대한내과학회지 : 제 89 권제 3 호 2015 http://dx.doi.org/10.3904/kjm.2015.89.3.282 종설 (Review) 관상동맥스텐트의최근현황 울산대학교의과대학울산대학교병원심장내과 신은석 Current Status of Coronary Stent Eun-Seok Shin Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea Coronary artery disease is one of the principal causes of mortality worldwide. Andreas Grüntzig initially developed balloon angioplasty to treat the condition. Coronary stenting was first used in the mid-1980s to prevent abrupt vessel closure and restenosis. Stent material and design have received a great deal of attention over the past 30 years. Modern polymer stents feature antiproliferative coatings. Recently, a bioresorbable stent scaffold was introduced. This article focuses on the current status of coronary stents, especially with respect to certain aspects of clinical practice. (Korean J Med 2015;89:282-290) Keywords: Percutaneous coronary intervention; Stent; Coronary artery disease; Clinical outcome 서론 1978년 Grüntzig[1] 는관상동맥의협착병변에풍선확장술 (plain old balloon angioplasty) 을최초로시행하였다. 1980년대중반에이르러서는풍선확장술이후발생하는급성혈관폐쇄를예방하고 [2] 재협착을막기위한목적 [3] 으로관상동맥스텐트 (coronary stent) 가개발되었고, 스텐트의사용은급성합병증을예방하고임상결과를개선할수있었기에 [4] 빠르게보편화되었다. 지난 30여년간스텐트의재료및디자인, 항증식성약물의종류, 약물을코팅하는폴리머에따라수많은관상동맥용스텐트가개발되었고, 관상동맥중재시술영역에서스텐트의적용범위및선택의폭이넓어졌다. 최근에는 생체융해성스캐폴드의임상연구가활발하여곧국내에도도입될예정이다. 임상에서사용되는관상동맥스텐트및생체융해성스캐폴드에대해논의하고자한다. 본론금속그물망 (bare-metal stent) 금속그물망은풍선확장술이후발생하는급성혈관폐쇄를예방하여응급관상동맥우회술 (emergent coronary artery bypass surgery) 을줄였다. 그러나시술 2주이내에발생하는혈전성폐색이 18% 에달해항혈소판제나항혈전제의필요성이대두되었고이로인하여스텐트시술과출혈위험은필연 Correspondence to Eun-Seok Shin, M.D., Ph.D. Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan-doro, Dong-gu, Ulsan 44033, Korea Tel: +82-52-250-7056, Fax: +82-52-250-7058, E-mail: sesim1989@gmail.com Copyright c 2015 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution - 282 - 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.
- Eun-Seok Shin. Coronary stent - 성을갖게되었다 [5]. 스텐트시술은풍선확장술만시행하는데비해재협착에의한재시술을줄여주요심혈관사건의감소효과를입증하였다 [6]. 이에따라임상에서폭넓게금속그물망시술이이루어졌으며 2중항혈소판제를사용하는것이항혈전제사용보다유용하다는것도밝혀졌다 [7]. 하지만혈관손상이후에발생하는혈관평활근세포 (vascular smooth muscle cell) 의이주, 증식에의한금속그물망내신생내막의과증식 (neointimal hyperplasia) 과내경이감소한다는새로운문제점이제기되었고재협착률이 20-30% 에달하였다 [8,9]. 따라서관상동맥스텐트가갖는물리적장점에더해재협착을억제할수있는추가적인방법이연구되기시작했다. 1세대약물방출스텐트 (first generation drug-eluting stent) 약물방출스텐트는금속그물망에비해재협착을현저히줄였으며 [10,11] 복합병변이나좌주간지협착 [12] 의표준치료였던관상동맥우회술에비해사망, 심근경색, 뇌졸중등임상사건의발생측면에서별다른차이를보이지않는것으로밝혀졌다. 이런결과에힘입어약물방출스텐트를시술하게되면서관상동맥질환의치료에있어중재시술의영역이더넓어지게되었다. 1세대약물방출스텐트는 sirolimus 방출스텐트 (Cypher, Cordis, Warren, NJ, USA) 와 paclitaxel 방출스텐트 (Taxus, Boston Scientific, Natick, Massachusetts, USA) 가있다. Cypher는스테인레스스틸재질로스트럿 (strut) 의두께가 140 mm로비교적두껍고 sirolimus 가 140 m/cm 2 농도로폴리머를통해코팅되어있어 28일이내 80% 가방출된다. 1999년최초임상연구에서신생내막증식을억제하는효과를입증한뒤 [13], 무작위배정임상연구인 RAVEL연구에서비교적단순병변을가진 238명의환자를대상으로시술했을 때 1년이후금속그물망의재협착률이 26.6% 에비해 0% 라는결과를보여주었다 [14]. 이런결과는대규모복합병변을대상으로한 SIRIUS 연구를통해재시술을포함한주요심혈관사건을유의하게줄이는것으로확인되면서 [15] 당뇨, ST 상승심근경색, 만성폐색병변, 복합병변등다양한임상질환군에대한적용으로이어졌다. 메타분석을통해장기적예후를비교해볼때 Cypher는금속그물망에비해재시술을줄이는효과가있고, 사망및심근경색의발생은비슷하다 [10,11]. Taxus 는스테인레스스틸재질로 microtubule 을억제하고, G0/G1 및 G2/M 시기의세포주기를정지시키는 paclitaxel 이 100 m/cm 2 농도로폴리머를통해코팅되어있다. 비교적서서히약물이방출되어 28일이내 10% 미만이방출되며스트럿 (strut) 의두께는원래 132 mm (Taxus Express) 였으나 97 mm (Taxus Liberté) 로얇게개선되었다. Cypher 에비해구조상열린구조 (open cell) 라복합병변에서유리하며무작위배정임상연구인 TAXUS I에서 6개월째재협착의발생이없었으며 [16], ST상승심근경색 [17] 및좌주간지시술 [18] 에서금속그물망보다재시술의발생이적었다. 장기추적관찰한메타분석결과를보면, 금속그물망에비해재시술이유의하게적은장점이있다 (Table 1). Cypher와 Taxus스텐트를단기간추적, 비교한임상연구에서 Cypher가 Taxus에비해내경의감소및재협착의발생측면에서더우수하다고보고하였다 [19,20]. 16개의임상연구를메타분석하여 2년간의임상결과를비교해보면 Cypher 가병변의재시술 ( 위험도 : 0.74, 95% 신뢰구간 0.63-0.87, p < 0.001) 및스텐트혈전증 ( 위험도 : 0.66, 95% 신뢰구간 0.46-0.94, p = 0.02) 의위험도를낮추나사망 ( 위험도 : 0.92, 95% 신뢰구간 0.74-1.13, p = 0.43) 및심근경색 ( 위험도 : 0.84, 95% 신뢰구간 0.69-1.03, p = 0.10) 의발생에서는차이가없었다 [21]. Table 1. A comparison between drug-eluting and bare-metal stents First author Number of patients Follow up (yr) Drug-eluting stent compared to bare metal stent Death Myocardial infartion Revascularization Sirolimus eluting stent and bare metal stent Stettler et al. [22] 8,646 4 Hazard ratio: 1.0 Hazard ratio: 0.81 a Hazard ratio: 0.3 b Stone et al. [26] 1,748 4 6.7% vs. 5.3% 6.4% vs. 6.2% 7.8% vs. 23.6% b Kastrati et al. [10] 4,958 5 6.0% vs. 5.9% 9.7% vs. 10.2% c Hazard ratio: 0.43 b Paclitaxel eluting stent and bare metal stent Stettler et al. [22] 8,330 4 Hazard ratio: 1.03 Hazard ratio: 1.0 Hazard ratio: 0.42 b Stone et al. [26] 3,513 4 6.1% vs. 6.6% 7.0% vs. 6.3% 10.1% vs. 20.0% b a p < 0.05. p < 0.001. c Incidence of death and myocardial infarction. - 283 -
- 대한내과학회지 : 제 89 권제 3 호통권제 661 호 2015 - 약물방출스텐트 (drug-eluting stent) 의장단점 약물방출스텐트의가장중요한장점은재협착에의한재시술을감소시킨다는것이다. 38개의임상연구에대한메타분석 [22] 에서 4년간추적관찰했을때약물방출스텐트는금속그물망보다는 Cypher 의경우 70%, Taxus의경우 58% 재협착에의한재시술을감소시켰고 34개의관찰연구를메타분석하여실제임상에서사용된병변을대상으로하더라도금속그물망에비해재시술 ( 위험도 : 0.54, 95% 신뢰구간 0.48-0.61) 감소를입증하였다 [23]. 하지만약물방출스텐트의임상경험이쌓이면서 2006년 BASKET-LATE 연구 [24] 와 SCAAR 등록연구 [25] 에서 10-30% 의치사율을보이는스텐트혈전증의문제가제기되었다 (Fig. 1). 시술 1개월이내발생하는조기스텐트혈전증 (early stent thrombosis) 이나 1개월에서 1년사이발생하는후기스텐트혈전증 (late stent thrombosis) 은 2중항혈소판제의조기중단이나작은사이즈의스텐트시술, 병변길이가 28 mm 이상인경우, 여러스텐트시술, 석화화및작은혈관의시술과관련이있는것으로보고되며 [24], 금속그물망과약물방출스텐트의발생률차이는없었다. 하지만약물방출스텐트의경우지속적으로스텐트혈전증이발생하여 (0.5-0.6%/ 년 ) 1년이후발생하는스텐트혈전증 (very late Figure 1. Coronary angiography evidencing late thrombosis in a drug-eluting stent. Late stent thrombosis was evident upon coronary angiography (arrows indicate a filling defect in the proximal portion of the left anterior descending coronary artery). Thrombosis developed after cessation of aspirin therapy. stent thrombosis) 은금속그물망보다유의하게발생률이높았다 [22,25,26]. 이는항증식약물및폴리머에의해스텐트부위가혈관내피세포로덮이는과정이지연되고 (delayed endothelization) [27,28] 과민반응 (hypersensitivity reaction) [29] 이발생하기때문으로여겨져, 혈관재생을개선한약물방출스텐트를고안하는계기가되었다. 2세대약물방출스텐트 (second generation drug-eluting stent) 기존스텐트의재료물질인스테인레스스틸을대체하여방사상강도 (radial strength) 가크고방사선비투과성인코발트크롬 (cobalt chromium) 이이용되면서스트럿이더얇아지고, limus 계통의항증식약물을사용하며, 생체적합성이개선된폴리머를사용한것이특징이다. 대표적으로 zotarolimus 방출 Endeavor (Medtronic Cardiovascular, Santa Rosa, CA, USA) 및 Resolute (Medtronic Cardiovascular, Santa Rosa, CA, USA) 스텐트와 everolimus 방출 Xience (Abbott Vascular, Santa Clara, CA, USA) 스텐트가있으며, 현재중재시술분야에서주로사용된다. Endeavor는세포막성분인포스포콜린폴리머를이용, 시술 14일이내에 95% 이상의 zotarolimus 가방출되어염증반응이 Cypher보다덜하다 [28]. Endeavor와금속그물망을비교한 ENDEAVOR II 연구 [30] 에서스텐트내내경감소및재협착발생측면에서우수한결과를보였으며 5년간추적관찰에서재시술률이더낮았고, 사망, 심근경색및스텐트혈전증은유사하였다 [31]. Endeavor는 1세대약물방출스텐트인 Cypher/Taxus와비교할때 12개월째내경감소측면에서불리한결과를보이나 [32,33], 재시술측면에서격차는 5년째감소하여후기따라잡이 (late-catch) 현상이없는것을알수있다. 우리나라의단일기관에서시행된 Endeavor, Cypher, Taxus 무작위배정, 비교연구, ZEST [34] 에서는 12개월째사망, 심근경색, 허혈로인한재시술을포함한복합임상사건의발생이 10.2% 로 Cypher 8.3%, Taxus 14.1% 로 Cypher 보다는비열등하고 (p = 0.01), Taxus보다우수한 (p = 0.01) 결과를보였다. ZEST 연구에서 12개월째스텐트혈전증의발생은 0.7% 로, Cypher 0%, Taxus 0.8% 와유사하였으나드물게발생하는스텐트혈전증의차이를알기에는대상환자의수가부족하고, 2세대약물방출스텐트를고안하게된계기가된 1년이후의스텐트혈전증 (very late stent thrombosis) 의발생을비교하기에는제한적이다. 모든시술환자 (all-comer), 8,800 명을대상으로 Endeavor와 Cypher 를무작위배정하는임상연구, PROTECT가진행되었으나 [35] 2012년유럽심장학회에서 - 284 -
- 신은석. 관상동맥스텐트 - 1년이후발생하는스텐트혈전증 (very late stent thrombosis) 의발생에별다른차이가없다고발표된후출간되지는않았다. Xience는 100 mg/cm 2 의 everolimus 가 6-8 mm 두께의생체적합성폴리머에서 30일내에 80% 까지방출된다. Xience 스텐트는 1세대약물방출스텐트인 Taxus와비교한 SPIRIT II/III 연구에서 6-12개월째내경의감소가덜하고 [36,37], 1년간추적관찰했을때, 재시술의감소에따른복합임상사건의발생이유의하게적은것으로보고되었다 [38]. 고무적인것은 COMPARE 연구 [39] 에서 12개월째스텐트혈전증의발생이 Xience 치료군에서 0.7% 로 Taxus 치료군의 2.6% 보다유의하게낮다는점이다. 생융해성폴리머약물방출스텐트시술후 6-9개월째융해되는생융해성폴리머를이용한 biolimus 방출스텐트로 Biomatrix (Biosenors, Morges, Swizerland) 와 Nobori (Terumo, Tokyo, Japan) 가있다. Biomatrix 는 LEADERS 연구에서 9개월째심장관련사망, 심근경색및목표혈관재시술등복합임상사건의발생에있어 Cypher에비해비열등하였고 [40], 4년째비슷한결과를보여주었다 [41]. 특히, 주목할것은 1년이후발생하는스텐트혈전증의발생률이 1% 로 Cypher의 2% 에비해유의하게 (p = 0.005) 낮다는점이다. 후기따라잡이현상 (late catch) 의원인으로지목되기때문에 [45] 염증반응이적은것또한생체융해성스캐폴드의장점이된다 [46]. 아직까지임상연구결과가제한적으로 Communaut' Europeen 인증및임상에서사용가능한것은 Absorb (Abbott Vascular, Santa Clara, CA, USA) 와 DESolve (Elixir Medical Corporation, Sunnyvale, CA, USA) 가있으며, 안정성과유효성측면에서추가적인연구가필요한상황이다. Magnesium stent 마그네슘은큰방사상강도 (radial strength) 로시술후반동 (recoil) 이적고추가확장 (post-dilatation) 을하더라도골절이잘생기지않는금속성성질을띄고있어생체융해성스캐폴드의재료로일찍부터주목을받아연구가진행되었다 (Fig. 2). 융해반응시표면이미란되어점차얇아지므로일정기간동안충분히수축재형성 (negative remodeling) 에저항하기어렵다는문제점이있으며인간대상최초연구 (PROGRESS-AMS trial) [45] 는 AMS-1 (Biotronik, Berlin, Germany) 로진행되었는데마그네슘스캐폴드가빠른속도로융해되어 4개월째재협착률이 50% 에달하고, 1년째재시술률이 45% 로결과가좋지않았다. 따라서융해속도를지연시키기위해지르코늄및이 생체융해성스캐폴드 (bioresorbable scaffold) A B 생체융해성스캐폴드는풍선확장술후발생하는내막손상및박리로인한급성폐색을스캐폴드를이용하여방지, 3-6개월의일정기간동안혈관내경을유지하여수축재형성 (negative remodeling) 을막고 [42], 항증식약물의방출로내막의과증식을방지하여재협착을예방한다 [43]. 기존스텐트의재료인금속과다른재료로만들어져혈관의고유한특성을유지하고, 후기혈전증 (late thrombosis) 의위험성을낮추고자개발되었다 [44]. 생체내융해과정을통해혈관내피세포로시술병변이덮이는과정을통해후기혈전증의위험성이낮아지고, 젋은연령의환자에서향후추가적인관상동맥중재시술이나관상동맥우회술이용이하다. 특히재료가금속이아니기때문에인공음영 (artifact) 없이컴퓨터단층촬영 (computed tomography) 이나자기공명영상 (magnetic resonance imaging) 으로추적검사가가능하며, 혈관확장및연축기능을유지 (vasomotion) 함으로써박동성혈류 (pulsatile flow) 및전단스트레스 (shear stress) 에반응하여혈관의확장성재형성 (positive remodeling) 이가능하다. 그밖에도금속그물망시술이후지속적인염증반응은신생죽종 (neo-atheroma) 발생과 Figure 2. Absorbable magnesium stents (AMSs). (A) AMS-1; The first-generation magnesium stent featured sinusoidal hoops; adjacent hoops were linked by three straight bridges. (B) AMS-3; The next-generation magnesium stent was modified by the addition of zirconium and yttrium, and was drug-eluting (the drug was paclitaxel). - 285 -
- The Korean Journal of Medicine: Vol. 89, No. 3, 2015 - 트륨을마그네슘에첨가하였고, paclitaxel 을 3개월에걸쳐방출하도록 1 μm 두께로 polylactic-co-glycolic acid 폴리머를이용하여코팅한 AMS-3 가개발되었다. AMS-3 를이용한전향적, 인간대상연구는 BIOSOLVE-1 연구 (Biotroniks Safety and Clinical Performance of the First Drug- Eluting Generation Absorbable Metal Stent in Patients with de Novo Lesions in Native Coronary Arteries) [47] 로 46명환자의단순병변에서시술되어 6개월째 2명 (4.3%) 의재시술외에사망이나혈전증은발생하지않았다. 6개월째와 12개월째후기내강소실 (late lumen loss) 은 0.65 ± 0.5 mm, 0.39 ± 0.33 mm의결과를보였다. ABSORB everolimus-eluting bioresorbable vascular scaffold Absorb BRS (Abbott Vascular, Santa Clara, CA, USA) 는 poly-l-lactic acid를주재료로하여이용하고, 항증식약물인 everolimus 를 poly-d, L-lactide로코팅하여방출하도록개발되었다. poly-l-lactic acid는 lactide로가수분해되었다가 Krebs cycle을통해이산화탄소및물로대사되며 2 μm보다작은입자는대식구에의해탐식된다. 스캐폴드의구조는 3차례변경되었으며 (Fig. 3) 급성반동 (acute recoil) 은 Xience 스텐트와유사하다 [48]. 1세대 Absorb 를이용하여단순병변을가진 30명의환자를대상으로 5년간추적관찰한 Cohort A 연구 [49] 에서주요임상사건의발생은단 1명이었다. 혈관내초음파 (intravascular ultrasound, IVUS) 에서 6개월째스캐폴드의쭈그러듦 (shrinkage) 소견에도불구하고후기내강소실 (late lumen loss) 0.44 mm 로확인되었으며, 6개월에서 2년사이스캐폴드크기의변화가없었음에도내강이커진것으로혈관내초음파 (IVUS) 및광간섭성단층촬영 (optical coherence tomography) 을통해관 A B C Figure 3. The ABSORB everolimus-eluting bioresorbable vascular scaffold. (A) The first-generation bioresorbable vascular scaffold features paired out-of-phase sinusoidal hoops directly linked at each peak and valley. Each pair is in turn linked using three straight connectors. This design was used in Cohort A of the ABSORB trial. (B) The second-generation Absorb scaffold, tested in Cohort B of the ABSORB trial, features in-phase sinusoidal hoops linked at the peaks and valleys by three straight connectors. All three Absorb scaffolds carry radiopaque platinum markers at either end (arrow). (C) The third-generation stent (the commercialized version) features small changes to the shape of the bends in the hoops and to the strut thickness and width. Also, certain changes in the manufacturing process facilitate later post-dilation to a larger diameter without tissue damage. Strut thickness is increased from 150 to 155 μm and strut width from 163 to 188 μm in the 2.5- and 3.0-mm-diameter third-generation Absorb devices, respectively; the 3.5-mm-diameter third-generation device has a strut thickness of 155 μm and a strut width of 213 μm. The 3.0-mm-diameter third-generation scaffold can be safely post-dilated to 3.5 mm, and the 3.5-mm-diameter device to 4.0 mm. - 286 -
- Eun-Seok Shin. Coronary stent - 찰되었다 [43]. 특히혈관의생리적인기능이회복되어질산염투여시혈관이확장하고에르고노빈 (ergonovine) 투여시혈관이수축하는반응이확인되었다. 2세대 Absorb 는가수분해의속도를늦추도록고안되어 101명의환자를대상으로 Cohort B 연구 [50] 에서적용되었다. 2년째주요임상사건의발생은 6.8% 였고, 후기내강소실은 0.27 mm로 Xience 스텐트와유사한결과를보여주었다. 혈관내초음파및광간섭성단층촬영에서 6개월에서 2년사이혈관의양성재형성 (positive remodeling) 및스캐폴드의크기가증가되면서신생내막의증가를감쇄하여실제내강의감소는거의없는것으로확인되었다 [51]. 단순병변에서 2세대약물방출스텐트인 Xience와 Absorb 를무작위배정하여 2년째혈관확장및연축기능의유지 (vasomotion) 및최소내강직경 (minimum luminal diameter) 을비교하는 ABSORB II 연구 (clinicaltrials.gov identifier, NCT01425281) 가진행중이며 1년째중간분석에서임상사건발생이 3% 대 5% 로유사한것으로발표되었다 [52]. 미국식약청 (U.S. Food and Drug Administration) 의허가를위해대규모무작위배정, 임상연구인 ABSORB III 연구 (clinicaltrials. gov identifier, NCT01751906) 와다기관등록연구로 ABSORB Extend 연구 (clinicaltrials.gov identifier, NCT01023789) 가진행되어결과를기다리고있다. REVA bioabsorbable stent 1세대 REVA (Reva Medical, San Diego, CA, USA) BRS는약물을방출하지않는형태로 27명의환자를대상으로 RESORB 연구에서적용되었으나스캐폴드의문제로인해 4-6개월째재시술이많았다. 이를개선하고자스캐폴드디자인 (slide-lock, ratchet) 및중합체 (tyrosine-derived polycarbonate polymer) 의가공공정의개선, sirolimus 방출하도록하여 ReZolve BRS가개발되었다 (Fig. 4). 아직최초임상시험의결과가보고되지않았으나 50명의환자를대상으로 RESTORE 연구 (clinical trials.gov identifier, NCT01262703) 가진행중이다. DESolve bioresorbable scaffold DESolve (Elixir Medical Corporation, Sunnyvale, CA, USA) 스캐폴드는 poly-l-lactic acid 중합체로구성되며구조는그림 5와같다. 3 mm 두께로 poly-d, L-lactide가코팅되어 sirolimus 의대사물인 myolimus (Novartis, Basel, Switzerland) 또는 novolimus (Elixir Medical, Sunnyvale, CA, USA) 를방출한다. DESolve First-in-Man 연구 [53] 는 myolimus 방출스캐폴드를단순병변을가진 16명의환자에적용하여 6개월째조영술에서비교적좋은후기내강소실, 0.19 mm를보여주었고, 1명의환자에서재시술이발생하였다. 현재는 120명의환자를대상 A B Figure 4. The REVA bioabsorbable stent. (A) The REVA bioresorbable scaffold features a unique slide-and-lock mechanism (black and white arrows) that permits the lumen of the scaffold to be enlarged without concentrating strain on the hinge points (unlike standard polymeric scaffolds). After expansion of the ReZolve scaffold, the locking mechanism maintains the expansion and affords radial strength. (B) An optical coherence tomography image. The strut (thickness, 120 μm) is indicated by the black arrow; the white arrow indicates the ratchet (strut thickness, 250 μm). - 287 -
- 대한내과학회지 : 제 89 권제 3 호통권제 661 호 2015 - A B C Figure 5. The DESolve stent (Elixir Medical Corporation, Sunnyvale, CA, USA). (A) The balloon-mounted scaffold (black arrow); radiopaque markers (white double arrow). A gap is evident gap between the balloon marker (M) and the scaffold. (B) The scaffold features in-phase sinusoidal hoops linked by three straight connectors. (C) A scaffold post-dilated to a diameter of 4.75 mm without strut fracture. 으로 novolimus를방출하는스캐폴드를이용한무작위배정임상연구가진행중이다. 결론 1980년대부터 30여년간관상동맥스텐트의변천사를살펴보면기존의스텐트가갖는문제점을찾아내고개선하여더나은임상결과를얻고자했던노력을엿볼수있다. 흥미로운점은오래전개발된금속그물망은임상상황에따라여전히시술되고있는데반해, 1세대약물방출스텐트인 Cypher와 Taxus는강력한신생내막증식억제효과로각광을받았음에도스텐트혈전증과같은안전성의문제로더이상시술되지않는다는점이다. 현재우리나라에서는 2세대약물방출스텐트가주로사용되지만생융해성폴리머를갖는약물방출스텐트가좋은임상결과를보여주고있으며, 국내에곧도입될생체융해성스캐폴드의비중도늘어날전망이다. 생체융해성스캐폴드의경우아직까지시술경험이없고, 분지부나만성폐색및좌주간지등의복합병변에대한임상결과가부족하다. 하지만스텐트시술이후의장기적인안전성을고려하고생체융해성스캐폴드시술후혈관고유의기능을유지하여예후를개선하는결과와이어진다면관상동맥스텐트의변천사에큰갈림길이될것이다. 중심단어 : 경피적관상동맥중재술 ; 스텐트 ; 관상동맥질환 ; 임상결과 REFERENCES 1. Grüntzig A. Transluminal dilatation of coronary-artery stenosis. Lancet 1978;1:263. 2. Roubin GS, Cannon AD, Agrawal SK, et al. Intracoronary stenting for acute and threatened closure complicating percutaneous transluminal coronary angioplasty. Circulation 1992;85:916-927. 3. 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. 4. Schatz RA, Baim DS, Leon M, et al. Clinical experience with the palmaz-schatz coronary stent. Initial results of a multicenter study. Circulation 1991;83:148-161. 5. van Domburg RT, Foley DP, de Jaegere PP, et al. Long term outcome after coronary stent implantation: A 10 year single centre experience of 1000 patients. Heart 1999;82 Suppl 2:II27-34. 6. 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. 7. Schomig A, Neumann FJ, Kastrati A, et al. A randomized - 288 -
- 신은석. 관상동맥스텐트 - comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996; 334:1084-1089. 8. Hoffmann R, Mintz GS, Dussaillant GR, et al. A serial intravascular ultrasound study. Circulation 1996;94:1247-1254. 9. Gordon PC, Gibson CM, Cohen DJ, Carrozza JP, Kuntz RE, Baim DS. Mechanisms of restenosis and redilation within coronary stents--quantitative angiographic assessment. J Am Coll Cardiol 1993;21:1166-1174. 10. Kastrati A, Mehilli J, Pache J, et al. Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med 2007;356:1030-1039. 11. Spaulding C, Daemen J, Boersma E, Cutlip DE, Serruys PW. A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med 2007;356:989-997. 12. 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; 360:961-972. 13. Sousa JE, Costa MA, Abizaid AC, et al. Sustained suppression of neointimal proliferation by sirolimus-eluting stents: One-year angiographic and intravascular ultrasound follow-up. Circulation 2001;104:2007-2011. 14. 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: 1773-1780. 15. 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;349:1315-1323. 16. Grube E, Silber S, Hauptmann KE, et al. TAXUS I: six- and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions. Circulation 2003;107:38-42. 17. Stone GW, Lansky AJ, Pocock SJ, et al. Paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction. N Engl J Med 2009;360:1946-1959. 18. Erglis A, Narbute I, Kumsars I, et al. A randomized comparison of paclitaxel-eluting stents versus bare-metal stents for treatment of unprotected left main coronary artery stenosis. J Am Coll Cardiol 2007;50:491-497. 19. Morice MC, Colombo A, Meier B, et al. Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial. JAMA 2006; 295:895-904. 20. Lee SW, Park SW, Kim YH, et al. A randomized comparison of sirolimus- versus paclitaxel-eluting stent implantation in patients with diabetes mellitus. J Am Coll Cardiol 2008;52: 727-733. 21. Schömig A, Dibra A, Windecker S, et al. A meta-analysis of 16 randomized trials of sirolimus-eluting stents versus paclitaxel-eluting stents in patients with coronary artery disease. J A Coll Cardiol 2007;50:1373-1380. 22. Stettler C, Wandel S, Allemann S, et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. Lancet 2007;370:937-948. 23. Kirtane AJ, Gupta A, Iyengar S, et al. Safety and efficacy of drug-eluting and bare metal stents: Comprehensive metaanalysis of randomized trials and observational studies. Circulation 2009;119:3198-3206. 24. Wenaweser P, Daemen J, Zwahlen M, et al. Incidence and correlates of drug-eluting stent thrombosis in routine clinical practice. 4-year results from a large 2-institutional cohort study. J Am Coll Cardiol 2008;52:1134-1140. 25. Roukoz H, Bavry AA, Sarkees ML, et al. Comprehensive meta-analysis on drug-eluting stents versus bare-metal stents during extended follow-up. Am J Med 2009;122:581.e1-e10. 26. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med 2007;356:998-1008. 27. Joner M, Nakazawa G, Finn AV, et al. Endothelial cell recovery between comparator polymer-based drug-eluting stents. J Am Coll Cardiol 2008;52:333-342. 28. Kim JS, Jang IK, Kim JS, et al. Optical coherence tomography evaluation of zotarolimus-eluting stents at 9-month follow-up: Comparison with sirolimus-eluting stents. Heart 2009;95:1907-1912. 29. 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; 109:701-705. 30. Fajadet J, Wijns W, Laarman GJ, et al. Randomized, doubleblind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions: clinical and angiographic results of the ENDEAVOR II trial. Circulation 2006;114:798-806. 31. Fajadet J, Wijns W, Laarman GJ, et al. Long-term follow-up of the randomised controlled trial to evaluate the safety and efficacy of the zotarolimus-eluting driver coronary stent in de novo native coronary artery lesions: five year outcomes in the ENDEAVOR II study. EuroIntervention 2010;6:562-567. 32. Kandzari DE, Leon MB, Popma JJ, et al. Comparison of zotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease: a randomized controlled trial. J Am Coll Cardiol 2006;48:2440-2447. 33. Leon MB, Mauri L, Popma JJ, et al. A randomized comparison of the Endeavor zotarolimus-eluting stent versus the - 289 -
- The Korean Journal of Medicine: Vol. 89, No. 3, 2015 - TAXUS paclitaxel-eluting stent in de novo native coronary lesions 12-month outcomes from the ENDEAVOR IV trial. J Am Coll Cardiol 2010;55:543-554. 34. Park DW, Kim YH, Yun SC, et al. Comparison of zotarolimus-eluting stents with sirolimus- and paclitaxel-eluting stents for coronary revascularization: the ZEST (comparison of the efficacy and safety of zotarolimus-eluting stent with sirolimus-eluting and paclitaxel-eluting stent for coronary lesions) randomized trial. J Am Coll Cardiol 2010;56:1187-1195. 35. Camenzind E, Wijns W, Mauri L, et al. Rationale and design of the patient related outcomes with endeavor versus cypher stenting trial (protect): Randomized controlled trial comparing the incidence of stent thrombosis and clinical events after sirolimus or zotarolimus drug-eluting stent implantation. Am Heart J 2009;158:902-909.e5. 36. Serruys PW, Ruygrok P, Neuzner J, et al. A randomised comparison of an everolimus-eluting coronary stent with a paclitaxel-eluting coronary stent:the SPIRIT II trial. Euro- Intervention 2006;2:286-294. 37. Stone GW, Midei M, Newman W, et al. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial. JAMA 2008;299:1903-1913. 38. Stone GW, Rizvi A, Newman W, et al. Everolimus-eluting versus paclitaxel-eluting stents in coronary artery disease. N Engl J Med 2010;362:1663-1674. 39. Kedhi E, Joesoef KS, McFadden E, et al. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet 2010;375: 201-209. 40. Windecker S, Serruys PW, Wandel S, et al. Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial. Lancet 2008; 372:1163-1173. 41. Stefanini GG, Kalesan B, Serruys PW, et al. Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (leaders): 4 year followup of a randomised non-inferiority trial. Lancet 2011;378: 1940-1948. 42. Serruys PW, Luijten HE, Beatt KJ, et al. Incidence of restenosis after successful coronary angioplasty: A time- related phenomenon. A quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months. Circulation 1988; 77:361-371. 43. Serruys PW, Ormiston JA, Onuma Y, et al. A bioabsorbable everolimus-eluting coronary stent system (absorb): 2-year outcomes and results from multiple imaging methods. Lancet 2009;373:897-910. 44. Nishio S, Kosuga K, Igaki K, et al. Long-term (>10 years) clinical outcomes of first-in-human biodegradable poly-llactic acid coronary stents: Igaki-tamai stents. Circulation 2012;125:2343-2353. 45. Erbel R, Di Mario C, Bartunek J, et al. Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial. Lancet 2007; 369:1869-1875. 46. Onuma Y, Serruys PW, Perkins LE, et al. Intracoronary optical coherence tomography and histology at 1 month and 2, 3, and 4 years after implantation of everolimus-eluting bioresorbable vascular scaffolds in a porcine coronary artery model: An attempt to decipher the human optical coherence tomography images in the absorb trial. Circulation 2010; 122:2288-2300. 47. Haude M, Erbel R, Erne P, et al. Safety and performance of the drug-eluting absorbable metal scaffold (DREAMS) in patients with de-novo coronary lesions: 12 month results of the prospective, multicentre, first-in-man BIOSOLVE-I trial. Lancet 2013;381:836-844. 48. Tanimoto S, Serruys PW, Thuesen L, et al. Comparison of in vivo acute stent recoil between the bioabsorbable everolimus-eluting coronary stent and the everolimus-eluting cobalt chromium coronary stent: Insights from the absorb and spirit trials. Catheter Cardiovasc Interv 2007;70:515-523. 49. Ormiston JA, Serruys PW, Regar E, et al. A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial. Lancet 2008;371:899-907. 50. Ormiston JA, Serruys PW, Onuma Y, et al. First serial assessment at 6 months and 2 years of the second generation of absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study. Circ Cardiovasc Interv 2012;5:620-632. 51. Simsek C, Karanasos A, Magro M, et al. Long-term invasive follow-up of the everolimus-eluting bioresorbable vascular scaffold: five-year results of multiple invasive imaging modalities. EuroIntervention 2014 Oct 28. [Epub ahead of print] 52. Serruys PW, Chevalier B, Dudek D, et al. A bioresorbable everolimus-eluting scaffold versus a metallic everolimuseluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial. Lancet 2015;385:43-54. 53. Verheye S, Ormiston JA, Stewart J, et al. A next-generation bioresorbable coronary scaffold system: from bench to first clinical evaluation: 6- and 12-month clinical and multimodality imaging results. JACC Cardiovasc Interv 2014;7:89-99. - 290 -