상연구들을재분석한연구에서는 DES 가과거에쓰여지던비약물용출형스텐트 (bare metal stent) 에비하여스텐트혈전증의빈도가높지않음을보고하였다. 11-14) 하지만최근에실제임상에서는스텐트혈전증의빈도가대규모의계획된임상연구들보다는높다는보고가있으며, 실제임상에계획된임상연구의결과들을일률적으로적용하는것은옳지않다는주장이제기되었다. 15) 또한기존의연구들에서는스텐트내혈전증은항혈소판제제의조기중단과관련이있는것으로보고되고있어, 실제임상에서는상당수의환자들에게서항혈소판제제를중지하지못하고 1년이상지속적으로사용하고있는상황이다. 16-18) 또한스텐트혈전증이발생한후이에대한치료적인방법및경과에대해서도아직까지정립되지않은상황이다. 19) 따라서본연구는실제임상에서 TAXUS TM 스텐트를시술받은환자들을대상으로혈전증의빈도를알아보고이에대한임상적특징및치료후의경과에대해서알아보고자진행되었다. 대상및방법 대상본연구는단일기관후향적인연구로 2004 년 5월부터 2006 년 12 월까지 29 개월간전남대학교병원심장센터에서 TAXUS TM 스텐트를성공적으로시술받은총 1,584 명 (63.2±19.6 세, 남자 : 1,093 명, 2,511 병변 ) 을대상으로하였다. 방법 스텐트혈전증의정의및연구방법본연구에서스텐트혈전증의정의는갑작스런심근허혈증상과이에동반된심전도상에서의급성허혈변화를보였거나혈액검사상심근효소수치의상승을보인환자중에서관상동맥조영술에서스텐트내의혈전으로인해혈관의부분적혹은완전폐쇄소견을보이는경우로정의하였다. 전체환자중에서스텐트혈전증이발생한빈도를첫번째연구목표로삼았으며스텐트혈전증이발생한환자군의임상적특징및치료후의경과를분석하는것을두번째연구목표로삼았다. 연구의진행은전남대학교병원에서관상동맥조영술및스텐트삽입술을시행받은환자들중 TAXUS TM 스텐트를삽입한환자들만을추출하여분석하였으며, 부가적으로환자들이관상동맥조영술및확장성형술을시행할당시의의무기록을분석하여당시의임상진단및과거력그리고당시의관상동맥조영술의병변특징들을분석하였으며, 환자들의임상경과는외래경과의추적관찰에대한의무기록을확인하였다. 스텐트삽입과약물치료스텐트삽입술은대퇴동맥의천자이후 7Fr sheath 를삽입한후 sheath 를통해유도관을삽입하였으며모든시술은유도관과유도철사를통해진행되었다. 본원에서시행한스텐트삽입술은대부분관상동맥풍선확장술이후에협착이잔존하는경우에스텐트를삽입하였으며, TAXUS TM 스텐트삽입에대한결정은시술자의주관적인판단하에진행되었다. 성공적인스텐트삽입은스텐트삽입후잔존협착이 30% 미만인경우로정의하였다. 스텐트삽입후잔존협착이남아있는경우에는부가적인풍선확장술을시행하여잔존협착이최소가되게끔시술하였다. 연구대상에관상동맥혹은관상동맥 graft 에삽입된스텐트만이포함되었으며, 그외말초혈관이나경동맥의분지에삽입된스텐트는제외하였다. 스텐트삽입술전에모든환자들에서 aspirin 100 mg과 clopidogrel 75 mg의전처치가시행되었으며, 응급실로내원한급성관동맥증후군환자들은 300 mg의 clopidogrel 과 300 mg의 aspirin 의전처치를시행하였다. 약물용출스텐트를삽입한환자들은 aspirin 100 mg의경우평생그리고 clopidogrel 75 mg 은최소 6개월이상복용하는것을원칙으로하였다. 본연구에서는스텐트삽입술후 aspirin 과 clopidogrel 그리고 cilostazol의사용여부에대한기록을조사하였으며, 약물치료를중단한이후에스텐트혈전증이발생한경우에는약물치료를중단하게된이유에대해서도조사하였다. 통계분석모든자료는평균 ± 표준편차로표시하였으며통계분석에는 SPSS (Statistical Package for Social Science, SPSS Inc, Chicago, IL, USA) for windows, version 13.0을사용하였다. 본연구는스텐트혈전증의빈도에대해서조사하였으며스텐트혈전증이발생한빈도를환자의스텐트시술당시의임상진단에따라차이가있는지를 Chi-square test 와 Fisher s exact test 를통해서분석하였다. 본연구에서는 p 값이 0.05 미만일경우통계적으로유의하다고평가하였다. 결 과 관상동맥조영술에서확인된스텐트혈전증의빈도총 1,584 명중 18명 (1.14%) 의환자에서스텐트혈전증이 Table 1. Initial clinical diagnosis in the patients who developed stent thrombosis Clinical diagnosis (n) Number of stent thrombosis (%)* Stable angina (279) 00 (0.00) Unstable angina (634) 08 (1.26) Non-ST elevation myocardial infarction (171) 02 (1.17) ST elevation myocardial infarction (500) 08 (1.60) Total (1,584) 18 (1.14) *p=0.162 by Fisher s exact test
Jae-Youn Moon, et al. 643 관상동맥조영술로확인되었으며, 병변의수로는 0.72% (18/ 2511) 의빈도로발생하였다. 급성스텐트혈전증은 1명 (0.06%) 에서, 아급성스텐트혈전증은 9명 (0.57%) 에서, 후기스텐트혈전증은 8명 (0.51%) 에서발생했다. 환자의임상진단명에따른스텐트혈전증의빈도는 Table 1과같다. 스텐트삽입당시의임상진단에따른스텐트혈전증의빈도는통계학적으로유의하지는않았으나, ST 분절상승의심근경색증을포함한급성관상동맥증후군환자들에서많이발생하는경향을보였다. 대부분의환자들은특별한사유가없으면 aspirin 과 clopidogrel 을중단하지않고유지한것으로나타났다. 또한 cilostazol 의경우는시술직후부터 1개월까지복용하여삼제요법 (aspirin+clopidogrel+cilostazol) 을유지하였으며복잡병변 (complex lesion) 의시술혹은스텐트를여러개시술받은경우가아니면중단하고이후부터이제요법 (aspirin+ clopidogrel) 을유지하였다. 임상적특성스텐트혈전증이발생한환자 18 명의임상적특징은 Table 2 Table 2. Clinical parameters in the patients who developed taxus stent thrombosis No Sex Age Clinical Dx DM HT Smoking Time to ST (day) ST type Treatment Death 01 M 57 STEMI No No Current 001 Acute CABG No 02 M 58 UA No No Current 002 SubA Balloon No 03 M 60 UA No No ex-smoker 002 SubA Balloon No 04 M 59 NSTEMI Yes No Current 004 SubA Balloon No 05 M 69 UA Yes No No 005 SubA Balloon No 06 M 53 UA No No No 005 SubA Balloon No 07 M 51 STEMI No No Current 005 SubA Balloon Yes 08 M 50 UA Yes No ex-smoker 006 SubA Stent No 09 F 84 STEMI No No No 006 SubA Balloon Yes 10 M 63 STEMI Yes No Current 016 SubA Balloon No 11 M 45 NSTEMI No Yes Current 040 Late Suction No 12 M 65 STEMI No Yes Current 070 Late Balloon No 13 M 47 STEMI No No ex-smoker 120 Late Balloon No 14 F 64 STEMI No No No 180 Late Balloon No 15 M 40 STEMI No No Current 230 Late Balloon No 16 M 57 UA No No ex-smoker 235 Late Balloon No 17 M 48 UA No No ex-smoker 630 V-Late Stent No 18 M 67 UA No No ex-smoker 900 V-Late Balloon Yes No Vessel No. Lesion Lesion type Bifurcation CTO ISR lesion Stent diameter (mm) Stent length (mm) Underexpansion* Aspirin Clopidogrel Cilostazol Presentation 01 1-VD p-lad B2 No No No 3.75 32 - + + + STEMI 02 1-VD p-lad C No No No 3.75 32 - + + + STEMI 03 3-VD LM p-lcx B2 Yes No No 3.75 16 - + + + UA 04 3-VD OM B2 No No No 2.75 20 - + + - NSTEMI 05 2-VD p,m-lad C No Yes Yes 3.75 32 + + + + STEMI 06 1-VD p-lcx C No No No 3.75 32 - + + + UA 07 2-VD m-lad B2 No No No 3.75 32 + + + + STEMI 08 3-VD m-rca B1 No No No 2.75 24 + + + + UA 09 3-VD p-rca C No No No 3.75 24 - + + + STEMI 10 3-VD d-rca C No No No 2.57 20 - + + + UA 11 2-VD d-lcx B2 No No No 2.75 24 - + + + NSTEMI 12 2-VD p,m-lad C No No No 3.75 32 - + + - STEMI 13 2-VD m-lad C No No Yes 3.50 32 - + + - STEMI 14 1-VD m-lad C No No No 3.75 20 - + + - STEMI 15 1-VD m-lad B1 No No No 3.50 20 - + + - STEMI 16 3-VD d-lcx B1 No No No 3.75 28 - + + - UA 17 1-VD p-lcx B1 No No No 3.75 32 - + - - NSTEMI 18 1-VD m-rca B2 No No Yes 3.75 32 - - - - STEMI *Stent underexpansion was confirmed by intravascular ultrasound (IVUS) study. DM: diabetes mellitus, HT: hypertension, STEMI: ST segment elevation myocardial infarction, UA: unstable angina, NSTEMI: non ST segment elevation myocardial infarction, SubA: subacute, V-Late: very late, CABG: coronary artery bypass graft, CTO: chronic total occlusion, ISR: instent restenosis, VD: vessel disease, LM: left main, LAD: left anterior descending, LCx: left circumflex artery, OM: obtuse marginal, RCA: right coronary artery, p: proximal, m: middle, d: distal
644 TAXUS TM Stent for Thrombosis 와같다. 환자들은대부분남자들이었으며고혈압이나당뇨병의위험인자들보다는흡연의과거력이많았다. TAXUS TM 스텐트를삽입받았던환자들의대부분이급성관상동맥증후군환자들이었으며, 스텐트혈전증이발생한환자들모두는처음시술당시에급성관상동맥증후군의진단하에시술받은환자들이었다. 스텐트혈전증의임상적발현또한심근경색증으로발현되는경우가 13 명 (72.2%) 이었으며 [ST 분절상승심근경색증 : 10명 (55.6%), ST 분절비상승심근경색증 : 3명 (16.7%)], 나머지환자들은불안정형협심증이었다. 대부분의환자들은심전도의변화를보이거나갑작스런흉통을호소하여응급으로관상동맥조영술을시행하여스텐트혈전증을치료하였다. 스텐트혈전증이발생한환자중 16명에서 (88.9%) aspirin 과 clopidogrel 을복용하고있던중에발생하였다. 또한이중에서는삼제요법이유지되고있었던환자는 10명이었다. 스텐트의불안전팽창 (stent incomplete expansion) 이스텐트혈전증당시에시행한혈관내초음파에서증명된경우가 3명있었으며, 3명모두에서삼제요법을시행하고있는상태에서스텐트혈전증이발생하였다. 스텐트혈전증의치료및경과환자들의치료는풍선확장술만을시행한경우가 14명이었으며풍선확장술이후에스텐트삽입을시행한환자가 2명, suction catheter 로혈전을제거한경우가 1명, 응급관상동맥우회술을시행한환자가 1명있었다. 풍선확장술만한경우이후 6개월추적관상동맥조영술에서 3명의환자에서재협착이나타나 Cypher stent (1명) 및풍선확장술재시행 (2명) 등으로치료하였다. 환자들의평균임상추적관찰기간은 13.3±9.4 개월이었으며, 임상적으로스텐트혈전증을치료받은후퇴원한이후에는다른임상사건없이지내는것으로나타났다. 하지만스텐트혈전증으로치료받고생존한모든환자들은이제요법을유지하고있는상태였다. 스텐트혈전증이발생한환자들중 3명 (16.7%) 이사망하였는데, 사망원인으로는방실전도차단에의한심인성쇼크로사망한경우가 1명, 그리고만성심부전에의한사망이 1명, 악성종양과관련된폐렴으로사망한경우가 1명등이었다. 다른환자들은외래추적관찰에서심부전이나다른유의할만한임상사건이없는상태로약물치료중이다. 고찰 기존에보고되었던대규모의계획된연구들에서의스텐트혈전증의빈도는그리흔하지않을것으로발표되었으며이의빈도는과거에사용되었던비약물용출형스텐트에서나타났던빈도와비슷한것으로발표되었다. 하지만대규모의계획된연구들의결과들을실제임상에적용하는것은문제가있다. 임상연구들에서는대부분어느정도규격에맞는환자들만을골라서진행하게되므로심근경색증등의혈전성폐쇄 (thrombotic occlusion) 로심근괴사가있는불안정한환자상태나응급으로시행되는일차적관상동맥중재술혹은분지부병변 (bifurcation lesion) 이나만성완전폐쇄 (chronic total occlusion) 등복잡병변등은임상연구의대상에서제외된다. 따라서실제임상에서약물용출스텐트의스텐트혈전증의빈도가높지않다고결론내리는것은문제가있을것으로생각되며, 실제임상에서는대규모의계획된임상연구에서발표된스텐트혈전증의빈도보다는현저히많을것으로사료된다. 15) 최근의실제임상연구결과에서는좀더많은빈도로스텐트혈전증이나타남을보고하고있다. 8)20) 최근에발표된외국에서의연구결과를살펴보면 3년간의추적관찰한결과 TAXUS 스텐트혈전증의빈도는 1.7% 까지도보고되고있다. 21) 하지만아직까지 TAXUS 스텐트의실제임상에서스텐트혈전증의빈도는국내에서는보고된바가없는상태로서, 본연구에서는관상동맥조영술에서나타나는스텐트혈전증의빈도를 registry data 를통하여조사하고분석하였다. 본연구에서스텐트혈전증의발생빈도는실제임상에서 1.14% 였으며, 관상동맥조영술로확인을하지못한채사망한경우등스텐트혈전증이의심되는 (probable stent thrombosis) 경우들까지고려한다면실제임상에서의 TAXUS 스텐트혈전증의빈도는기존의보고보다는높을것으로사료된다. 본연구에서나타난주목할만한점은스텐트혈전증이 aspirin 과 clopidogrel 을복용중인상태에서발생한경우가예상보다많았으며이는스텐트혈전증이단순히 aspirin 과 clopidogrel 을유지하는것으로예방할수있는간단한문제가아님을시사한다. 스텐트혈전증의예방을위해서대부분의심장내과의사들은현재약물용출스텐트를삽입한환자들에서 aspirin 과 clopidogrel 의유지요법을최소 6개월이상사용하도록권고하고있으나, 단순히약제의유지만으로스텐트혈전증이완벽히예방될수는없을것으로사료되며좀더적극적인시술과관리가필요할것으로사료된다. 본연구에서특징적인점은주로심근경색증과불안정형협심증의환자에서스텐트혈전증의빈도가높았다. 이는최근의스텐트혈전증의발생이스텐트삽입당시의환자상태가급성관상동맥증후군이었던경우가많다는최근의연구와부합된다. 21) 최근에발표된연구에서는실제스텐트삽입된부위를동맥내시경 (angioscopy) 로검사한결과스텐트삽입술후몇개월이지난후에도혈전이남아있는경우가많음을보고하였으며, 22) 이러한현상은아마도심근경색증환자들에서중재적시술및지속적인약물치료를시행함에도불구하고다시심근허혈이발생하거나재경색이발생하는원인들을설명해줄수있는단서라할수있을것이다. 또한스텐트혈전증도같은맥락으로설명될수있을것이다. 즉심근경색을일으킨파열된죽상반과혈전들은스텐트삽입후에도어느정도지속적으로잔존하게되며이러한혈전등에의해서스텐트혈전증의빈도가높을수있다
Jae-Youn Moon, et al. 645 고예측할수있을것이다. 하지만심근경색증환자등에서스텐트혈전증이잘생기는원인이잔존하는혈전때문에좀더스텐트혈전증에취약한것인지아니면스텐트삽입시술당시의불안정형동맥경화반의파열로인해충분한스텐트의확장이이루어지지못하여서발생하는것인지는좀더많은연구가필요할것으로사료된다. 본연구에서주목할만한두번째결과는스텐트혈전증의치료이후환자의임상상태를추적관찰한결과다. 환자들은대부분스텐트혈전증을풍선확장술및항응고요법만으로치료를시행하였으며, 임상추적관찰상스텐트혈전증이재발하는경우등의임상사고없이일상생활을유지하는것이가능하였다. 다만스텐트혈전증의재발가능성을배제할수없어 aspirin 과 clopidogrel 의병합사용을계속유지하고있었다. 현재본교실에서는낮은재협착을보이고스텐트혈전증이없는보다생체적합적인관상동맥스텐트를동물실험및임상연구를통하여개발하고자노력하고있다. 23-30) 특히급성심근경색증, 당뇨병, 만성심부전증환자등과같이스텐트혈전의발생가능성이높은환자에서효과적이고안전하게사용할수있는스텐트개발을위하여노력하고있으며, 응급수술을요하는환자에서 aspirin 과 clopidogrel 을사용하기힘든경우에도사용할수있는스텐트를개발중이다. 본연구의제한점으로는관상동맥조영술로스텐트내혈전이확인된경우만을스텐트혈전증으로정의하였기때문에기존의연구에서 probable stent thrombosis, 혹은 possible stent thrombosis 등을총체적으로스텐트혈전증으로포함하여규정하는것과는빈도에서차이가있을것으로생각된다. 하지만관상동맥조영술에서발생하는스텐트혈전증의빈도가본연구에서처럼높게나왔다는점으로미루어볼때 probable 또는 possible stent thrombosis 의빈도도결코낮지않을것으로사료된다. 또한본연구는후향적인연구로스텐트혈전증발생의위험인자를정확히규명하기는힘들었으며, 앞으로약물용출스텐트의혈전증에대한대규모전향적인연구가필요할것으로사료된다. 요 약 배경및목적최근들어실제임상에서는스텐트혈전증의빈도가대규모의계획된임상연구들보다는높다는보고가있으며실제임상에계획된임상연구의결과들을일률적으로적용하는것은옳지않다는주장이제기되었다. 본연구는실제임상에서 TAXUS TM 스텐트를삽입받은환자들을대상으로스텐트혈전증의빈도를알아보고이의임상적특징및치료후의경과에대해서알아보고자진행되었다. 방법본연구는단일기관후향적인연구로 2004 년 5월부터 2006 년 12 월까지 29 개월간전남대학교병원심장센터에서 TAXUS TM 스텐트를성공적으로시술받은총 1,584 명 (2,511 병변 ) 을연구대상으로하였다. 결과총 1,584 명중 18명 (1.14%) 의환자에서스텐트혈전증이발생하였으며병변의수로는 0.72% (18/2511) 의빈도로발생하였다. 급성스텐트혈전증은 1명 (0.06%) 에서, 아급성스텐트혈전증은 9명 (0.57%) 에서, 후기스텐트혈전증은 8명 (0.51%) 에서발생하였다. 스텐트혈전증이발생한환자중 16 명 (88.9%) 에서 aspirin 과 clopidogrel 을복용하고있던중에발생하였다. 스텐트혈전증의임상적발현또한심근경색증으로발현되는경우가 13명 (72.2%) 이었으며, 이중 3명이사망하였다. 결론 TAXUS TM 스텐트혈전증의발생빈도는실제임상에서 1.14% 이었으며, 관상동맥조영술로확인을하지못한채사망한경우등스텐트혈전증이의심되는 probable 혹은 possible stent thrombosis 까지고려한다면실제임상에서의 TAXUS TM 스텐트혈전증의빈도는기존의연구결과보다는높을것으로사료된다. 중심단어 : 스텐트 ; 혈전증 ; 협심증 ; 심근경색증. Acknowledgments 본연구는전남대학교심혈관계치료재생특성화연구사업단및아시아심혈관연구재단의연구지원에의하여이루어졌음. REFERENCES 1) Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773-80. 2) Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315-23. 3) Stone GW, Ellis SG, Cox DA, et al. A polymer-based, paclitaxeleluting stent in patients with coronary artery disease. N Engl J Med 2004;350:221-31. 4) Colombo A, Drzewiecki J, Banning A, et al. Randomized study to assess the effectiveness of slow- and moderate-release polymerbased paclitaxel-eluting stents for coronary artery lesions. Circulation 2003;108:788-94. 5) Schampaert E, Cohen EA, Schluter M, et al. The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS). J Am Coll Cardiol 2004;43:1110-5. 6) Schofer J, Schluter M, Gershlick AH, et al. Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS). Lancet 2003;362:1093-9. 7) Park SJ, Kim YH, Lee BK, et al. Sirolimus-eluting stent implantation for unprotected left main coronary artery stenosis: comparison with bare metal stent implantation. J Am Coll Cardiol 2005; 45:351-6. 8) Jeremias A, Sylvia B, Bridges J, et al. Stent thrombosis after successful sirolimus-eluting stent implantation. Circulation 2004;109: 1930-2. 9) Park DW, Park SW. Stent thrombosis in the era of the drug-
646 TAXUS TM Stent for Thrombosis eluting stent. Korean Circ J 2005;35:791-4. 10) Park S, Hong GR, Seo HS, Tahk SJ. Stent thrombosis after successful drug-eluting stent implantation. Korean Circ J 2005;35: 163-71. 11) Daemen J, Garcia-Garcia HM, Kukreja N, et al. The long-term value of sirolimus- and paclitaxel-eluting stents over bare metal stents in patients with diabetes mellitus. Eur Heart J 2007;28: 26-32. 12) Ellis SG, Colombo A, Grube E, et al. Incidence, timing, and correlates of stent thrombosis with the polymeric paclitaxel drug-eluting stent: a TAXUS II, IV, V, and VI meta-analysis of 3,445 patients followed for up to 3 years. J Am Coll Cardiol 2007;49:1043-51. 13) Moreno R, Fernandez C, Hernandez R, et al. Drug-eluting stent thrombosis: results from a pooled analysis including 10 randomized studies. J Am Coll Cardiol 2005;45:954-9. 14) Schampaert E, Moses JW, Schofer J, et al. Sirolimus-eluting stents at two years: a pooled analysis of SIRIUS, E-SIRIUS, and C-SIRIUS with emphasis on late revascularizations and stent thromboses. Am J Cardiol 2006;98:36-41. 15) Farb A, Boam AB. Stent thrombosis redux: the FDA perspective. N Engl J Med 2007;356:984-7. 16) De Luca G, Carbone G, Maione A, Gregorio G. In-stent thrombosis after discontinuation of antiplatelet therapy 2 years after DES implantation: a case report. Int J Cardiol 2007;116:399-400. 17) Artang R, Dieter RS. Analysis of 36 reported cases of late thrombosis in drug-eluting stents placed in coronary arteries. Am J Cardiol 2007;99:1039-43. 18) Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Catheter Cardiovasc Interv 2007;69:334-40. 19) Burzotta F, Romagnoli E, Manzoli A, et al. The Outcome of PCI for stent-thrombosis MultIcentre Study (OPTIMIST): rationale and design of a multicenter registry. Am Heart J 2007;153:377, e1-5. 20) Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drugeluting stents. JAMA 2005;293:2126-30. 21) Daemen J, Wenaweser P, Tsuchida K, et al. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet 2007;369:667-78. 22) Oyabu J, Ueda Y, Ogasawara N, Okada K, Hirayama A, Kodama K. Angioscopic evaluation of neointima coverage: sirolimus drugeluting stent versus bare metal stent. Am Heart J 2006;152: 1168-74. 23) Park HW, Jeong MH, Park OY, et al. The long-term clinical effects of heparin coated coronary stent. Korean Circ J 2002;32: 773-80. 24) Kim W, Jeong MH, Cha KS, et al. The effect of anti-oxidants (carvedilol and probucol) loaded stents in a porcine coronary restenosis model. Circ J 2005;69:101-6. 25) Kim W, Jeong MH, Hong YJ, et al. The long-term clinical results of a platelet glycoprotein IIb/IIIa receptor blocker (Abciximab: ReoPro ) coated stent in patients with acute myocardial infarction. Korean Circ J 2004;34:1063-9. 26) Hong YJ, Jeong MH, Kim W, et al. Effect of abciximab-coated stent on in-stent intimal hyperplasia in human coronary arteries. Am J Cardiol 2004;94:1050-4. 27) Park OY, Jeong MH, Kim JH, et al. The inhibitory effects of a platelet glycoprotein IIb/IIIa receptor blocker-coated stent on neointima formation and inflammatory response in porcine coronary stent restenosis. Korean Circ J 2003;33:439-45. 28) Lim SY, Jeong MH. Is heparin-coated stent effective in patients with acute myocardial infarction? Korean Circ J 2004;34:537-9. 29) Kim W, Jeong MH, Kim KH, et al. The clinical results of a platelet glycoprotein IIb/IIIa receptor blocker (abciximab-reopro)- coated stent in acute myocardial infarction. J Am Coll Cardiol 2006;47:933-8. 30) Lim SY, Bae EH, Jeong MH, et al. The effect of oral administration of alpha lipoic acid and alpha lipoic acid coated stent in porcine in-stent restenosis model. Korean Circ J 2006;36:495-502.