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1 대한내과학회지 : 제 89 권제 4 호 급성심근경색증환자에서 Everolimus-eluting Stent 와 Biolimus-eluting Stent 시술후임상경과 1 전남대학교의과대학전남대학교병원심장센터, 2 보건복지부지정전남대학교병원심장질환특성화연구센터, 3 전남대학교의과대학예방의학교실, 4 전남대학교간호대학간호학과, 5 광주기독간호대학간호학과 박인철 1,2 정명호 1,2 김인수 1,2 이정애 3 최진수 3 박인혜 4 채임순 5 정윤아 1,2 현대용 1,2 정해창 1,2 이기홍 1,2 박근호 1,2 심두선 1,2 김계훈 1,2 홍영준 1,2 박형욱 1,2 김주한 1,2 안영근 1,2 조정관 1,2 박종춘 1,2 Clinical Outcome Comparison of Everolimus- and Biolimus-eluting Stents in Patients with Acute Myocardial Infarction In Cheol Park 1,2, Myung Ho Jeong 1,2, In Soo Kim 1,2, Jung Ae Rhee 3, Jin Su Choi 3, In Hyae Park 4, Leem Soon Chai 5 Yun Ah Jeong 1,2, Dae Yong Hyun 1,2, Hae Chang Jeong 1,2, Ki Hong Lee 1,2, Keun-Ho Park 1,2, Doo Sun Sim 1,2, Kye Hun Kim 1,2 Young Joon Hong 1,2, Hyung Uk Park 1,2, Ju Han Kim 1,2, Young Keun Ahn 1,2, Jeong Gwan Cho 1,2, and Jong Chun Park 1,2 1 The Heart Research Center of Chonnam National University Hospital, Chonnam National University Medical School, Gwangju; 2 The Heart Research Center of Chonnam National University Hospital Designated by Korea Ministry of Health and Welfare, Gwangju; 3 Department of Preventive Medicine, Chonnam National University Medical School, Gwangju; 4 Department of Nursing, Chonnam National University College of Nursing, Gwangju; 5 Department of Nursing, Gwangju Christian College of Nursing, Gwangju, Korea Background/Aims: We compared the efficacy and safety of the second-generation everolimus-eluting stent (EES) and the third generation biolimus-eluting stent (BES) in patients with acute myocardial infarction (AMI). Methods: We analyzed 629 consecutive patients (mean age 65.1 ± 11.2 years, 426 males) with AMI undergoing percutaneous coronary intervention from February 2008 to April They were divided into two groups according to stent type (EES group, n = 426; BES group, n = 203). The primary end-point was 2-year major adverse cardiac events (MACEs), defined as the composite of all-cause death, myocardial infarction, target vessel revascularization, non-target vessel revascularization and target lesion revascularization. The secondary end-point was 2-year target lesion failure (TLF). Results: There were no significant differences in baseline characteristics, except that the patients with EES had a significantly higher prevalence of diabetes mellitus (34.7 vs. 22.7%, p = 0.002) and were older (67.1 ± 11.3 vs. 64 ± 12.9 years, p = 0.039) com- Received: Revised: Accepted: Correspondence to Myung Ho Jeong, M.D., Ph.D. The Heart Research Center of Chonnam National University Hospital, Chonnam National University Medical School, 42 Jebong-ro, Dong-gu, Gwangju 61469, Korea Tel: , Fax: , myungho@chollian.net, mhjeong@chonnam.ac.kr * This study was supported by grant of The Korean Health Technology R&D Project, Ministry of Health & Welfare (HI13C1527), Korea. Copyright c 2015 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 - In Cheol Park, et al. BES vs. EES in AMI - pared with the patients with BES. After propensity score matching, 2-year clinical outcomes showed no differences in composite MACEs or TLF between the two groups. Multivariate Cox regression analysis showed that stent type was not a predictor of 2-year mortality or MACEs. However, older age (hazard ratio [HR] 1.037, 95% confidence interval [CI] , p = 0.001), diabetes mellitus (HR 2.247, 95% CI , p = 0.001) and a left ventricular ejection fraction 45% (HR 3.007, 95% CI , p = 0.001) were independent predictors for 2-year MACEs in patients undergoing EES or BES. Conclusions: Patients with BES had similar clinical 2-year outcomes compared with EES patients with AMI. (Korean J Med 2015;89: ) Keywords: Myocardial infarction; Stents; Prognosis 서론 1970년대관상동맥성형술 (percutaneous transluminal coronary angioplasty) 이소개된이후, 약물에반응하지않는관상동맥질환의치료에관상동맥우회수술 (coronary artery bypass graft surgery, CABG) 외에중재시술도시행하게되었다. 그러나여러연구에서풍선을이용한혈관성형술은시술 6개월이내에 40-50% 의재협착이발생하는등문제점이있었고 [1], 이러한문제점을보완하기위해개발된금속스텐트 (bare metal stent) 는재협착률을 10-20% 로줄일수있었지만아직도높은재협착률을보이고있었다 [2,3]. 이를극복하고자여러약물용출스텐트 (drug-eluting stents, DES) 들이개발되었다. 최초의약물용출스텐트인 Cypher stent R (sirolimus-eluting stent, SES) 가임상에도입된뒤, Taxus stent R (paclitaxel-eluting stent, PES), Endeavor stent R (zotarolimus-eluting stent, ZES), Xience V stent R (everolimus-eluting stent, EES) 등의약물용출스텐트가차례로개발되면서관상동맥질환의치료경향이획기적으로변화되었다. 이러한약물용출스텐트의사용으로시술후재협착은현저히줄어들었지만 [4], 시간이경과함에따라폴리머자체가체내에서일으키는부작용들이부각되기시작하였다. 폴리머가스텐트표면에균일하게도포되지않아서약물농도가달라지는문제점도있고, 스텐트가펴짐에따라폴리머가균열을일으켜벗겨지는경우도있다. 이러한폴리머로인해서만성적인염증반응이일어나기도하고, 그결과내피세포의재생에지장을주어스텐트내에혈전이생기는문제점등이대두되었다 [5-7]. 이러한단점을보완하기위해스텐트삽입후에폴리머가생체내에서분해되면서 biolimus 를용출하는생분해성폴리머약물용출스텐트가개발되어현재사용중이다 [8]. 생분해성폴리머약물용출스텐트에대한안정성및지연성스텐트내협착이기 존의지속성폴리머약물용출스텐트와비교하였을때급성심근경색증환자에있어서어떠한지에대한연구가부족한실정이라이에대한연구를시행하였다. 대상및방법연구대상 2008년 2월부터 2012년 4월까지전남대학교병원심장센터에서급성심근경색증으로스텐트삽입술을시행한환자중생분해성폴리머를함유하는 biolimus-eluting stent (BES, Biomatrix Flex R ) 를삽입받은환자 (I군, 64.9 ± 12.9세, 남 : 여 = 150:53명 ) 와지속성폴리머 (durable polymer) 를함유하는 EES (Xience V R ) 를삽입받은환자 (II군, 67.1 ± 11.3세, 남 : 여 = 310:116명 ) 를대상으로하여후향적으로분석하였다. 연구의일차결과는 24개월간발생한누적주요심혈관계사고 (major adverse cardiac events, MACE) 로하였고, 연구의이차결과는 24개월간발생한표적병변실패율 (target lesion failure: cardiac death + target lesion revascularization + non-fatal myocardial infarction) 로하였다. 연구방법환자들의입원기록지및외래기록지와관상동맥중재술기록및영상을통해조사하였고외래내원이중단된환자는전화방문을시행하였으며, 최종경과가확인된기간까지를관찰기간 ( 평균추적검사기간 : BES 662 ± 204일, EES 662 ± 197일 ) 에포함하였다. 관상동맥중재술은관상동맥직경의 70% 이상협착이있는병변에풍선확장술을먼저시행하였고, 이후표준절차에따라서스텐트가삽입되었다. 혈관시술의성공은시술후잔여협착률이 30% 미만이고 thrombolysis in myocardial infarction 혈류가 3단계이상인경우로정의하

3 - 대한내과학회지 : 제 89 권제 4 호통권제 662 호 였다. 급성심근경색증의정의는 troponin I 또는 creatin kinase-mb 와같은심근효소의상승과더불어허혈의증상, 심전도에서 ST-T분절의변화, 새로발생한좌각차단, 병적인 Q파가발생한경우그리고관상동맥내혈전이확인된경우중한가지이상에해당하는경우로정의하였다 [9]. 연구의일차결과 (primary endpoint) 는스텐트시술후 2년간 의누적주요심혈관계합병증으로평가하였으며누적 MACE 는사망, 비치명적심근경색증의재발, 표적병변 (target lesion) 또는표적혈관 (target vessel) 및비표적혈관 (non target vessel) 에대한관상동맥중재술의재시행과 CABG 중에한가지라도발생한경우로정의하였다. 연구의이차결과는표적병변실패율발생으로평가하였다. Table 1. Comparison of demographic and clinical baseline characteristics before and after propensity score matching Before propensity matching After propensity matching BES (n = 203) EES (n = 426) p value BES (n = 198) EES (n = 198) p value Age, yr 64.9 ± ± ± ± Gender, male % 150 (73.9) 310 (72.8) (73.7) 154 (77.8) SBP, mmhg ± ± ± ± DBP, mmhg 79.8 ± ± ± ± HR, bpm 76.5 ± ± ± ± HTN Hx, % 107 (52.7) 216 (50.7) (52.5) 96 (48.5) DM Hx, % 46 (22.7) 148 (34.7) (23.2) 45 (22.7) Smoking, % 124 (61.1) 253 (59.4) (60.6) 127 (64.1) Dyslipidemia, % 8 (3.9) 22 (5.2) (4.0) 11 (5.6) MI type STEMI, % 88 (43.3) 187 (43.9) 85 (42.9) 97 (49.0) NSTEMI, % 115 (56.7) 239 (56.1) 113 (57.1) 101 (51.0) LVEF, % 56.5 ± ± ± ± LVEF < 45% 25 (13.7) 44 (12.1) (12.4) 18 (10.2) Killip class III, % 21 (10.3) 63 (14.8) (10.6) 21 (10.6) Peak CK-MB, ng/ml 74.7 ± ± ± ± Peak troponin-i, ng/ml 55.7 ± ± ± ± Total cholesterol, mg/ml ± ± ± ± Triglyceride, mg/dl ± ± ± ± HDL cholesterol, mg/dl 39.2 ± ± ± ± LDL cholesterol, mg/dl ± ± ± ± Hs-CRP, mg/l 17.5 ± ± ± ± NT pro BNP, pg/ml 2,413 ± 5,680 2,531 ± 5, ,476 ± 5,757 2,064 ± 4, HbA1c, % 7.0 ± ± ± ± Glucose, mg/dl ± ± ± ± Creatinine 1.0 ± ± ± ± Glycoprotein IIb/IIIa inhibitor, % 28 (13.8) 60 (14.1) (13.6) 31 (15.7) Values are presented as mean ± SD for continuous variables and as numbers (%) for categorical variables. BES, biolimus-eluting stent; DBP, diastolic blood pressure; DM, diabetes mellitus; EES, everolimus-eluting stent; HbA1c, glycosylated hemoglobin; HDL, high-density lipoprotein; HR, heart rate; Hs-CRP, high sensitivity C-reactive protein; HTN, hypertension; Hx, history; LDL, low-density lipoprotein; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NSTEMI, non-st-segment elevation myocardial infarction; NT pro-bnp, N-terminal brain natriuretic peptide; SBP, systolic blood pressure; STEMI, ST-segment elevation myocardial infarction

4 - 박인철외 19 인. 심근경색증환자에서약물용출스텐트비교 - 통계분석방법통계분석은마이크로소프트윈도우용으로나온 SPSS program (version 21.0, SPSS Inc., Chicago, IL, USA) 을이용하였다. 연속형변수는평균 ± 표준편차로나타냈고, 범주형변수는빈도및백분율로나타냈다. 범주형변수의비교는카이제곱검정 (Chi-square test), 연속형변수의비교는 Student t-test 를사용하였다. 두군간의나이, 성별, 고혈압, 당뇨병, 이상지질혈증, 흡연, 치료혈관의위치, 다혈관질환유무, left ventricular ejection fraction < 45%, Killip class III, 스텐트직경, 병변길이를공변량으로 propensity score matching (PSM) 을시행하였다. Caliper width 를 0.2 SD로설정하였고, 이는 99% 의 bias를제거할수있는것으로알려져있다. 또한 2년후 MACE 에영향을미치는예후인자에대해분석하기위하여 Cox 비례위험모형 (proportional hazard model) 을이용하였다. 추적관찰기간동안의 MACE 를비교하기위해 Kaplan-Meier 생존곡선을작성하였고, 양군의차이는 log-rank test 를통해비교하였다. p 값이 0.05보다작을때통계학적으로유의하다고정의하였다. Table 2. Comparison of coronary angiographic and procedural characteristics before and after propensity score matching Before propensity matching After propensity matching BES group (n = 203) EES group (n = 426) p value BES group (n = 198) EES group (n = 198) p value ACC/AHA type of culprit lesion, % B1 12 (5.9) 22 (5.2) (6.1) 12 (6.1) B2 177 (87.2) 370 (87.1) (87.4) 170 (85.9) C 14 (6.9) 33 (7.8) (6.6) 16 (8.1) Location of culprit lesion, % LM 5 (2.5) 33 (7.7) (2.5) 5 (2.5) LAD 120 (59.1) 277 (65.0) (58.6) 127 (64.1) LCX 67 (33.0) 165 (38.7) (33.3) 69 (34.8) RCA 80 (39.4) 173 (40.6) (40.9) 78 (39.4) PreTIMI flow, % (39.9) 177 (41.5) (39.9) 82 (41.4) I 11 (5.4) 14 (3.3) (5.6) 7 (3.5) II 71 (35.0) 135 (31.7) (35.4) 62 (31.3) III 40 (19.7) 100 (23.5) (19.2) 47 (23.7) PostTIMI flow, % (0.0) 2 (0.5) (0.0) 1 (0.5) I 1 (0.5) 0 (0.0) (0.5) 0 (0.0) II 0 (0.0) 3 (0.7) (0.0) 1 (0.5) III 202 (99.5) 421 (98.8) (99.5) 196 (99.0) Multivessel disease, % 78 (38.4) 220 (51.6) (29.3) 67 (33.8) Stent size, mm 20.3 ± ± 7.1 < ± ± Stent diameter, mm 3.2 ± ± ± ± Lesion length, mm 21.4 ± ± 13.0 < ± ± Values are presented as mean ± SD for continuous variables and as numbers (%) for categorical variables. BES, biolimus-eluting stent; EES, everolims-eluting stent; ACC/AHA, American College of Cardiology/American Heart Association; LM, left main; LAD, left anterior descending; LCX, left circumflex; RCA, right coronary artery; TIMI, thrombolysis in myocardial infarction.

5 - The Korean Journal of Medicine: Vol. 89, No. 4, 결과대상자의임상적특성전체환자의평균나이는 66 ± 12.16세였으며성별은 73.1% 로남성의비율이더많은것을확인할수있었다 (Table 1). 성별, 고지혈증, 흡연력, 심박동수는두군간에통계적으로유의한차이를보이지않았으나 I군에비해 II군에서나이가많았고 (I군 64.9 ± 12.9 vs. II군 67.1 ± 11.3; p = 0.039) 당뇨병의빈도가높았다 (I군 22.7% vs. II군 34.7%; p = 0.002). Killip class는 II 군에서 class II인환자가 27.2% 로 I군과비교하여높은경향을보였다. 이러한차이점을 PSM을통해보정한후에는두군간에유의한차이는없었다 (Table 1). 진단의학검사실소견내원시에시행한혈액검사에서 total cholesterol, triglyceride, high density lipoprotein-cholesterol, low density lipoproteincholesterol은양군간의유의한차이를보이지않았고 glucose는 I군에비해 II군에서높았지만 (I군 ± 73.2 vs. II 군 ± 93.6 mg/dl; p = 0.004) PSM를통해보정을하였다. 심초음파를이용한좌심실구혈률도두군간에유의한차이를보이지않았다 (Table 1). 관상동맥조영술및중재술의특징관상동맥조영술및중재술시에시술성공률은전체 99.6% 로대부분의스텐트시술은성공적으로이루어졌으며, 각군간의유의한차이는관찰되지않았다. 하지만 I군에비해 II군에서치료혈관 (culprit vessel) 의위치중좌주간지 (left main) 의빈도 (I군 5 vs. II군 33; p = 0.009) 와다혈관질환 (mutivessel disease) 의빈도가높았다 (I군 78 vs. II군 220; p = 0.002). 또한, I군에비해 II군에서시술한스텐트의직경이컸으며, 병변길이도길었다 (Table 2). 그렇지만 PSM을통해보정한후에는두군간에유의한차이는없었다 (Table 2). 임상적경과관찰대상환자 629명중에서 93명 (14.8%) 에서 2년간 MACE 가발생하였으며, 두군간의 MACE 에대하여교차분석을시행하였을때, 두군간의유의한차이를보이지못하였다 (I군 11.3% vs. II군 16.4%; p = 0.092) (Table 3). MACE 세부항목중총사망률 (all cause death) (I군 6.8% vs. II군 7.0%; p = 0.241), 표적병변재개통술 (target lesion revascularization, TLR) (I군 1.5% vs. II군 2.6%; p = 0.380), 표적혈관재개통술 (target vessel revascularization) (I군 0% vs. II군 6%; p = 0.089), 비표적혈관재개통술 (non-target vessel revascularization) (I군 0.5% vs. II군 0.9%; p < 0.556) 은두군간의유의한차이를관찰할수없었다. 표적병변실패율은전체환자중 31명 (4.9%) 에서발생하였으나두군간의유의한차이를보이지못하였다 (I군 3.4% Table 3. Comparison of the composite of clinical outcomes before and after propensity score matching at 2 years Before propensity matching After propensity matching BES group (n = 203) EES group (n = 426) p value BES group (n = 198) EES group (n = 198) p value MACE 24 (11.8) 71 (16.7) (12.4) 19 (9.6) Death All-cause death 18 (8.9) 38 (8.9) (9.3) 8 (4.0) Cardiac death 4 (2.0) 8 (1.9) (2.1) 1 (0.5) TLR 3 (1.5) 12 (2.8) (1.5) 3 (1.5) Non-TLR TVR 0 (0.0) 6 (1.4) (0.0) 2 (1.0) Non-TVR 1 (0.5) 4 (0.9) (0.5) 1 (0.5) Myocardial infarction 1 (0.5) 5 (1.2) (0.5) 2 (1.0) TLF 7 (3.4) 24 (5.6) (3.5) 6 (3.0) ST (definite or probable) 2 (1.0) 7 (1.6) (1.0) 3 (1.5) Values are presented as numbers (%) for categorical variables. BES, biolimus-eluting stent; EES, everolims-eluting stent; MACE, major adverse cardiac events; TLR, target lesion revascularization; TVR, target vessel revascularization; TLF, target lesion failure; ST, stent thrombosis.

6 - In Cheol Park, et al. BES vs. EES in AMI - vs. II군 5.6%; p = 0.113) (Table 3). 스텐트혈전증은전체환자중 9명 (1.4%) 에서발생하였으며, I군 2예, II군 7예로서유의한차이를보이지않았다 (I군 1.0% vs. II군 1.6%; p = 0.516). Kaplan-Meier법을이용한생존분석결과에서도 I군과 II군사이에유의한차이는없었다 (Fig. 1). MACE 와관련된독립예측인자 단변량분석에서 2년간의 MACE 의예측인자중나이 65세 (hazard ratio [HR] 2.494, 95% confidence interval [CI] , p < 0.001), 좌심실구혈률 (HR 3.644, 95% CI , Figure 1. Kaplan-Meier curve of major adverse cardiovascular event-free survival in patients with acute myocardial infarction who underwent BES and EES implantation. MACE, major adverse cardiac events; HR, hazard ratio; CI, confidence interval; BES, biolimus-eluting stent; EES, everolimus-eluting stent. p = 0.001), 수축기혈압 (HR 0.987, 95% CI , p = 0.001), 당뇨병 (HR 2.661, 95% CI , p < 0.001), 다혈관병변 (HR 1.485, 95% CI , p = 0.057) 을공변량으로하여, 2년간의 MACE 에영향에대하여다변량분석을시행하였다. 그결과나이 65세 (HR 1.037, 95% CI , p = 0.001), 당뇨병 (HR 2.247, 95% CI , p = 0.001), 좌심실구혈률 45% (HR 3.007, 95% CI , p = 0.001) 이 MACE 와관련된예측인자였다 (Table 4). 고찰관상동맥중재술은초기의풍선을이용한관상동맥성형술 (balloon angioplasty) 에서출발하였지만여러연구에서풍선을이용한혈관성형술은 6개월이내에 40-50% 재협착이발생하고, 50-75% 의환자들은흉통이빈번하게발생하거나악화되었고 20-30% 의환자는임상적으로필요한재시술을 1년내에시행받게되는미흡한성적을보였다 [1]. 풍선을이용한성형술의이러한문제점을보완하기위하여개발된일반금속스텐트의사용으로 Serruys 등 [7] 의연구에의하면혈관조영술상재발 (angiographic restenosis) 이 10-20% 로감소하였고, 재시술 (TLR) 도 10-15% 로감소하였다. 또한 bare metal stent (BMS) 는시술후초기에생기는문제들인잔여협착 (residual stenosis), 박리 (dissection) 등을줄였고, 원내우회술 (in hospital CABG), 원내심근경색증 (in hospital myocardial infarction) 도감소시켰다. 이후에이를줄이기위하여일반금속스텐트 (BMS) 에지속적으로항증식약물을폴리머기술을통해입혀서지속적으로방출할수있도록약물용출스텐트 (drug eluting stent, DES) 가개발되면서관상동맥질환의치료패턴을완전히바꾸어놓았다. 대부분의연구들에서 BMS에비하여 DES가장기생존율및심근경색증발생에는차이가없으면서반복적인혈관재 Table 4. Cox regression analysis for independent predictors of major adverse cardiac events Univariate Multivariate HR 95% CI p value HR 95% CI p value Age 65 yr < Diabetes mellitus < Initial LVEF 45% Mutivessel disease SBP HR, hazard ratio; CI, confidence interval; LVEF, left ventricular ejection fraction; SBP, systolic blood pressure

7 - 대한내과학회지 : 제 89 권제 4 호통권제 662 호 개통술을줄이는데우수한것으로알려져있다 [10-12]. Chechi 등 [13] 의저자들은급성심근경색증환자들을대상으로 DES 와 BMS 삽입술이후의임상효과를비교한대규모메타분석에서두군간의표적병변의재협착발생률에차이가없다는보고를하였다. 하지만 Bangalore 등 [14] 은 117,762명을대상으로 meta-analysis 를시행하여 DES인 SES, PES, EES, ZES, ZES-Resolute를 BMS와비교하였고 DES가표적혈관관상동맥중재술의재시행을줄이는데는효과적이나, 안정성을나타내는사망, 심근경색증, 스텐트혈전증은 BMS 와차이가없었다는결과를발표하였고 DES 중에서는 EES가안정성및효용성측면에서가장좋은것으로보고하였다 [14-18]. 그리고 2000년대초반개발되었던 1세대약물용출스텐트에비하여 2000년대중후반개발된 2세대약물용출스텐트의사용이재협착과스텐트혈전증과같은문제점들을해결하고좀더나은임상결과를가져올수있을것으로생각되었고, 1세대와 2세대를직접비교한모든연구는 2세대에서좀더우월하거나비슷하며안전하다는증거가제시되었다 [7,19-22]. 이들 1,2 세대약물용출스텐트들은각기다른종류의스텐트모양과폴리머, 약물들을사용하고있지만, 기본적으로이들은재협착을줄일수있는약물과혼합된폴리머가금속으로된스텐트를둘러싸고있으며일정시간후약물이모두방출되고나서도폴리머와금속으로된스텐트는그대로남아있는공통점을가지고있다. 이에대한면역반응결과내피세포의재생에지장을주어스텐트내에혈전이생기는문제점이대두되었다 [5-7]. 이러한단점을보완하기위해스텐트삽입후에폴리머가생체내에서분해되면서약물을용출하게되고이후몸에자연스럽게흡수되는 Biolimus 를용출하는생분해성폴리머약물용출스텐트가개발되었다 [8,23]. 생체분해성폴리머약물용출스텐트는 poly-lactic acid (PLA) 폴리머를사용하는데, PLA는생분해성봉합사재료나정형외과에서사용하는이식용 implant의재료로 30년이상임상에서사용되어오면서그안정성이입증된재료이다. 그리고스텐트가혈관벽에접촉되는면에만폴리머가도포되어있어약물이혈관벽쪽으로만방출되도록고안되었다 [8,23]. 이로써사용되는폴리머의양을줄일수있고, 향후시술부위에서내피세포가안정적으로빨리회복하는데도움을줌으로써이러한기전으로인하여 DES의단점인스텐트재협착및스텐트혈전증을줄일수있을것으로기대되고있는스텐트이다. 최근연구에서는이러한생분해성폴리머 DES가 BMS뿐 만아니라이전세대의 DES와비교하였을때비열등함을인정한여러연구가있었다 [24-30]. Ahmed 등 [22] 은이전에있었던 ISAR-TEST 3, ISAR-TEST 4, LEADERS 의대규모연구환자데이터를이용하여총 4,062 명의환자에있어서 BES와 SES를 4년동안비교하였으며, 그결과표적병변에대한관상동맥중재술의재시행이 SES 환자에비하여 BES 환자에서통계적으로유의하게감소하는것을확인하였다. 또한심근경색증발생률역시 BES 환자에서더욱낮은것을확인할수있었다 (hazard ratio 0.59, 95% CI , p = 0.031). 또한 Lim 등 [31] 은돼지관상동맥에 BES, ZES, EES를삽입하고 1개월동안조직병리학적특성을관찰한결과 BES가좋다는결과를얻기도하였다. 그리고 Comparison of the Everolimus Eluting stent With the Biolimus A9 Eluting Stent (COMPARE II) [32] 와 NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT) [33] 연구들을보면 COMPARE II 연구에서는관찰기간이 12개월밖에되지않아장기관찰기간이필요하다고하였고 NEXT 연구에서는연구대상환자중일차적관상동맥중재술을받은환자가 5% 미만으로일차적관상동맥중재술을받은환자를대표할수없는실정이었다. 따라서이연구는 EES와 BES의안전성과효용성을평가하기위해일차적관상동맥중재술을받은환자를 2년동안관찰하고비교한것이다. 우선 EES에서나이 (I군 64.9 ± 12.9 vs. II군 67.1 ± 11.3; p = 0.039) 가많았고당뇨병의빈도 (I군 22.7% vs. II군 34.7%; p = 0.002) 가더높았으며 Killip class는 class II 인환자가 27.2% 로 BES와비교하여높은경향을보였다. 그렇지만 2년간의 MACE 는양군간의유의한차이를보이지않았다. 또한표적병변실패율과스텐트혈전증에서도양군간의유의한차이를보이지않았다. 본연구에서생분해성폴리머약물용출스텐트가심근경색증환자에서 MACE 와표적병변실패율, 스텐트혈전증과관련해서는우수함을입증할수는없었다. 그이유에는첫째, BES가생분해성폴리머를포함하고있지만최근대규모 registry를이용한연구에서는 acute myocardial infarction 환자에서 EES가 BES보다우수한것으로알려져있다 [34,35]. 둘째, 본연구는추적관찰기간이 2년으로상대적으로짧았기때문에 EES에비해 BES가우수한지에대해평가하기에는불충분한기간이다 [36]. 그리고본연구에서스텐트혈전증은 2년추적관찰기간동안 7명밖에발생하지않았고, BES와 EES 양군간에발생률의차이는없었다. 하지만이후에발생하는후기지연스

8 - 박인철외 19 인. 심근경색증환자에서약물용출스텐트비교 - 텐트혈전증의발생률에차이가없는지에대해서는연구가더필요하다. 본연구는 629명의환자를대상으로시행한소규모연구로진행되어결과해석에제한점이있으나한계점을줄이고자 PSM을통해서비교하였다. 또한스텐트삽입술시에스텐트선택에전적으로시술자에게맡겨져선택적편견 (selection bias) 에의한오류가존재할수있고, 대부분의환자들이퇴원시항혈소판제제를처방받았고 1년이상복용을지속할것을권고하였으나실제로먹었는지에대한기록은남아있지않으므로실제로약물중단에의한스텐트혈전증발생에대한가능성이있고 EES가시술된시점 (2008년) 과 BES가시술된시점 (2010년) 의차이가존재하며그에따라중재시술의기술의차이가존재할수있는부분을배제하지못하였다. 2008년 2월부터 2012년 4월까지전남대학교병원심장센터에서급성심근경색증으로 BES와 EES를삽입한환자 629명을대상으로비교분석한결과, 생분해성폴리머를사용한 BES 는기존의널리사용되는 EES와비교하여심근경색증환자에게사용하였을때에 2년간의심혈관계합병증및표적병변실패율, 스텐트혈전증발생률에유의한차이를보여주지않았다. 생분해성폴리머스텐트에대해서는 2년이후에발생하는후기지연성스텐트혈전증에대한효용이있는지에대해서도추가적인연구가필요할것으로생각된다. 요약목적 : 약물용출스텐트는관상동맥중재술에서현재가장널리사용되는치료전략이지만여러장점에도불구하고스텐트내재협착 (in stent restenosis) 이큰문제로대두되고있다. 이런스텐트내재협착을일으키는주원인으로약물용출이끝난후남아있는폴리머에의한염증반응이지목되고있다. 이를방지하기위해생분해성폴리머를이용한약물용출스텐트가개발되어현재사용중이나이에대한안정성및지연성스텐트내협착이기존의지속성폴리머약물용출스텐트와비교하였을때급성심근경색환자에있어서어떠한지에대한연구가부족한실정이라이에대한연구를시행하였다. 방법 : 2008년 2월부터 2012년 4월까지전남대학교병원심장센터에서급성심근경색증으로스텐트삽입술을시행한환자중 BES를사용한환자 (I군, 64.9 ± 12.9 남 : 여 = 150:53) 과 EES를사용한환자 (II군, 67.1 ± 11.3, 남 : 여 = 310:116) 를대상으로하여후향적으로분석하였다. 두군간의나이, 성별, 고 혈압, 당뇨병, 이상지질혈증, 흡연, 치료혈관의위치, 다혈관질환유무, 스텐트직경, 그리고병변길이를공변량으로 PSM 을시행하였다. 1차연구종료점은 24개월간누적주요심혈관계합병증으로하였고, 2차연구종료점은 24개월간발생한표적병변실패율로하였다. 결과 : 24개월이경과한시점에서일차종료점의누적주요심혈관계합병증발생률은 BES군에서는 11.8%, EES 군에서는 16.7% 였다 (p = 0.113). 사망, 재발성심근경색증, 표적병변재개통술의빈도등은두군간의유의한차이가없었다. 또한누적스텐트혈전증의발생률도두군간의유의한차이는없었다 (I군 1.0% vs. 1.6%; p = 0.516). PSM 후에도두군간의유의한차이는없었다. 결론 : 생분해성폴리머를사용한 BES는기존의널리사용되는 EES와비교하여심근경색증환자에서일차적관상동맥중재술시에사용한후 2년간의심혈관계합병증및표적병변실패율에서유사한임상경과를보여주었다. 중심단어 : 심근경색증 ; 약물용출스텐트 ; 관상동맥중재술 REFERENCES 1. Casscells W, Engler D, Willerson JT. Mechanisms of restenosis. Tex Heart Inst J 1994;21: Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361: Cutlip DE, Chauhan MS, Baim DS, et al. Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials. J Am Coll Cardiol 2002;40: Le Breton H, Plow EF, Topol EJ. Role of platelets in restenosis after percutaneous coronary revascularization. J Am Coll Cardiol 1996;28: Virmani R, Guagliumi G, Farb A, et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? Circulation 2004; 109: Vaknin-Assa H, Assali A, Ukabi S, Lev EI, Kornowski R. Stent thrombosis following drug-eluting stent implantation. A single-center experience. Cardiovasc Revasc Med 2007; 8: Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009; 360: Grube E, Buellesfeld L. BioMatrix Biolimus A9-eluting

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