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1 원저 Korean Circulation J 2004;34(11): 급성심근경색증환자에서혈소판당단백 IIb/IIIa 수용체차단제 (Abciximab:ReoPro ) 부착관상동맥스텐트의장기임상결과 전남대학교병원심장센터, 전남대학교의과학연구소, 1 전남대학교공과대학응용화학공학부 2 김원 1 정명호 1 홍영준 1 박형욱 1 이민구 1 정선영 1 김인수 1 김계훈 1 윤경호 1 강동구 1 홍서나 1 임상엽 1 이상현 1 이연상 1 김주한 1 안영근 1 조정관 1 박종춘 1 김훈 2 조동련 2 강정채 1 The Long-Term Clinical Results of a Platelet Glycorotein IIb/IIIa Recetor Blocker (Abciximab:ReoPro ) Coated Stent in Patients with Acute Myocardial Infarction Weon Kim, MD 1, Myung Ho Jeong, MD 1, Young Joon Hong, MD 1, Hyung Wook Park, MD 1, Goo Min Lee, MD 1, Seon Young Jeong, RN 1, In Soo Kim, MS 1, Kye Hun Kim, MD 1, Kyung Ho Yoon, MD 1, Dong Ku Kang, MD 1, Seo Na Hong, MD 1, Sang Yu Lim, MD 1, Sang Hyun Lee, MD 1, Yeon Sang Lee, MD 1, Ju Han Kim, MD 1, Young Keun Ahn, MD 1, Jeong Gwan Cho, MD 1, Jong Chun Park, MD 1, Hoon Kim, MS 2, Dong Lyun Cho, PhD 2 and Jung Chaee Kang, MD 1 1 The Heart Center of Chonnam National University Hosital, Chonnam National University Research Institute of Medical Sciences, Gwangju, 2 Chemical Engineering of Chonnam National University, Gwangju, Korea ABSTRACT Background and Objectives:The inhibition of coronary restenosis with an Abciximab (ReoPro )-coated stent has reviously been reorted by us. This study investigated the clinical outcomes of atients with acute myocardial infarction (AMI) treated with ReoPro-coated stents. Subjects and Method:A rosective randomized trial was conducted to comare two tyes of stent for the revascularization in 63 atients [ (ReoPro - coated stent):n=32, 53.7±11.8 years, 27 male, and I (control stent):n=31, 55.4±12.1 years, 27 male] with AMI. The rimary effective end oints were major adverse coronary events (MACE):cardiac death, acute myocardial infarction, target lesion revascularization (TLR), in-stent restenosis and late lumen loss at the 1 year clinical and angiograhic follow-us. Results:Baseline clinical characteristics and diameters of stenosis and the minimal luminal diameters were no different between the two grous. There was one myocardial infarction and revascularization during the hosital stay in grou II. Follow-u coronary angiograms were erformed in 71.9 (23/32) and 77.4% (24/31) of grous I and II, resectively. The diameter of stenosis and late loss were significantly lower in grou I than grou II (19.4±5.1 vs. 34.8±5.9%, =0.013;and 0.39± 0.26 vs. 0.89±0.45 mm;=0.008, resectively). However, the restenosis rates were no different between the two grous (21.7 vs. 37.5%, =0.341). One year clinical follow-us were ossible in 98.4% (62/63), and there were two AMI found in grou II, but none in grou I. The TLR rates and total MACE of grou I were relatively lower comared with grou II [12.9 (4/31) vs. 29.0% (9/31);=0.122 and 12.9 (4/31) vs. 35.5% (11/31), =0.038, resectively]. Conclusion:The ReoPro -coated stent was safe, with no stent thrombosis, and effective in atients with AMI. (Korean Circulation J 2004;34(11): ) KEY WORDS:Platelets;Recetor;Coronary artery disease;coronary restenosis;stents. 논문접수일 :2004 년 6 월 28 일심사완료일 :2004 년 7 월 25 일교신저자 : 정명호, 광주광역시동구학 1 동 8 번지전남대학교병원심장센터, 전남대학교의과학연구소전화 :(062) 전송 :(062) myungho@chollian.net 1063

2 서론 협심증, 심근경색증등의관상동맥질환은최근 10년간급증하고있으며한국성인사망의주요한원인이되고있다. 관상동맥질환의치료방법으로서스텐트 (stent) 시술이관상동맥풍선확장술 (PTCA:ercutaneous transluminal coronary angiolasty) 후발생하는급성혈관합병증을 1% 이하로감소시킴으로써관상동맥중재술의보편적인치료방법으로확립되었다. 1) 그렇지만신생내막형성에의한스텐트재협착은 20~30% 정도로아직까지비교적높아서임상적으로해결해야할중요한문제점으로남아있다. 2) 최근기존의스텐트에 raamycin 등의항증식성약물을도포하여신생내막증식을억제하는약물방출스텐트가좋은결과를보이고있다. 즉, 소혈관, 스텐트재협착병변, 당뇨병환자, 긴병변등에서도기존의일반스텐트보다우수한결과를보이고있다. 3-7) Abciximab (ReoPro ) 은혈소판응집의최종단계를차단하는강력한혈소판응집억제제로서혈전내재병변등의고위험군관상동맥중재술의결과를향상시키고단기및장기간사망률감소등주요심장사건감소에효과적이다. 8-11) 또, 다른종류의혈소판당단백질 IIb/IIIa 수용체차단제와달리혈소판의응집을억제할뿐만아니라혈관내피세포나대식세포의 CD11b/18(macrohage- 1 recetor) 에작용하여염증반응을억제하며, 혈관평활근세포의증식을억제하는효과가있다고알려져있다 ) 본교실에서는돼지관상동맥재협착모델을이용하여 ReoPro 부착스텐트의재협착억제효과를보고한바있으며, 18) 임상연구에서관상동맥병변에도안전하고효과적으로시술될수있음을보고한바있다. 19) 본연구에서는관상동맥중재술을시행받는급성심근경색증환자에서 ReoPro 부착스텐트의장기임상결과와안정성을평가하고자하였다. 대상및방법 본연구는단일센터에서시행된무작위, 전향적인연구로서보건복지부의심의및승인을거쳐전남대학교병원교육연구실윤리위원회의허가를얻었으며, 동의서에서명을한환자를대상으로하였다. 환자는 2001 년 8월부터 2003 년 6월까지전남대학교병원심장센터에 1064 서관상동맥중재술을시술받았던환자 63 예를대상으로하였으며, 관상동맥중재술시 ReoPro 부착스텐트를시술한경우를 Ⅰ군 (32 예 ), 대조스텐트를시술한경우를 Ⅱ군 (31 예 ) 으로하였다. 대상환자는 18세부터 80 세사이의환자로서전형적인흉통발현 24시간이후의심근경색증환자중목표혈관의직경 2.5~4.0 mm, 병변길이 15 mm 이하이며, 70% 이상의유의한협착을동반한환자를대상으로하였다. 좌주간지의협착, 분지부의중재술을필요로하는분지부 (bifurcation) 병변, 이식혈관의협착병변, 좌심실구혈율 35% 이하, 항혈소판제를사용할수없는환자는대상에서제외하였다. 사용되어진 ReoPro 부착스텐트는이전의논문 18)19) 에의한방법과동일하게사용하였다. 병변혈관에대한스텐트시술은확립된방법을이용하였다. 기본적으로풍선도자를이용하여전확장 (re-dilation) 을실시하고, 이후에무작위로스텐트를 10~16 기압으로확장하여삽입하였다. 잔여협착이남아있을때스텐트시술후풍선확장을추가적으로시행하였다. 전체환자에서혈소판당단백 IIb/IIIa 차단제는사용되지않았다. 모든환자는경구용 asirin(100~200 mg) 과 ticloidine(500 mg) 혹은 cloidogrel(75 mg) 을시술전부터복용하였는데, asirin 은지속적으로, ticloidine 과 cloidogrel 은시술후 1개월간복용하였다. Hearin 은 5,000 U를정주하고이후시간당 1,000 U 를지속적으로정주하였으며, 관상동맥중재술시술직전 5,000 U를정주하여 activated clotting time(act) 을 250~300 sec로유지하였다. 저분자량헤파린인 Daltearin 을사용시에는동맥초진입시 2500 U를사용하고관상동맥중재술시 5000~7500 U를더사용하였다. 성공적인관상동맥중재술의정의는사망, 급성심근경색증, 긴급경피적재관류술, 긴급외과적우회술등의합병증없이잔여협착이 20% 미만이며, TIMI(Thrombolysis in Myocardial Infarction) 혈류등급 Ⅲ 이상으로하였다. 출혈성합병증은 Thrombolysis in Myocardial Infarction(TIMI) Study Grou의합병증분류에의거하여, 대출혈과소출혈등으로분류하였다. 대출혈은뇌출혈, 4 g/l 이상의헤모글로빈감소, 3 int 이상의수혈을한경우등으로하였다. 소출혈은 4 g/l 미만의헤모글로빈감소, 3 int 미만의수혈을요하는출혈로하였 Korean Circulation J 2004;34(11):

3 다. 혈소판감소증은 10 만 /ul 이하로하였다. 관상동맥조영술은처음관상동맥중재술시및 6개월전후로시행하였으며, 확립된방법으로시행하였다. 최소혈관내경등의정량적분석은스텐트시술전, 직후, 6개월에각각 Phillis H5000 혹은 BH Allura DCI rogram 을이용하여측정하였으며, 관상동맥중재술에참여하지않은검사자에의하여분석이이루어졌다. 스텐트재협착은관상동맥의내경이 40% 이상협착된경우로정의하였고, 후기직경손실 (late lumen loss) 은스텐트시술직후측정된최소혈관내경에서 6개월추적검사시의최소혈관내경의차이로하였다. 추적관찰은 30일, 6개월, 1년째시행되었고, 각각신체검사및협심통증, 주요심장사건등을평가하였다. 추적관상동맥조영술은되도록 6개월째시행되도록하였다. 연구의관상동맥조영술에서일차종결점은정량적관상동맥조영술의후기직경손실과 6개월추적관찰시직경협착률과재협착의빈도로하였고, 임상적일차종결점은임상추적관찰기간동안의사망, 급성심근경색증, 관상동맥우회술 (CABG:coronary artery byass graft surgery) 이나재관상동맥중재술을시행한경우로하였다. 심근경색증의정의는흉통과심전도에서 ST절의상승및 creatine kinase(ck) 와 CK-MB 가 2배이상증가된경우로정의하였고, 혈전성스텐트폐쇄 (acute or subacute stent thrombosis:ast) 는이전에성공적으로치료되었던목표혈관의완전폐쇄 (TI- MI 혈류등급 0 혹은 I) 및혈류를제한하는혈전의존재 (TIMI I 혹은 Ⅱ) 로정의하였다. 모든결과는평균 ± 표준편차나타내었고, 통계처리는 SPSS for Windows 10.0을이용하였다. 양군사이의불연속변수의비교에는 Chi-square test 를이용하였고, 다중변수비교를위하여 ost hoc 분석을포함한 ANOVA test 를이용하여검정하였다. 연속변수의비교에는 Student s unaired t-test 를이용하였다. 값이 0.05 미만인경우를통계적으로유의하다고간주하였다. 결과 대상환자의임상적특징성별과평균연령은 Ⅰ군남자 27예 (84.4%), 53.7± 11.8세, Ⅱ군남자 27예 (87.1%), 55.4±12.1세이었다. 내원시임상진단명은 ST절상승심근경색증이 Ⅰ군 23예 (71.9%), Ⅱ군 23예 (74.1%) 이었고양군간의차이는없었다. 관상동맥질환의위험인자는고혈압 Ⅰ군 50.0%, Ⅱ군 48.4%, 고지혈증 Ⅰ군 28.1%, Ⅱ군 38.7%, 흡연 Ⅰ군 56.3%, Ⅱ군 64.5% 로차이가없었다. 말초혈관질환, 가족력에서양군간의차이가없었다. 심초음파검사결과 Simson 공식에의한좌심실구혈율은 Ⅰ군 58.7±10.5%, Ⅱ군 57.1±12.1% 이었다. 흉통발현이후관상동맥중재술까지의시간은 Ⅰ 군 30±5 시간, Ⅱ군 31±6 시간으로양군간의차이가없었다. 시술전최고 creatine kinase(ck) 수치는 Ⅰ군 1511±1498 IU/L, Ⅱ군 1648±1402 IU/L, CK- MB는 Ⅰ군 160±139 IU/L, Ⅱ군 CK-MB 는 178± 145 IU/L 이었고, 시술후 CK는 Ⅰ군 1368±1349 IU/ Table 1. Baseline clinical characteristics ReoPro - coated stent I control stent Age (years) 53.7± ± Male (%) 27 (84.4) 27 (87.1) Risk factor (%) Current smoking 18 (56.3) 20 (64.5) Hyertension 16 (50.0) 15 (48.4) Hyercholesterolemia 09 (28.1) 12 (38.7) Diabetes mellitus 06 (18.8) 08 (25.8) Clinical diagnosis (%) Non-ST elevation MI 09 (28.1) 08 (25.8) ST elevation MI 23 (71.9) 23 (74.1) Combined vascular disease (%) Periheral 01 (03.1) 00 (00.0) Hemorrhagic stroke 00 (00.0) 00 (00.0) Family history 03 (09.4) 01 (03.2) Previous coronary 01 (03.1) 00 (00.0) rocedure (%) Previous MI 01 (03.1) 00 (00.0) Pain to balloon time 30±5 31± (hours) Left ventricular function (%) Mean ejection fraction 58.7± ± Pre-intervention eak 1511± ± CK (IU/L) Pre-intervention eak CK-MB (IU/L) 160± ± MI: myocardial infarction, CK: creatine kinase, CK-MB: MB isoenzyme of creatine kinase, ST: stent thrombosis 1065

4 L, Ⅱ군 1388±1351 IU/L, CK-MB 는 Ⅰ군 138±115 IU/L, Ⅱ군 150±121 IU/L 으로양군간의차이는없었다 (Table 1). 정량적관상동맥조영술목표병변혈관의분포는좌전하행지가 Ⅰ군 14병변 (43.8%), Ⅱ군 50병변 (67.7%) 로서가장많았고, 양군간의차이는없었다. ACC/AHA 분류에의한병변의분류는 B1형 (Ⅰ군 27병변, Ⅱ군 25 병변 ) 이가장많았고, B2 형병변은 Ⅰ군 5예 (15.6%), Ⅱ군 5예 (16.1%) 로서차이가없었다. 병변혈관수는양군간의차이가없었다. 시술전 TIMI flow 는 TIMI flow 3 병변이 Ⅰ 군 17병변 (53.1%), Ⅱ군 23병변 (74.2%) 으로가장많았고, TIMI flow 0 병변도 Ⅰ군 2병변 (6.3%), Ⅱ군 3 병변 (9.7%) 이있었다. 관상동맥중재술은스텐트시술전사전풍선확장술이전예에서이루어졌고, 선택되어진풍선도자의크기는양군간의차이가없었다. 스텐트시술시스텐트적응증은계획되거나아최적결과 (subotimal result) 에의한경우가 Ⅰ군 90.6%, Ⅱ군 90.3% 로가장많았다. 스텐트길이는 Ⅰ군 17.1±1.1 mm, Ⅱ군 17.3±4.0 mm로서차이가없었고, 스텐트직경은 Ⅰ군 3.34± 0.34 mm, Ⅱ군 3.22±0.38 mm로서차이가없었다 (Table 2). Table 2. Angiograhic characteristics I Diseased vessels (%) Right coronary artery 13 (40.6) 05 (16.1) Left anterior descending 14 (43.8) 21 (67.7) artery Left circumflex artery 05 (15.6) 06 (16.1) Diseased vessel number (%) One vessel 29 (90.6) 22 (71.0) Two vessel 03 (09.4) 07 (22.6) Three vessel 00 (00.0) 02 (06.5) ACC/AHA classification (%) Tye B1 27 (84.4) 25 (80.6) Tye B2 05 (15.6) 05 (16.1) Tye C (03.2) Pre-PCI TIMI flow (%) TIMI flow 0 02 (06.3) 03 (09.7) TIMI flow 1 01 (03.1) 00 (00.0) TIMI flow 2 12 (37.5) 05 (16.1) TIMI flow 3 17 (53.1) 23 (74.2) Pre-dilation balloon (mm) Balloon length 20.0± ± Balloon size 3.34± ± Stent size (mm) 3.34± ± Stent indication (%) 1.0 Elective and 29 (90.6) 28 (90.3) subotimal results Acute closure and 03 (09.4) 03 (09.7) dissection Stent length (mm) 17.0± ± ACC/AHA: American College of Cardiology/American Heart Association, PCI: ercutaneous coronary intervention, TIMI: thrombolysis in myocardial infarction 중재시술과추적관상동맥조영술관상동맥중재술의성공은양군모두 100% 의성공률을보였다. 중재시술과관련된합병증은없었다. Ⅰ군 23예 (71.9%), Ⅱ군 24예 (77.4%) 에서추적관상동맥조영술이시행되어졌다. 추적관상동맥조영술에서재협착은 Ⅰ군 5예 (21.7%), Ⅱ군 9예 (37.5%) 이었고 (=0.341), 양군간의차이는없었다. 내경협착은 Ⅰ군 19.4±5.1%, Ⅱ군 34.8±5.9%(=0.013), 후기손실은 Ⅰ군 0.39±0.26 mm, Ⅱ군 0.89±0.45 mm로 Ⅰ군에서유의하게적었다 (=0.008)(Table 3). 병원내주요심장사건및임상추적결과입원경과중급성혈전성폐쇄에의한심근경색증이 Ⅱ군에서 1예발생하여응급혈관재개통술을시행하였다. 추적관찰은 Ⅰ군 98.7%, Ⅱ군 100% 에서이루어졌고, 추적기간동안주요심장사건의경우사망은양군에서없었고, 급성심근경색증이 Ⅱ군에서 2예 (6.5%) 있었고, Ⅰ군에서는없었다. 목표혈관재관류술은 Ⅰ군 4 예 (12.9%), Ⅱ군 9예 (29.0%) 로서각각양군간의차 Table 3. Quantitative coronary angiograhic results I Follow-u number (%) 5/23 (71.9) 9/24 (77.4) Restenosis rate (%) 5/23 (21.7) 9/24 (37.5) Follow-u diameter 19.40± ± stenosis (%) Reference diameter (mm) 02.90± ± Lesion length (mm) 15.10± ± Late loss (mm) 00.39± ± Korean Circulation J 2004;34(11):

5 Table 4. In-hosital rimary outcomes after stenting 이는없었다. 그렇지만, 전체주요심장사건은 Ⅰ군 4예 (12.9%), Ⅱ군 11예 (35.5%) 로서 Ⅰ군에서유의하게적었다 (=0.038)(Table 4). 고 혈소판당단백 IIb/IIIa 수용체차단제는혈소판응집의마지막단계를차단하는현재까지알려진가장강력한혈소판응집억제제이다. 급성관상동맥증후군환자에서 ReoPro 투여시중재시술초기 시간동안증가되는염증표지자인 C-reactive rotein, interleukin-6, tumor necrosis factor-α 의증가가감소하였고, 이는 ReoPro 의항염증효과로서중성구나단핵구의표면에존재하는수용체로세포의부착 (adhesion) 과백혈구와혈소판의상호작용및혈관손상에대한염증반응에주요한역할을하는 CD 11b/18(macrohage-1 recetor) 와 ReoPro 가교차반응을함으로서세포와세포외기질의관계를방해하고세포사이의접착력을차단하는기전으로생각되고있다 )20)21) 또한, ReoPro 는저분자량의다른혈소판당단백 IIb/IIIa 수용체차단제와는달리평활근세포, 내피세포, 혈소판등에존재하는 vitronectin 수용체를차단하여급성혈관손상후에평활근세포의이동과증식을억제하는것으로알려져있다 )22) 찰 I Success rate (%) 32 (100) 31 (100) 1.00 Primary end oints (%) Cardiac death 00 (00.0) 00 (00.0) 1.00 Acute myocardial infarction 00 (00.0) 01 (03.2) Emergent revascularization 00 (00.0) 01 (03.2) Emergent byass surgery 00 (00.0) 00 (00.0) 1.00 Clinical follow-u number 31 (96.8) 31 (100) 1.0 Follow-u duration (months) 18.4± ±8.0 Total follow-u MACE 04 (12.9) 11 (35.5) Cardiac death 00 (00.0) 00 (00.0) 1.00 Acute myocardial infarction 00 (00.0) 02 (06.5) TLR 04 (12.9) 09 (29.0) CABG 00 (00.0) 00 (00.0) 1.00 MACE: major adverse cardiac events, TLR: target lesion revascularization, CABG: coronary artery byass graft 본연구는 AMI 환자에서 ReoPro 부착스텐트의효과를보고자한최초의무작위, 전향적인연구이다. Reo- Pro 부착스텐트의심근경색환자의재관류시술과관련된유의한합병증은없었으며, 병원내및 30일내급성혈전성폐쇄, 혈관개통률및심근효소의상승및유의한합병증은대조군과차이를보이지않았다. 심근경색증환자들을대상으로한스텐트시술은기왕의혈전용해제에의한재관류요법에비해우수하지만, 23) 아직도재협착, 경색관련동맥의 reocclusion 등이문제로남아있다. 본연구에포함된환자들이증상발생 24시간이후의환자들이어서일차적재개통술을시행한다른연구와직접비교는하기힘들다. 그렇지만, 본연구의스텐트재협착률 21.7%, 혈관재개술 12.9% 는기존의급성심근경색증환자를대상으로스텐트를시술한 Stent PAMI 연구 24) 의 6개월스텐트재협착률, 혈관재개술결과인 20.3%, 7.7%, 그리고 CADILLAC 연구 25) 의 22.2%, 8.9% 에비하여좋은결과를보여주지는못하였다. 또한, 최근의 sirolimus 방출스텐트의심근경색증환자를대상으로시술한초기결과인 RESE- RACH registry 의보고 26) 와 Lemos 등 27) 의 mm 에달하는후기손실 (late loss), 1.1% 의재관류술그리고, 9.4% 의주요심장사건의결과와비교하면스텐트재협착과혈관재개술의측면에서는다소좋지않은결과라하겠다. 그렇지만, 전체주요심장사건에서는대조군과비교하여유의한결과를보였는데, 이결과의주된요인은통계학적으로유의하지는않지만대조군에비해혈관재개술을줄일수있었다는데있다. Jeremia 등 28) 은 652예의환자, 776개의 sirolimus 부착스텐트의 30 일내급성혈전성폐쇄를조사하였는데단지 1.1% 만을보고하여, sirolimus 등의약물부착스텐트에서도급성, 아급성혈전성폐쇄는임상적으로유의한것은아닌것으로보고되고있다. 비록적은예이지만 1년간의추적관찰기간동안 ReoPro 스텐트를시술하였던전체환자에서급성및아급성혈전성폐쇄에의한심근경색증의발생이없었다는것은 ReoPro 부착으로인하여혈소판응집이효과적으로억제되었으며, 또한그효과가장기간지속된다는것을간접적으로의미할수있겠다. 본연구에서시술후 Cloidogrel 등의사용기간은기존스텐트와동일한 1~2 개월을사용하였으며, 이는 sirolimus, Paclitaxel 등의약물방출스텐트와비교시더적은기간을사용한것이다. ReoPro 의사용과관련 1067

6 된유의한출혈성부작용은관찰되지않았고, PCI 도중혈소판당단백 IIb/IIIa 차단제의사용은없었으며, 기타항혈소판치료면에서도대조군과의차이는없었다. 본연구는흉통발생 24시간후의환자를대상으로하였으므로 ReoPro 부착스텐트의급성심근경색증에대한치료효과를명확히하는데제한점이있다. 또, 단일센터의경험으로서대상환자의수가적어결론을일반화시키는데다소무리가있을수있다. 현재혈전을내재한흉통발생 24시간이내의환자들을대상으로한연구가진행중이다. 결론적으로 ReoPro 부착스텐트는시술관련합병증과유의한부작용없이급성심근경색증환자에서관상동맥중재술에사용될수있었으며, 장기주요심장사건을줄일수있었다. (77.4%) 에서추적관상동맥조영술이시행되어져재협착은 Ⅰ군 5예 (21.7%), Ⅱ군 9예 (37.5%) 이었다 (= 0.341). 내경협착은 Ⅰ군 19.4?.1%, Ⅱ군 34.8±5.9% (=0.013), 후기손실은 Ⅰ군 0.3±0.26, Ⅱ군 0.89± 0.45로 Ⅰ군에서유의하게적었다 (=0.008). 추적관찰은 Ⅰ군 98.7%, Ⅱ군 100% 에서이루어졌고, 추적기간동안급성심근경색증이 Ⅱ군에서 2예 (6.5%) 있었다. 목표혈관재관류술은 Ⅰ군 4예 (12.9%), Ⅱ군 9예 (29.0%) 이었지만, 전체주요심장사건은 Ⅰ군 4예 (12.9%), Ⅱ군 11예 (35.5%) 로서 Ⅰ군에서유의하게적었다 (=0.038). 결론 : ReoPro 부착스텐트는급성심근경색증환자에서유의한부작용없이관상동맥중재술에사용될수있었으며, 장기주요심장사건을감소시킬수있었다. 요 약 중심단어 : 혈소판 ; 수용체 ; 관상동맥질환 ; 관상동맥 ; 스텐트. 배경및목적 : Abciximab(ReoPro ) 은강력한혈소판응집억제제일뿐만아니라혈관내피세포나대식세포의 CD11b/ 18 수용체에작용하여염증반응을억제하며, 혈관평활근세포의증식을억제하는효과가있다. 관상동맥중재술을시행받는급성심근경색증환자에서 ReoPro 부착스텐트의장기임상결과를평가하고자하였다. 방법 : 무작위전향적인연구로급성심근경색증으로내원하여관상동맥중재술을시술받았던환자 63 예 (ReoPro 부착스텐트시술 Ⅰ군 [32 예 ], 대조스텐트시술 Ⅱ군 [31 예 ]) 를대상으로하였다. 정량적관상동맥조영술의후기직경손실과 6개월추적관상동맥조영술시직경협착률과재협착의빈도와 1년간의사망, 급성심근경색증, 관상동맥우회술이나목표혈관재개술을시행한경우를조사하였다. 결과 : 연령, 성별, 진단명, 위험인자, 병변혈관의분포, ACC/ AHA 분류에의한병변의분류, 시술전 TIMI flow, 스텐트길이및스텐트직경은차이가없었다. 관상동맥중재술은양군에서전예에서성공하였으며, 시술과관련된합병증은없었다. 입원경과중급성혈전성폐쇄에의한심근경색증이 Ⅱ군에서 1예발생하여응급혈관재개통술을시행하였다. Ⅰ군 23예 (71.9%), Ⅱ군 24예 1068 본연구는보건복지부보건의료기술연구개발사업연구비 (01-PJ1-PG ) 와 2004 년도전남대학교특별사업우수연구자연구비의지원에의하여이루어졌음. REFERENCES 1) Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P. A comarison of balloon-exandable stent imlantation with balloon angiolasty in atients with coronary heart disease. N Engl J Med 1994;331: ) Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M. A randomized comarison of coronary stent lacement and balloon angiolasty in the treatment of coronary artery disease. N Engl J Med 1994;331: ) Morice MC, Serruy PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnar F, Falotico R. A randomized comarison of a sirolimus-eluting stent with standard stent for coronary revascularization. N Engl J Med 2002;346: ) Moussa I, Leon MB, Baim DS, O Neill WW, Poma JJ, Buchbinder M, Midwall J, Simonton CA, Keim E, Wang P, Kuntz RE, Moses JW. Imact of sirolimus-eluting stents on outcome in diabetic atients: a SIRIUS (SIRolImUS-coated Bx Velocity balloon-exandable stent in the treatment of atients with de novo coronary artery lesions) substudy. Circulation 2004;109: ) Degertekin M, Aramatzis CA, Lemos PA, Saia F, Hoye A, Daemen J, Tanabe K, Lee CH, Hofma SJ, Sianos G, McFadden E, van der Giessen W, Smits PC, de Feyter PJ, van Domburg RT, Serruys PW. Very long sirolimus-eluting stent imlantation for de novo coronary lesions. Am J Cardiol 2004;93: Korean Circulation J 2004;34(11):

7 6) Lemos PA, Hoye A, Goedhart D, Aramatzis CA, Saia F, van der Giessen WJ, McFadden E, Sianos G, Smits PC, Hofma SH, de Feyter PJ, van Domburg RT, Serruys PW. Clinical, angiograhic, and rocedural redictors of angiograhic restenosis after sirolimus-eluting stent imlantation in comlex atients. Circulation 2004;109: ) Schofer J, Schluter M, Gershlick AH, Wijns W, Garcia E, Schamaert E, Breithardt G. Sirolimus-eluting stents for treatment of atients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS). Lancet 2003;362: ) EPIC (Evaluation of 7E3 in Preventing Ischemic Comlications) Investigators. Use of a monoclonal antibody directed against the latelet glycorotein IIb/IIIa recetor in highrisk coronary angiolasty. N Engl J Med 1994;330: ) EPILOG (Evaluation in PTCA to imrove Long-Term outcome GP IIb/IIIa Blockade Study Grou) Investigators. Platelet glycorotein IIb/IIIa recetor blockade and low-dose hearin during ercutaneous coronary revascularization. N Engl J Med 1997;336: ) CAPTURE (C7E3 Fab AntiPlatelet Theray in Unstable Refractory angina) Investigators. Randomized lacebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina. Lancet 1997;349: ) Platelet recetor inhibition in ischemic syndrome management in atients limited by unstable sings and symtoms (PRISM-PLUS) Study Investigators. Inhibition of the latelet glycorotein IIb/IIIa recetor with tirofiban in unstable angina and non-q-wave myocardial infarction. N Engl J Med 1998;338: ) Tam SH, Sassoi PM, Jordan RE, Nakada MT. Abciximab (ReoPro, chimeric 7E3 Fab) demonstrates equivalent affinity and functional blockade of glycorotein IIb/IIIa and alha (v) beta3 integrins. Circulation 1998;98: ) Reverter JC, Beguin S, Kessels H, Kuman R, Hemker HC, Coller BS. Inhibition of latelet-mediated, tissue factorinduced thrombin generation by the mouse/human chimeric 7E3 antobody: otentia imlications for the effect of c7e3 Fab treatment of an acute thrombosis and clinical restenosis. J Clin Invest 1996;98: ) Shaell SB, Toman C, Anderson DC, Taylor AA, Entman ML, Smith CW. Mac-1 (CD11b/CD8) mediates adherencedeendent hydrogen eroxide roduction by human and canine neutrohils. J Immunol 1990;144: ) Simon DI, Xu H, Ortel S, Rogers C, Rao NK. 7E3 monoclonal antibody directed against the latelet glycorotein IIb/IIIa cross-reacts with the leukocyte integrin Mac-1 and blocks adhesion to fibrinogen and ICAM-1. Arterioscler Thromb Vasc Biol 1997;17: ) Mickelson JK, Ali MN, Kleiman NS, Lakkis NM, Chow TW, Hughes BJ, Smith CW. Chimeric 7E3 Fab (ReoPro) decreases detectable CD IIb on neutrohils from atients undergoing coronary angiolasty. J Am Coll Cardiol 1999; 33: ) Lefkovits J, Tool EJ. Platelet glycorotein IIb/IIIa recetor antagonists in coronary artery disease. Eur Heart J 1996; 17: ) Kang KT, Jeong MH, Kim NH, Lee SH, Rhew JY, Park JC, Lee SU, Kim KH, Ahn YK, Cho JG, Park JC, Cho DL, Kang JC. The inhibitory effect of latelet glycorotein IIb/IIIa recetor blocker-coated stent on orcine coronary stent restenosis. Korean J Med 2001;60: ) Kim W, Jeong MH, Hong YJ, Lee SH, Park WS, Kim JH, Kim IS, Choi MJ, Ahn YK, Cho JG, Park JC, Cho DL, Kim H, Kang JC. The long-term clinical inhibitory results of a latelet glycorotein IIb/IIIa recetor blocker (Abciximab: ReoPro)-coated stent in atients with coronary artery disease. Korean J Med 2003;65: ) Lincoff AM, Kereiakes DJ, Mascelli MA, Deckelbaum LI, Barnathan ES, Patel KK, Frederick B, Nakada MT, Tool EJ. Abciximab suresses the rise in levels of circulating inflammatory markers after ercutaneous coronary revascularization. Circulation 2001;104: ) Schwarz M, Nordt T, Bode C, Peter K. The GP IIb/IIIa inhibitor abciximab (c7e3) inhibits the binding of various ligands to the leukocyte integrin Mac-1 (CD11b/CD18, alha (M)beta (2)). Thromb Res 2002;107: ) Willerson JT, Golino P, Eidt J, Cambell WB, Buja LM. Secific latelet mediators and unstable coronary artery lesions. Circulation 1989;80: ) Grines CL, Serruys P, O Neill WW. Fibrinolytic theray: is it a treatment of the ast? Circulation 2003;107: ) Grines CL, Cox DA, Stone GW, Garcia E, Mattos LA, Giambartolomei A, Brodie BR, Madonna O, Eijgelshoven M, Lansky AJ, O Neill WW, Morice MC. Coronary angiolasty with or without stent imlantation for acute myocardial infarction. N Engl J Med 1999;341: ) Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, Stuckey T, Turco M, Carroll JD, Rutherford BD, Lansky AJ. Comarison of angiolasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med 2002;346: ) Saia F, Lemos PA, Lee CH, Aramatzis CA, Hoye A, Degertekin M, Tanabe K, Sianos G, Smits PC, McFadden E, Hofma SH, van der Giessen WJ, de Feyter PJ, van Domburg RT, Serruys PW. Sirolimus-eluting stent imlantation in STelevation acute myocardial infarction: a clinical and angiograhic study. Circulation 2003;108: ) Lemos PA, Saia F, Hofma SH, Daemen J, Ong AT, Aramatzis CA, Hoye A, McFadden E, Sianos G, Smits PC, van der Giessen WJ, de Feyter P, van Domburg RT, Serruys PW. Short- and long-term clinical benefit of sirolimus-eluting stents comared to conventional bare stents for atients with acute myocardial infarction. J Am Coll Cardiol 2004;43: ) Jeremias A, Sylvia B, Bridges J, Kirtane AJ, Bigelow B, Pinto DS, Ho KK, Cohen DJ, Garcia LA, Cutli DE, Carrozza JP Jr. Stent thrombosis after successful sirolimus-eluting stent imlantation Circulation 2004;109:

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Microsoft Word - 순9-5.doc Original ORIGINAL Article ARTICLE Korean Circulation J 2005;35:672-676 ISSN 1738-5520 c 2005, The Korean Society of Circulation 급성 ST 절상승심근경색환자에서일차적스텐트삽입술시행시시로리무스용출성스텐트의효과와안전성 인제대학교의과대학내과학교실, 1 울산대학교의과대학서울아산병원내과학교실,