대한내과학회지 : 제 89 권제 2 호 2015 http://dx.doi.org/10.3904/kjm.2015.89.2.192 긴관상동맥병변에대한제1세대및 2세대약물용출스텐트중첩시술후 2년간임상경과의비교 1 전남대학교의과대학전남대학교병원심장센터, 2 전남대학교의과대학예방의학교실 오경수 1,2 정명호 1 이정애 2 최진수 2 이두환 1 김정훈 1 박수환 1 김인수 1 현대용 1 정윤아 1 정해창 1 박근호 1 심두선 1 윤현주 1 김계훈 1 박형욱 1 홍영준 1 안영근 1 조정관 1 박종춘 1 Comparison of Clinical Outcomes after Implantation of First- and Second-Generation Overlapping Drug-Eluting Stents to Treat Diffuse Long Coronary Lesions Kyung Soo Oh 1,2, Myung Ho Jeong 1, Jung Ae Rhee 2, Jin Su Choi 2, Doo Hwan Lee 1, Jeong Hun Kim 1, Soo Hwan Park 1, In Soo Kim 1, Dae Yong Hyun 1, Yun Ah Jeong 1, Hae Chang Jeong 1, Keun-Ho Park 1, Doo Sun Sim 1, Hyun Ju Yoon 1, Kye Hun Kim 1, Hyung Uk Park 1, Young Joon Hong 1, Youngkeun Ahn 1, Jeong Gwan Cho 1, and Jong Chun Park 1 1 The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School; 2 Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea Background/Aims: Despite improved revascularization techniques, the clinical outcomes of patients with diffuse coronary artery lesions after percutaneous coronary intervention are unsatisfactory. However, few studies have compared the efficacy of first- and second-generation drug-eluting stents (DES) in patients with diffuse long coronary artery lesions. Methods: Between January 2006 and July 2012, 364 patients who were treated with DES for long coronary artery stenosis (> 30 mm) were enrolled in this study and assigned to either (first-generation DES, 62.3 ± 10.4 years, 136 males, n = 183) or I (second-generation DES, 64.3 ± 10.7 years, 134 males, n = 181). The incidence of major adverse cardiac events (MACE) was compared between the two groups over 2 years of follow-up, and predictive factors associated with MACE were evaluated through a multivariate analysis. Results: Although several coronary angiographic characteristics were different between the two groups, most demographic and baseline clinical variables were the same. The cumulative incidence of MACE was significantly higher in than in I (25.7 vs. 6.6%; p < 0.001), mainly due to reduced target lesion revascularization (21.9 vs. 2.2%; p < 0.001). According to the results of the multivariate analysis, the use of a paclitaxel-eluting stent (PES) (hazard ratio [HR], 5.168; 95% confidence interval [CI], 2.515-10.617; p < 0.001), decreased left ventricular function ( 45%; HR, 3.586; 95% CI, 1.839-6.990; p < 0.001), and diabetes mellitus (HR, 2.984; 95% CI, 1.605-5.548; p < 0.001) were independent contributors to MACE. Received: 2014. 12. 4 Revised: 2015. 1. 22 Accepted: 2015. 2. 25 Correspondence to Myung Ho Jeong, M.D., Ph.D. The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Korea Tel: +82-62-220-6243, Fax: +82-62-227-3105, E-mail: myungho@chollian.net * 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 - 192 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Kyung Soo Oh, et al. Overlapping DES for diffuse long lesion - Conclusions: For patients with diffuse long coronary artery stenosis, the use of second-generation DES improved the clinical outcome compared with first-generation DES. In addition, the use of a PES, left ventricular dysfunction, and diabetes were predictors of MACE after overlapping stenting. (Korean J Med 2015;89:192-200) Keywords: Drug-eluting stents; Percutaneous coronary intervention 서론관상동맥질환의중재시술에사용하는스텐트 (stent) 는좁아진혈관을확장하고풍선확장술후발생할수있는내막박리를치료할수있어서, 일반적인병변에서는관상동맥우회술을대신하여심장질환을치료할수있다 [1,2]. 관상동맥중재시술에있어서스텐트시술이풍선확장술단독에비하여시술초기및장기성적이좋은것으로알려지면서스텐트시술은급격히확산되었다 [3]. 최근에는일반금속스텐트보다약물용출스텐트가초기합병증을줄이고재협착률을낮춘다는임상연구보고가있다 [4]. 그러나관상동맥중재술에사용되는약물용출스텐트의문제점은스텐트내부로신생내막의증식과혈전증이다. 국내연구에서심근경색증환자에서시술한약물용출스텐트의재협착률은 10% 이내로보고하고있다 [5-7]. 다양한약물용출스텐트는재협착을감소시키는효과적인여러방법중하나로써재협착을획기적으로감소시켰으나아직도재협착과혈전이제한점으로남아있고 [8], 특히긴관상동맥병변에대한스텐트시술은짧은스텐트시술보다재협착률이높다는임상결과가나오고있다. 약물용출스텐트가일반금속스텐트에비해재협착률을현저히감소시킨다는것이확립되어가고있으나, 긴협착부위에 2개이상의약물용출스텐트를중첩시술하였을경우에돼지심장실험에서스텐트중첩부위에심한염증반응과재내피화저하를보고한바있다 [9]. 현재까지긴관상동맥병변에서여러개의스텐트를중첩시킨후장기적임상경과를관찰한연구는많지않으며 [8,10], 특히제1세대및 2세대약물용출스텐트의임상경과를비교한연구는많지않다 [11]. 이연구에서는긴관상동맥병변에세대별약물용출스텐트를중첩시술후임상결과를파악해보고자하였다. 대상및방법 2006년 1월부터 2012년 7월까지전남대학교병원심혈관센터에서긴관상동맥병변에약물용출스텐트를중첩시켜시 술받은 2년간임상적추적관찰을시행한환자 364명을대상으로하였다. 이중 1세대약물용출스텐트를 I군 (n = 183, 62.3 ± 10.4, 남 = 136예 ), 2세대약물용출스텐트를 II군 (n = 181, 64.3 ± 10.7, 남 = 134예 ) 으로분류하여후향적분석을진행하였다. 1세대약물용출스텐트는 paclitaxel eluting-stent (PES; Taxus stent, Pico elite stent, Coroflex please stent ) 와 sirolimus eluting-stent (SES; Cypher stent ) 를사용하였고, 2세대약물용출스텐트는 zotarolimus eluting-stent (ZES; Endeavor stent, Resolute integrity stent ) 와 everolimus eluting-stent (EES; Xience stent, Promus stent ) 를사용하였다. 단, 연령이 80세이상고령인환자는제외하였다. 진단명으로는 ST-분절상승심근경색증 (ST elevation myocardial infarction, STEMI), 비ST- 분절상승심근경색증 (non-st elevation myocardial infarction, NSTEMI), 오래된심근경색증 (old myocardial infarction, OMI), 불안정형협심증 (unstable angina pectoris, UAP), 안정형협심증 (stable angina pectoris, SAP) 으로분류하였다. 위험요인으로는흡연, 당뇨병, 고혈압, 고지혈증등을조사하였다. 또한혈류정도를나타내는 Thrombolysis In Myocardial Infarction (TIMI) flow [12] 0, 1, 2, 3, 좌심실구혈률 (left ventricular ejection fraction, LVEF) [13,14], 혈관내경의정량적분석을알수있는관상동맥조영술영상분석 (quantitative coronary angiography analysis, QCA), 병변의복잡도 (American College of Cardiology/ American Heart Association lesion type, [ACC/AHA]) 를조사하였다. 정량적관상동맥조영술 QCA는 2명이상의숙련된검사자가시행하였다. 니트로글리세린을관상동맥내로투여한후시술전, 후추적관상동맥조영술시촬영한혈관조영촬영에대하여 QCA 분석시스템 (Centricity Cardiology CA1000 V2.0, GE Medical systems, Eindhoven, Netherlands) 을사용하여유도도자를기준으로보정하여, 참조혈관직경 (reference diameter, mm) 및표적병변의내경협착 (diameter stenosis, %) 과최소혈관직경 (minimal lumen diameter, mm) 등을측정하였다. - 193 -
- 대한내과학회지 : 제 89 권제 2 호통권제 660 호 2015 - 임상경과추적관찰임상경과는환자들의외래기록지및입원기록지와관상동맥중재술기록및영상을근거로평가하였고외래내원이중단된환자는전화방문을시행하였으며, 최종경과가확인된기간까지를관찰기간에포함하였다. 추적관상동맥조영술은시술후 1년을전후 ( 평균추적검사기간 : 306 ± 212일 ) 하여시행하였고, 허혈증상이있는경우에는임상경과관찰중에즉시시행하였다. 추적관상동맥조영술이되지않은경우에는 2년이내주요심장사건및사망을분석하였다. 긴관상동맥병변은 30 mm 이상혈관을대상으로비교하였고, 추적관상동맥조영술상의재협착 (restenosis) 은정량적관상동맥조영술상스텐트내부나근위부와원위부의각각 5 mm 이내분절의혈관내경이참조혈관직경에비해 50% 이상좁아진경우로정의하였다. 단, 연령이 80세이상고령인환자는제외하였다. 재협착의형태에따라 I형 (IA-ID), II형, III 형, IV형으로분류하였다 [15]. 재협착이있으면서협심증증상이있거나부하검사상심근허혈이증명된경우시술자가판단한방법에의해재개통술을시행하였다. 입원기간및추적기간동안의주요심장사건 (major adverse cardiac events, MACE) 의발생을평가하였고, MACE 는심인성사망, 표적병변과관련된심근경색또는표적병변재개통술 (target lesion revascularization, TLR) 로정의하였다. 통계분석통계분석을위하여 SPSS for Windows 20.0 (Statistical Package for the Social Sciences, SPSS INC., Chicago, IL, USA) 을이용하였다. 연속형자료는평균값 ± 표준편차의형식으로표시하였고, 비연속형자료는빈도및비율 (%) 로기술하였다. 대상비교는 independent t-test, Chi-square test 를시행하였고, 2년후 MACE 에영향을미치는예후인자에대해분석하기위하여단변량분석 (univariate analysis) 과다변량분석 (multivariate analysis) 을시행하였다. 통계적유의수준은 p < 0.05로하였다. 결과환자들의임상적특성입원당시환자의진단명으로 STEMI는 I군 34명 (18.6%), II군 30명 (16.6%), UAP 는 I군 64명 (35.0%), II군 72명 (39.8%), OMI는 I군 5명 (2.7%), II군 5명 (2.8%) 으로서양군간에차이가없었다. SAP 는 I군 43명 (23.5%), II군 19명 (10.5%), NSTEMI Table 1. Baseline clinical characteristics I (n = 181) Age, yr 62.3 ± 10.4 64.3 ± 10.7 0.068 Male, % 136 (74.3) 134 (74.0) 0.951 Clinical diagnosis, % 0.009 Unstable angina 64 (35.0) 72 (39.8) 0.343 Stable angina 43 (23.5) 19 (10.5) < 0.001 STEMI 34 (18.6) 30 (16.6) 0.615 NSTEMI 37 (20.2) 55 (30.4) 0.026 OMI 5 (2.7) 5 (2.8) 0.986 Risk factor, % Smoking 67 (36.6) 65 (35.9) 0.889 Diabetes mellitus 61 (33.3) 72 (39.8) 0.202 Hypertension 89 (48.6) 100 (55.2) 0.207 Dyslipidemia 29 (15.8) 19 (10.5) 0.131 Echocardiographic findings LVEF, % 60.5 ± 11.5 59.1 ± 12.0 0.254 Discharge medication, % Aspirin 168 (97.7) 77 (97.5) 0.921 Clopidogrel 159 (92.4) 69 (87.3) 0.193 Statin 158 (91.9) 71 (89.9) 0.605 ACEI/ARB 132 (76.7) 60 (75.9) 0.890 ß-blocker 141 (82.0) 70 (88.6) 0.183 Values are presented as mean ± SD unless otherwise indicated. STEMI, ST-segment elevation myocardial infarction; NSTEMI, non ST-segment elevation myocardial infarction; OMI, old myocardial infarction; LVEF, left ventricular ejection fraction; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blockers. 는 I군 37명 (20.2%), II군 55명 (30.4%) 은 II군에서많았다 (p = 0.026). 남성 (74.3% vs. 74.0%) 은양군간에차이가없었다 (p = 0.951). 동맥경화증의위험인자인고혈압 (48.6% vs. 55.2%), 당뇨병 (33.3% vs. 39.8%), 흡연 (36.6% vs. 35.9%), 고지혈증 (15.8% vs. 10.5%) 은양군간에차이가없었다. 좌심실구혈률 (LVEF) 은양군간에차이가없었다 (60.5 ± 11.5 vs. 59.1 ± 12.0%, p = 0.254). 퇴원시복용약에서 aspirin (97.7% vs. 97.5%), clopidogrel (92.4% vs. 87.3%), statin (91.9% vs. 89.9%), angiotensin converting enzyme inhibitor or angiotensin receptor blockers (76.7% vs. 75.9%), ß-blocker (82.0% vs. 88.6%) 는양군간에유의한차이가없었다 (Table 1). - 194 -
- 오경수외 19 인. 긴관상동맥병변에약물용출스텐트 - 관상동맥조영술특성 관상동맥중재술을시행한혈관은좌전하행지 (66.1% vs. 53.0%, p = 0.015), 좌회선지 (7.1% vs. 7.7%, p = 0.818), 우관상동맥 (26.8% vs. 39.2%, p = 0.012) 중 I군에서 II군보다좌전하행지, 우관상동맥병변에대한시술이많았다. 시술전 TIMI flow는 TIMI 0 (23.0% vs. 33.1%, p = 0.030), TIMI I (5.0% vs. 4.4%), TIMI II (26.8% vs. 29.8%), TIMI III (45.4% vs. 32.6%, p = 0.013) 는 I군과 II군사이에서 TIMI I, III의경우차이가있었다. ACC/AHA lesion type 은 type B1 (6.0% vs. 3.9%), Type B2 (35.5% vs. 69.6%, p < 0.001), Type C (58.5% vs. 26.5%, p < 0.001) 중 I군에서 type B2 이상의복잡병변이많았다. 만성완전폐쇄병변 (9.3% vs. 13.8%) 은차이가없었다 (p = 0.177). 병변혈관의수는단일혈관병변 (44.8% vs. 43.6%), 두혈관병변 (31.1% vs. 41.4% p = 0.041), 세혈관병변 (24.0% vs. 14.9%, p = 0.028) 중 I군에서두혈관병변이상에서차이가있었다 (Table 2). Table 2. Coronary angiographic findings I (n = 181) Pre-procedure TIMI flow, % 0.076 0 42 (23.0) 60 (33.1) 0.030 1 9 (5.0) 8 (4.4) 0.786 2 49 (26.8) 54 (29.8) 0.517 3 83 (45.4) 59 (32.6) 0.013 Target vessel, % 0.031 LAD 121 (66.1) 96 (53.0) 0.015 LCX 13 (7.1) 14 (7.7) 0.818 RCA 49 (26.8) 71 (39.2) 0.012 ACC/AHA type, % < 0.001 B1 11 (6.0) 7 (3.9) 0.346 B2 65 (35.5) 126 (69.6) < 0.001 C 107 (58.5) 48 (26.5) < 0.001 CTO, % 17 (9.3) 25 (13.8) 0.177 Extent of coronary artery 0.834 disease, % One-vessel 82 (44.8) 79 (43.6) 0.823 Two-vessel 57 (31.1) 75 (41.4) 0.041 Three-vessel 44 (24.0) 27 (14.9) 0.028 TIMI, thrombolysis In myocardial infarction; LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; ACC/AHA, American College of Cardiology/American Heart Association classification; CTO, chronic total occlusion. 관상동맥중재술전후의특성 관상동맥조영술시행후정량적관상동맥조영분석에서 stent 근위부참조혈관내경 (3.1 ± 0.39 mm vs. 3.1 ± 0.50 mm), 병변최소내경 (0.5 ± 0.39 mm vs. 0.4 ± 0.36 mm), stent 원위부참조혈관내경 (2.4 ± 1.00 mm vs. 2.2 ± 1.15 mm), 내경협착 (81.9% vs. 82.0%), 병변길이 (47.3 ± 12.59 mm vs. 46.2 ± 9.65 mm) 는양군간에통계적으로유의한차이는없었다. Stent 평균내경은 II군에서작았다 (3.1 ± 0.26 mm vs. 3.0 ± 0.28 mm, p = 0.023). Stent 평균길이 (57.4 ± 13.30 mm vs. 59.5 ± 12.88 mm, p = 0.124) 는통계적으로유의한차이는없었다. 후기스텐트내손실 (0.32 ± 0.02 mm vs. 0.41 ± 0.04 mm, p = 0.806), 후기분절내강손실 (0.27 ± 0.02 mm vs. 0.24 ± 0.02 mm, p = 0.061) 로분석이되었다. Stent 약물용출성분유형중 SES (18.0%), PES (81.9%), ZES (52.4%), EES (47.5%) 로분석이되었다 (Table 3). 추적관상동맥조영술소견 추적관상동맥조영술은 251 예에서 306 ± 212 일째에시행 Table 3. Procedural findings I (n = 181) QCA Proximal RD, mm 3.1 ± 0.39 3.1 ± 0.50 0.849 MLD, mm 0.5 ± 0.39 0.4 ± 0.36 0.175 Distal RD, mm 2.4 ± 1.00 2.2 ± 1.15 0.246 DS, % 81.9 82.0 0.959 Lesion length, mm 47.3 ± 12.59 46.2 ± 9.65 0.467 Stent Diameter, mm 3.1 ± 0.26 3.0 ± 0.28 0.023 Length, mm 57.4 ± 13.30 59.5 ± 12.88 0.124 In-stent late loss, mm 0.32 ± 0.02 0.41 ± 0.04 0.806 In-segment late loss, mm 0.27 ± 0.02 0.24 ± 0.02 0.061 Stent type, % - SES 33 (18.0) - PES 150 (81.9) - ZES - 95 (52.4) EES - 86 (47.5) Values are presented as mean ± SD unless otherwise indicated. QCA, quantitative coronary angiographic analysis; RD, reference diameter; MLD, minimal lumen diameter; DS, diameter stenosis; SES, sirolimus-eluting stent; PES, paclitaxel-eluting stent; ZES, zotarolimus-eluting stent; EES, everolimus-eluting stent. - 195 -
- The Korean Journal of Medicine: Vol. 89, No. 2, 2015 - Table 4. Follow-up coronary angiographic findings I (n = 68) ISR, % 45 (26.2) 7 (8.9) 0.002 ISR type, % Focal 0.010 IA 1 (2.2) 0 (0.0) 0.497 IB 7 (15.5) 1 (14.2) 0.240 IC 11 (24.4) 2 (28.5) 0.200 ID 1 (2.2) 0 (0.0) 0.497 Diffuse 0.001 II 17 (37.7) 3 (42.8) 0.098 III 3 (6.6) 1 (14.2) 0.779 IV 5 (11.1) 0 (0.0) 0.126 Restenosis location, % Proximal edge 8 (4.7) 2 (2.5) 0.425 Proximal body 11 (6.4) 1 (1.3) 0.077 Overlapping site 23 (13.4) 4 (5.1) 0.048 Distal body 10 (5.8) 1 (1.3) 0.102 Distal edge 4 (2.3) 0 (0.0) 0.172 ISR, in-stent restenosis. 되었고, 스텐트내재협착 (26.2% vs. 8.9%, p = 0.002) 은 I군에서 II군보다많았다. 시술후스텐트내재협착유형 [16] 은 Focal IA (2.2% vs. 0.0%, p = 0.497), IB (15.5% vs. 14.2%, p = 0.240), IC (24.4% vs. 28.5%, p = 0.200), ID (2.2% vs. 0.0%, p = 0.497) 로서양군간에유의한차이는없었다. Diffuse II (37.7% vs. 42.8%, p = 0.098), III (6.6% vs. 14.2%, p = 0.779), IV (11.1% vs. 0.0%, p = 0.126) 형은양군간에유의한차이는없었다. 스텐트내재협착부위로나누었을때근위부스텐트가장자리 (4.7% vs. 2.5%), 근위부스텐트중앙부분 (6.4% vs. 1.3%), 원위부스텐트중앙부분 (5.8% vs. 1.3%), 원위부스텐트가장자리 (2.3% vs. 0.0%) 는통계적으로유의한차이는없었다. 그러나스텐트중첩부분 (13.4% vs. 5.1%, p = 0.048) 의재협착발생률은 I군에서 II군보다많았다 (Table 4). 주요심장사건 병원내사망 (1.6% vs. 0.6%, p = 0.320), 추적관찰기간중심장사로인한사망 (1.6% vs. 2.2%, p = 0.692), 심장과관련없는사망 (1.1% vs. 1.7%, p = 0.644), 후기스텐트혈전증 (0.5% vs. 0.6%, p = 0.994) 은양군간에차이가없었다. 6개월간관찰된 MACE 는양군간에차이가없었다 (5.5% vs. 1.7%, p = Table 5. Clinical outcomes I (n = 181) In-hospital death, % 3 (1.6) 1 (0.6) 0.320 Six-month clinical outcome, % MACE 10 (5.5) 3 (1.7) 0.050 One-year clinical outcome, % MACE 40 (21.9) 11 (6.1) < 0.001 Two-year clinical outcomes, % MACE 47 (25.7) 12 (6.6) < 0.001 MI 3 (1.6) 5 (2.8) 0.465 TLR 40 (21.9) 4 (2.2) < 0.001 Ischemia-driven TLR 18 (10.5) 4 (2.2) 0.160 CABG 1 (0.5) 0 (0.0) 0.319 Cardiac death 3 (1.6) 4 (2.2) 0.692 Non-cardiac death 2 (1.1) 3 (1.7) 0.644 Stent thrombosis 1 (0.5) 1 (0.6) 0.994 MACE, major adverse cardiac event; MI, myocardial infarction; TLR, target lesion revascularization; CABG, coronary artery bypass graft. 0.050). 1년간관찰된 MACE 는 I군에서 II군보다높았고 (21.9% vs. 6.1%, p < 0.001), 2년간관찰된 MACE 는 I군에서 II군보다높았으며 (25.7% vs. 6.6%, p < 0.001), TLR (21.9% vs. 2.2%, p < 0.001) 은 I군에서높았지만, 심근경색증 (1.6% vs. 2.8%, p = 0.465), 관상동맥우회술 (0.5% vs. 0.0%, p = 0.319) 등은양군간에차이가없었다 (Table 5). 주요심장사건에영향을미치는인자 긴관상동맥병변에약물용출스텐트중첩시술후 2년추적관찰에서주요심장사건및사망에미치는예측인자를파악하기위하여단변량분석 (univariate analysis) 에서 paclitaxeleluting stent (hazard ratios [HR], 3.140; 95% confidence interval [CI], 1.787-5.517; p < 0.001), LVEF 45% (HR, 2.904; 95% CI, 1.586-5.317; p < 0.001), 당뇨병 (HR, 1.977; 95% CI, 1.185-3.299; p = 0.009) 이유의한예측인자로분석이되었다. 3개의유의한예측인자를대상으로다변량분석 (multivariate analysis) 을한결과 paclitaxel-eluting stent (HR, 5.168; 95% CI, 2.515-10.617; p < 0.001), 45% 이하의좌심실구혈률 (HR, 3.586; 95% CI, 1.839-6.990; p < 0.001), 당뇨병 (HR, 2.984; 95% CI, 1.605-5.548; p < 0.001) 이통계적으로유의한예측인자로분석이되었다 (Table 6). - 196 -
- Kyung Soo Oh, et al. Overlapping DES for diffuse long lesion - Table 6. Univariate and multivariate regression analyses for variables predictive of major adverse cardiac events Univariate Multivariate HR 95% CI HR 95% CI Paclitaxel-eluting stent 3.140 1.787-5.517 < 0.001 5.168 2.515-10.617 < 0.001 LVEF 45% 2.904 1.586-5.317 < 0.001 3.586 1.839-6.990 < 0.001 Diabetes mellitus 1.977 1.185-3.299 0.009 2.984 1.605-5.548 < 0.001 ACC/AHA type C 1.524 0.911-2.549 0.108 - - - Multi-vessel disease 1.303 0.769-2.208 0.326 - - - Dyslipidemia 0.707 0.304-1.644 0.420 - - - HR, hazard ratio; CI, confidence interval; LVEF, left ventricular ejection fraction; ACC/AHA, American College of Cardiology/American Heart Association. 고찰이연구에서긴관상동맥병변에서약물용출스텐트시술결과, 제1세대약물용출스텐트시술과비교하여 2세대약물용출스텐트가낮은주요심장사건발생률및재협착률, 재관류술을보여주었다. 관상동맥중재술분야는계속하여발전을거듭하고있고일반금속스텐트를넘어약물용출스텐트가개발된후관상동맥질환치료에많은발전이있었다. 하지만여전히관상동맥우회술보다혈관재개통술의위험성이크고, 약물용출스텐트의장기간추적관찰에대한연구경험이축적되고있지만, 후기스텐트혈전증과스텐트내재협착은아직도중요한문제점으로생각된다. 이에처음개발되었던 1세대약물용출스텐트에비해현재도많이사용되고있는 2세대약물용출스텐트의사용이이러한문제들을해결하고좀더나은임상결과를가져올수있을것으로생각되었다. 세대를비교한각각의연구 [17-20] 에서는 2세대에서양호한결과를보여주거나비슷하다는증거가제시되었고본연구의결과와비슷하였다. 최근에다양한약물용출스텐트를사용하게되면서각각의약물용출스텐트가실제임상에서어떤결과를보이는지에대한연구들이발표되고있다 [21-26]. 이연구에서긴관상동맥병변에약물용출스텐트중첩시술후 2년간임상적추적관찰결과, 주요심장사건및사망에미치는예측인자를다변량분석을통해분석한결과, PES, 저하된좌심실구혈률및당뇨병이통계적으로유의한예측인자이었다. 또한이연구에서는병변의길이가긴관상동맥병변에대하여 2개이상의약물용출스텐트를중첩시술하여스텐트전체길이의합계가 30 mm 이상이었던환자군을대상으로추적관찰한결과 20.7% 의재협착률, 10% 의 MACE 발생률을보였다. 기존에보고된약물용출스텐트사용에대한연구들과비슷 한것으로서 [27-29], 긴관상동맥병변에대하여중첩시술스텐트는비교적효과적인치료방법이라는것을확인할수있었다. 다만제2세대약물용출스텐트중첩시술보다제1세대약물용출스텐트중첩시술에서재협착률이다소높은이유중의하나는제2세대약물용출스텐트중첩시술의추적관상동맥조영술이낮았기때문에두군간에차이가있을것으로생각된다. 단선행연구 [12] 에서주요심장사건및사망에미치는유일한예측인자로분석되었던 ACC/AHA lesion type C는본연구에서통계적으로유의한차이는없었다. 이는전체시술환자 364명중추적관상동맥조영술을받은환자가 251명 (55%) 으로서, 비교적낮은추적관상동맥조영술이하나의요인으로생각된다. 기본임상특징으로관상동맥질환의위험인자로잘알려진당뇨병은선행연구에서차이가있었지만 [10], 이연구에서는차이가없었다. 이는당뇨병을동반한긴관상동맥병변을가진환자비율이낮았기때문이라생각된다. 임상진단명으로 myocardial infarction가양군간에유의한차이를보인것은 I군보다 II군에서더많았음에도좋은결과를보였기때문으로생각된다. 다른연구에서는시술결과스텐트내경이더작을수록스텐트내재협착률이높은것으로보고되었으나 [30], 이연구에서는 2세대보다 1세대에서스텐트내경이더큼에도불구하고스텐트내재협착이더많이온다는결과를보였다. 이연구에서 MACE 는 2세대약물용출스텐트보다 1세대약물용출스텐트에서유의한차이를보였다. 다른연구 [31] 에서도전반적으로제1세대약물용출스텐트보다 2세대약물용출스텐트에서좋은결과를보이고있었고, 이연구역시 2세대약물용출스텐트가좋은결과를보이고있었다. 다른연구결과 MACE 발생률은 5-10% 정도였으나 [22,23,32,33], 이연구에서 1세대약물용출스텐트는 25.7%, 2세대약물용출스텐 - 197 -
- 대한내과학회지 : 제 89 권제 2 호통권제 660 호 2015 - 트는 6.6% 로서 1세대약물용출스텐트에서다소높았다. 이번연구의제한점으로는후향적조사연구였고단일센터에서시행한조사이며무작위대조시험이아니었다는점이다. 또한추적관상동맥조영술이전체대상환자의 55% 에서시행되어비교적낮은추적관상동맥조영술이시행되었다. 1세대약물용출스텐트와차이를보였던것은연도별심혈관센터방침에차이가있었기때문으로생각되어결과의해석에주의가필요하다. 그리고 1세대약물용출스텐트에서 PES가 82% 로압도적으로많은이유는그당시시술자의선호도와다혈관질환자에대한배려에의한결과라생각된다. 하지만이번연구에서는전남대학교병원심혈관센터에서시행한모든자료를보여주고자나타내었다. 또한실제임상에서는보다복잡한병변을치료하고대단위무작위연구대상에서제외되었던모든병변및환자들이치료대상에포함되는경우가많기때문에, 약물용출스텐트의중첩시술의안정성에대한결론을내리기까지는많은연구와장기간의임상관찰이필요할것으로사료된다. 2006년 1월부터 2012년 7월까지전남대학교병원심혈관센터에서긴관상동맥병변에약물용출스텐트중첩시술후 2 년임상적추적관찰환자 364명을대상으로임상경과를분석한결과, 2세대약물용출스텐트중첩시술은 1세대약물용출스텐트중첩시술보다양호한결과를보였다. 세대별스텐트의발전으로인해긴관상동맥병변에서약물용출스텐트의중첩시술은재발률및주요심장사건발생률이비교적낮은편이었지만, 향후더많은환자를대상으로연구해야할것으로생각된다. 자 364예 (63.3 ± 10.6세, 남 = 270예 ) 를대상으로하였다. 이환자중에서 1세대약물용출스텐트시술받은환자를 I군 (n = 183, 62.3 ± 10.4 세, 남 = 136예 ), 2세대약물용출스텐트시술받은환자를 II군 (n = 181, 64.3 ± 10.7세, 남 = 134예 ) 으로분류하여임상경과및주요심장사건예측인자를분석하였다. 긴관상동맥병변은 30 mm 이상병변혈관을대상으로비교하였고, 재협착은관상동맥내경이 50% 이상협착된경우로정의하였다. 결과 : 기본적임상특성에서양군간에차이가없었다. 임상진단명으로안정형협심증은 I군에서 II군보다많았고 (23.5% vs. 10.5%, p < 0.001), ST분절비상승심근경색증은 I군보다 II군에서많았다 (20.2% vs. 30.4%, p = 0.026). 미국심장학회 (ACC/AHA) 병변분류에서 I군에서 II군보다 B2형이상의복잡병변이많았다 (58.5% vs. 26.5%, p < 0.001). 주요심장사건중에서표적병변재개통률 (21.9% vs. 2.2%, p < 0.001) 은 I군에서 II군보다통계적으로유의하게높았다. 주요심장사건에미치는예측인자를파악하기위하여다변량분석 (multivariate analysis) 을한결과, 패크리탁셀용출스텐트 (PES) (HR, 5.168; 95% CI, 2.515-10.617; p < 0.001), 45% 미만의좌심실구혈률 (HR, 3.586; 95% CI, 1.839-6.990; p < 0.001), 당뇨병 (HR, 2.984; 95% CI, 1.605-5.548; p < 0.001) 이유의한예측인자이었다. 결론 : 긴관상동맥병변에약물용출스텐트중첩시술후 2년간임상결과, 2세대약물용출스텐트중첩시술은 1세대약물용출스텐트중첩시술보다양호한결과를보였다. 약물용출스텐트중첩시술후 PES, 좌심실기능저하및당뇨병이표적병변재개통률에대한발생예측인자이었다. 요 약 중심단어 : 약물용출스텐트 ; 경피적관상동맥중재술 목적 : 긴관상동맥질환은경피적관상동맥중재술의발전에도불구하고높은재협착률과좋지않은임상결과를보이고있다. 약물용출스텐트를중첩하여시술하는경우에중첩되어있는부분에는약물용출이두배로늘어나고스텐트에부착되어있는중합체에따른염증반응이나재내피화지연이주요심장사건에영향을미치는것으로알려져있다. 하지만미만성병변에대한약물용출스텐트중첩시술후장기적임상경과에대한연구가부족한실정이어서이에대한장기적임상경과를알아보고자하였다. 방법 : 대상자는 2006년 1월부터 2012년 7월까지전남대학교병원심혈관센터에서긴관상동맥병변에대하여약물용출스텐트중첩시술후 2년간임상적추적관찰이이루어진환 REFERENCES 1. Serruys PW, de Jaegere P, Kiemeneij F, et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med 1994;331:489-495. 2. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med 1994;331: 496-501. 3. Erbel R, Haude M, Höpp HW, et al. Coronary-artery stenting compared with balloon angioplasty for restenosis after initial balloon angioplasty. Restenosis Stent Study Group. N Engl J Med 1998;339:1672-1678. - 198 -
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