<303520C1BEBCB320B9DABDC2C1A42E687770>

Transcription

1 대한내과학회지 : 제 81 권제 5 호 2011 종설 (Review) 좌주간부관상동맥질환에서경피적중재시술의현재와미래전망 울산대학교의과대학서울아산병원심장내과 박승정 박덕우 Current Status and Future Perspective of Left Main Coronary Intervention Seung-Jung Park and Duk-Woo Park Division of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea For several decades, based on clinical trials comparing coronary-artery bypass grafting (CABG) with medical therapy, bypass surgery has been regarded as the treatment of choice for patients with unprotected left main coronary artery (LMCA) disease. However, because of marked advancements in techniques of percutaneous coronary intervention (PCI) with stenting and CABG and adjunctive pharmacologic therapy, new evaluation and a review of current indications for optimal revascularization therapy for LMCA disease may be required to determine the standard of care for these patients. The available current evidence suggests that the composite outcome of death, myocardial infarction and stroke is similar in patients with LMCA disease who are treated with PCI with stenting or CABG, only difference was the rate of repeat revascularization. Cumulative and emerging data from several extensive registries and a large clinical trial may have prompted many interventional cardiologists to select PCI with stenting as an alternative revascularization strategy for such patients. In addition, these data may change future guidelines and support the need for prospective, large randomized trials comparing the two revascularization treatment. Finally, these evidence will change the current clinical practice of revascularization strategy for unprotected LMCA disease. (Korean J Med 2011;81: ) Keywords: Bypass surgery; Stents; Left main coronary disease 과거 20년전시행된관상동맥우회술과약물치료의비교연구의결과에기반하여보호받지않는좌주간부병변 (unprotected left main coronary artery disease) 의표준치료로서관상동맥우회수술이표준치료로최근까지자리매김해왔다 [1,2]. 좌주간부는해부학적으로접근이용이하며상대적으로큰직경을가지고있어, 이부위에서경피적관상동맥중재술의적용은중재시술분야의심장전문의에게매우흥미 로운도전분야로여겨졌다. 최근수년동안의관상동맥시술분야의진보와보조적약물치료의발전에힘입어좌주간부협착에서의중재시술이각광을받고있으며, 약물용출스텐트의도입후에보호되지않는좌주간부병변의대체치료로서관상동맥중재술의의미가재해석되고있다 [3]. 하지만아직까지좌주간부병변에대한관상동맥중재술과관상동맥우회수술간의임상연구및장기적결과가매우미 Correspondence to Seung-Jung Park, M.D., Ph.D. Division of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Pungnap-dong, Songpa-gu, Seoul , Korea Tel: , Fax: , sjpark@amc.seoul.kr

2 - The Korean Journal of Medicine: Vol. 81, No. 5, 흡한것이사실이다. 이에저자는최근까지의문헌고찰을통하여좌주간부병변에대한표준치료의대안으로관상동맥중재술의현재의미와미래에대해고찰해보고자한다. 스텐트를이용한관상동맥중재술의결과 지난수년동안, 좌주간부병변에서일반스텐트 (bare-metal stent) 를이용한관상동맥중재술은중ㆍ단기결과에서그가능성을보여주었다. 이러한경험을초석으로약물용출스텐트가개발되었고, 일반금속스텐트의단점이보완되면서경험이풍부한중재시술자들은현재보호되지않는좌주간부병변에대해중재시술을널리시행하고있다. 여러비무작위관찰연구의결과를살펴보면, 소규모의단기결과임을감안하더라도, 일반스텐트에비해약물용출스텐트의결과가낙관적임을알수있다 [4-7]. 최근, 보호되지않은좌주간부병변에서약물용출스텐트와일반스텐트를비교한대규모의메타분석이보고되었다 [8]. 44개의연구에서, 일반스텐트나약물용출스텐트를시술받은 10,342명의환자가분석되었다. 3년째각사건의누적발생률은사망은일반스텐트사용군에서 12.7%, 약물용출스텐트사용군에서 8.8% 의비율을보였으며심근경색은각각 3.4% 와 4.0%, 표적혈관재관류또는표적병변재관류는각각 16.4% 와 8.0%, 주요심장사건은 31.6% 와 21.4% 으로나타났다. 각임상사건별스텐트종류에다른보정위험도는그림 1에기술되어있다. p value Figure 1. Adjusted odds ratio for 3-year outcomes of drugeluting versus bare-metal stents in unprotected left main coronary artery stenosis. MI, myocardial infarction; TLR, target-lesion revascularization; TVR, target-vessel revascularization; MACE, major adverse cardiac events. 개구부및체부좌주간부병변 (ostial and/or shaft disease) 좌주간부병변에서스텐트삽입술의성공과실행가능성여부를판단하기위해선우선좌주간부병변의해부학적특징이면밀히검토되어야한다. 또한관상동맥경화반이좌주간부의개구부내분포여부, 좌주간부의길이및좌주간부말단에위치하여좌전하행지나좌회선지까지침범하면서분지부의혈류를막는경화반의범위도확인하여시술의적용가능성을가늠해봐야한다. 약물용출스텐트의사용으로인한재협착의괄목할만한감소와접근용이성으로인해중재시술의성공가능성이높아짐에따라, 좌주간부개구부및체부병변에대한중재시술은매력적인시술대상이되어왔다. 최근발표된다기관관찰연구에서시술성공률이환자의 99% 에이르며, 입원중 Q-wave 심근경색이나사망이발생하지않고, 재협착및조영술상후기스텐내직경의후기소실이 0.01 mm 및재협착률이 0.9% 으로낮아약물방출스텐트의장기성적이양호함을보여주고있다 [9]. 또한 2년여의임상관찰동안누적사망률은 3.4%, 목표혈관재개통률은 4.7% 로양호하였다. 말단분지부병변좌주간부병변이있는환자의절반이상 (60-90%) 은분지부말단에병변이존재한다. 여러연구에서좌주간부말단에서단일스텐스시술의결과가두개이상의스텐트를이용한복합스텐트시술보다임상경과가우수함을증명하였다 [10,11]. 말단분지부에병변이있다하더라도단일스텐트를이용한중재술시목표병변재협착의발생비율이매우낮으며 (< 5%), 이는좌주간부개구부와중간부에서의성적과거의유사하다 [4-6]. 그러나좌주간부말단병변을 2개이상의스텐트로치료한복합스텐트시술시목표병변재협착의발생이 25% 까지증가하며, 이때재협착은좌회선지의개구부에주로발생하는것으로알려져있다. 최근보호되지않은좌주간부병변에약물용출스텐트를시술받은 1,111 환자를대상으로한대규모관찰연구에 [12] 따르면개구부와중간부병변에비하여말단분지부좌주간부병변에서 50% 이상더많은임상사건이발생하였으며특히분지부에서복잡하게스텐트를삽입한경우에더욱그런경향을보였다. 하지만, 단일스텐트시술을받은경우와개구부또는중간부병변에서시술을받은경우와의비교에서는유의한임상사

3 - Seung-Jung Park, et al. Current status and future perspective of left main coronary intervention - 건차이를보이지않았다. 좌주간기병변중재술의안전성약물용출스텐트를이용한관상동맥중재술이광범위하게이용됨에따라장기적안전성, 특히후기스텐트혈전과사망률등에대한관심도높아지고있다 [13-15]. 이와관련하여보호되지않은좌주간부병변에서의스텐트삽입술후스텐트혈전증발생시직접적으로돌연사의위험을높일수있다는우려와장기적인임상자료의부족으로약물용출스텐트를이용한중재술이좌주간부병변에서관상동맥우회술을대체하는방법으로의선택에주저함있는것이사실이다. 하지만, 최근발표된보호되지않는좌주간부병변에서약물용출스텐트을이용한중재술의안전성에대한결과들은이러한우려를약화시키고있다 [16-19]. 여러대규모관찰연구의결과를살펴보면좌주간부에서 1-3년이내발생하는스텐트혈전증의빈도는약 1-2% 정도이며, 이는통상적으로실제임상에서좌주간부가아닌다른관상동맥부위의스텐트삽입술이후발생하는스텐트혈전증의빈도와유사하거나오히려낮은빈도라할수있다. 또한 1세대보다효용성과안정성이뛰어난 2,3세대스텐트를 [20,21] 사용이이러한장기안정성에대한우려가많이감소될것으로판단된다. 스텐트를이용한중재술의기술적인측면분획혈류예비력 (fractional flow reserve, FFR) 을이용한진단 (decision-making) 최근다혈관관상동맥질환에서분획혈류예비력을이용한관상동맥중재술시행을결정하는것이주요심장사건의발생을줄일수있다는연구결과들이발표되고있다 [22]. 이전연구결과에따르면좌주간부질환에서 FFR이 이상이면장기관찰의예후가양호한것이증명되었다 [23-25]. Jasti 등은 FFR이 0.75 미만인군 ( 혈관개통술시행군 ) 과이상인군 ( 약물치료군 ) 사이에 38개월간생존율 (100% vs. 100%, p > 0.05) 과무사건생존율 (event-free survival) 에서유의한차이가없음 (100% vs. 90%, p > 0.05) 을보고하였다 [23]. 또한좌주간부협착이모호한경우, FFR 0.80을기준으로치료효과를비교한연구에서는 FFR이 0.80 미만에서우회수술을받은경우와 0.80 이상에서약물치료를한군사이에 서두군간에 5년생존율 (85.4% vs. 89.8%, p = 0.48) 과 5년무사건생존율 (74.2% vs. 82.8%, p = 0.50) 에서유의한차이가관찰되지않았다 [25]. 따라서중등도의 (intermediate) 좌주간부협착에서 FFR의측정은높은생존율과낮은사건발생을뒷받침하면서중재술을연기할수있는좋은근거자료가된다. 해부학적측면에서볼때 FFR은좌주간부관상동맥질환중특히개구부나체부병변의허혈평가를위해서반드시고려해야할사항이라고볼수있다. 최근중등도의협착을동반한좌주간부질환에서 FFR와 IVUS를비교한연구를보면혈관조영술의협착정도와 FFR의수치는일치도가매우부족했으며, 조영술상 50% 이상의협착이 FFR 0.80 이하를예측할민감도는 51%, 특이도는 75% 에불과하여중등도의협착이동반된환자에서는반드시 FFR의측정에따른치료계획이필요할것으로판단된다 [26]. 혈관조영술을통한좌주간부협착정도의평가는여러원인으로인하여부정확한경우가많았으며, 혈관내초음파 (intravascular ultrasound, IVUS) 를이용하여좌주간부병변의기능적특징과임상적결과의관련성이나형태학적, 생리학적그리고장기적예후와의통합적해석에대한시도가계속되어왔다. 최근 FFR threshold 수치를바탕으로의미있는좌주간부병변으로판정되었을때이에해당되는혈관내초음파의최소혈관내경 (minimal lumen area; MLA) 의한계점 (cut-point) 은 5.9 mm mm 2 으로다양하였으며, 의미있는좌주간부병변을정의할명확한한계점의정의에대해서는아직까지매우부족한실정이다. 최근 Kang 등의연구에의하면혈관조영술의협착정도에비하여 IVUS로측정한 MLA가더욱 FFR의변화를잘반영하였으며, FFR 0.80 이하를예측하는 IVUS-MLA 의예측수치는 4.8 mm 2 으로이때민감도 89%, 특이도 83%, 양성예측도 82%, 음성예측도 89%, 및정확도 86% 였다 [26]. 이연구는중등도의병변을보이는좌주간부병변에서 FFR을이용한생리학적의미를갖는 IVUS의적절한기준을제시한중요한연구로사료된다. 이는결론적으로좌주간부질환에서 FFR로대변되는관상동맥협착의기능적협착정도 (functional significance) 를혈관조영술상의협착정도보다 IVUS상의최소혈관내경이더욱더잘반영함을나타내는소견이다. IVUS 를기반으로한시술최적화일반적인관상동맥조영술은혈관내경을통한내경기록

4 - 대한내과학회지 : 제 81 권제 5 호통권제 615 호 (lumenogram) 에국한된정보만제공하기때문에병변이나경화반 (plaque) 의특성을파악하는데제약이있다. 특히좌주간부병변은큰혈관직경, 짧은정상참조부분 (short normal reference segment), 주요혈관과의겹침, 대동맥판막첨판으로인한혼탁화 (aortic cusp opacification), 조영제의유동성, 다양한각형성등의특성을보이기때문에혈관조영술만으로는병변의정확한파악에제한이따를수있다. 좌주간부병변에서중재시술동안, 특히말단분지부병변에서 IVUS 를통한중재술은협착의정도, 경화반특성, 해부학적구조 ( 특히주요분지의윤곽 ) 와함께, 정확한스텐트삽입을위한스텐트의적절한직경과길이선택및중재술후 stent underexpansion, 병변의적용범위의적절성여부, 잔여경화반, 스텐트의안착 (apposition) 여부등을확인하는데매우유용하게사용될수있다. 최근대규모다기관연구에서좌주간부질환중재시술시조영술만을이용한일반적인중재술과비교하여 IVUS를이용한중재술에서장기사망률을더낮출수있음이확인되었다 [27]. 또한제한적인결과이지만말단좌주간부병변에서약물방출스텐트중재술전후에 IVUS를통한정밀관찰이추후 adverse event를예측할수있음을시사하고있다. 특히좌주간부병변의개시부나체부의협착정도에비하여분지부병변의진단및치료에있어서 IVUS 소견을바탕으로한치료가매우중요할것으로판단된다. Kang 등은말단좌주간부병변의분지부에약물용출스텐트를삽입한 169명의환자를대상으로한연구에서, 좌주간부말단부터좌전하행지분지부 (LAD carina) 내에있는병변에서스텐스시술이후최소스텐트내면적 (minimal stent area) 을예측하는독립적인자로좌전하방동맥분기부의최소혈관내경 (β = 0.253, 95% CI = , p = 0.001) 과좌전하행지동맥과좌회선지가합류하는다각부 (polygon of confluence) 에서의최소혈관내경 (β = 0.205, 95% CI = , p = 0.008) 을제시하였다 [28]. 다변량 Cox 모델분석에의하면 3년내사건발생의독립적예측인자는여성 (adjusted HR = 2.56, 95% CI = , p = 0.018) 과다각부의최소혈관내경 (adjusted HR = 0.829, 95% CI = , p = 0.020) 으로나타났다. 즉, 좌전하행지에서 IVUS를 pullback 하는간단한방법을통해다각부의최소혈관내경을확인하는것이좌전주간지분지부의전반적인중증도와좌주간부말단분지부의스텐트후최소스텐트면 Figure 2. Minimal stent area (MSA) cutoff values for the prediction of angiographic in-stent restenosis (ISR) on a segmental basis. POC (polygon of confluence; polygon-shaped merging site of left anterior descending artery and left circumflex artery at distal left main portion). 적및추적기간동안장기적임상결과를예측할수있는중요한인자라할수있겠다. 최근 403명의보호되지않은좌주간부질환으로인하여스텐트시술을받은환자를대상으로재협착을예측할수있는부위별스텐트최소내경수치 (MSA) 가제시되었다 (Fig. 2) [29]. 이연구에의하면조영술상재협착을예측할수있는최소스텐트내경크기는좌주간부말단부 8.2 mm 2, POC 부위 7.2 mm 2, 좌전하행지기시부 6.3 mm 2, 좌회선지기시부 5.0 mm 2 으로이는좌주간부스텐트시술시장기재협착을예방하기위해시술최적화의최소수치로임상적의의가매우크다고할수있다. 좌주간부중재술이후발생한스텐트내협착 (in-stent restenosis) 의최적의치료방법 보호되지않은좌주간부병변에서스텐트내협착에대한임상경과나치료방법에대한자료는많지않다. FAILS (Failure in Left Main Study) 연구에서는좌전주간부병변에서스텐트이후재협착이발생한 70명의환자를대상으로한연구로써, 59명 (84.3%, DES, BMS, 또는풍선확장술을받은경우 ) 은재시술을받았고, 7명 (10%) 에서는우회수술을시행하였으며, 4명 (5.7%) 는약물적치료를받은환자가대상이되었다 [30]. 27개월간의추적관찰기간동안, 장기주요심장사건의누적발생률은약물적치료군에서 50% 에달하였으

5 - 박승정외 1 인. 좌주간부관상동맥시술의현재와미래 - 며, 재시술을받은군에서는 25%, 우회수술을받은군에서는 14% 의빈도를보이고있었다. Lee 등은좌주간부병변에서약물용출스텐트시술을받은 402명의환자중재협착이발생한 71명 (17.6%) 의환자를보고하였다 [31]. 이들중 57명은국소적재협착소견이었으며, 14명은미만성재협착을보이고있었다. 40명 (56.3%) 에서는재시술을받았으며, 10명 (14.1%) 은우회수술을그리고 21명 (29.6%) 은약물치료를받았다. 장기간의추적관찰기간동안 ( 중앙값 31.7개월 ) 발생한주요심장사건은약물치료군에서는 14.4%, 중재술을받은군에서는 13.6%, 우회수술을받은군에서는 10.0% 의분포를보이며통계학적으로유의한차이를보이지않았다. 이러한결과는좌주간부에서약물용출스텐트시술이후발생한스텐트내재협착의임상적장기경과가치료방법에상관없이비교적안정적인임상경과를보이는것을시사하며, 여러가지임상상황을바탕으로한시술자의선택에의하여재치료방법을선택하는것이바람직함을보여주고있다. 중재시술과우회수술간의효용성과안정성현재까지의치료가이드라인에의하면관상동맥우회수술이의미있는좌주간부질환에서재개통술방법으로추천되고있는표준치료법이다. 수술적접근방법은대동맥에서직접좌전하행지나좌회선지말단으로우회하기때문에좌주간부병변이갖는해부학적인난해성을쉽게극복할수있고, 또한다혈관질환의근치적재개통화 (complete revascularization) 를쉽게이룰수있다. 하지만이러한잇점에도불구하고, 수술후심근이전적으로정맥을통해혈류를공급받게되며, 정맥이식으로인해개통유지에제한이있다는점이간과할수없는단점으로알려져있다. 반면에큰혈관구경과접근하기쉬운점에서좌주간부병변에서의중재술은기술적으로용이하며, 성공적시술이이루어진다면기존의관상동맥혈관구조를유지하면서완전한동맥의재개통화 (arterial revascularization) 를보장할수있다는장점을가지고있다 [32]. 최근까지좌주간부질환에서관상동맥우회술과중재시술을비교한연구는표 1에요약되어있으며, 정리되어있으며연구의형태별로자세히정리하면다음과같다. Registry data 최근까지여러작은연구에서좌주간부병변에서관상동맥중재술과관상동맥우회술의중단기안전성과유용성에대한비교연구가있었다 [33-37]. 이들연구결과를보면, 관상동맥우회술을받는경우수술직후에심근경색이나 [33] 뇌혈관질환의발생이 [34] 스텐트시술에비하여유의하게증가하기때문에초기임상적사건의발생빈도는우회술보다조금높거나비슷하게나타났으며, 1년간의중단기사망률은양군간에유사하였다. 하지만목표병변재개통화의빈도는우회술에서보다중재술군에서지속적으로높게나타나고있었다. MAIN-COMPARE registry는대규모다기관환자모집을통하여보호되지않은좌주간부병변에서일반스텐트나약물용출스텐트를이용한스텐트시술과우회술의장기적경과를비교한연구이다 [19]. 국내유수의심장센터에서 2,240 명의보호되지않은좌주간부병변에서스텐트시술 ( 일반스텐트 ; 318명, 약물용출성스텐트 ; 784명 ) 및관상동맥우회술을받은환자 (1,138명) 가연구에참여하였다. 통계학적방법인 propensity-matching 후 3년째발표된결과를살펴보면, 사망위험도와사망, Q파심근경색, 뇌졸중등의위험도는중재술군과우회술군에서유사하게나타났으며, 일반스텐트나약물용출스텐트각각과우회술을비교한경우에도비슷한경향을보였다. 그러나목표병변재개통화의비율은우회술군에서보다중재술군에서의미있게높게나타났으며상대적위험도는스텐트종류에따른차이가있었으며, 우회술과비교하여약물용출스텐트에서는약 6배, 일반스텐트에서는 10배에가까운재개통화가필요하였다. 최근발표된 MAIN-COMPARE registry의 5년장기결과에서도 [38] 중재술군과우회수술군간에 5년째사망 (HR: 1.13; 95% CI: , p = 0.35) 이나사망, Q파심근경색, 뇌졸중의통합위험도 (HR: 1.07; 95% CI: , p = 0.59) 에서의미있는차이는없었다. 그러나목표병변재개통화의위험도는우회술의경우보다스텐트시술을받은경우에서높게나타났다 (HR: 5.11; 95% CI: , p = 0.001). 무작위임상시험연구좌주간부병변에서관상동맥우회술과중재술을무작위로비교한연구는극히제한적이다. 두가지치료법을무작

6 - The Korean Journal of Medicine: Vol. 81, No. 5,

7 - Seung-Jung Park, et al. Current status and future perspective of left main coronary intervention - 위배정으로통해혈관재개통화를시도한경우에라도, 종료점이너무복합적이거나, 대상환자수가너무작거나, 추적기간에제한이있는연구가대부분이었다. 또한연구에참여하는과정에서바이어스가발생할수있어연구가종료된이후주요제한점이될수있으나, 여러교란변수를배제한실제치료효과를평가할수있는유일한임상연구형태이다. 보호되지않은좌주간부병변에서관상동맥중재술과우회술을무작위배정으로비교한첫연구는 LeMANS trial이다. 이연구에서중재술은 52명의환자에서우회술은 53명의환자에서시행되었으며, 다혈관병변동반여부와상관없이좌주간부병변이있는환자들이었다 [39]. 관상동맥중재술군에서약물용출스텐트는 35% 에서사용되었으며, 우회술을받은경우 72% 에서좌내유동맥을이식하였다. 1년째일차연구종료점인좌심실박출률의절대적변화는우회술군보다중재술군에서유의하게높게나타났으나 (0.5 ± 0.8% vs. 3.3 ± 6.7%; p = 0.047), 이차연구종료점인생존율과주요뇌-심장주요사건의발생정도는두군에서비슷하게나타났다. 그러나이연구는환자수가적고비특이적인일차연구연구종료점을정함으로써임상적치료효과를적절히해석하는데많은제한점이있다. SYNTAX trial의좌주간부질환환자분석에서는 [40] 우회술을받은군과중재술을받은환자군에서 12개월동안주요심장또는뇌혈관사건이나, 사망, 심근경색, 뇌졸중이유사하게나타났으나, 목표혈관재개통화는약물용출스텐트를사용한군에서높게나타났다. 특히, 좌주간부병변이있는환자의세부분석에서좌주간부병변만있거나, 단일혈관병변만동반된경우에비해둘또는세가지혈관에동시에병변이동반되었던경우에서임상사건의발생이높은비율로나타났으며 (7.1% vs. 7.5% vs. 19.8% vs. 19.3%), 이러한경향은 3년간의장기임상경과관찰에서도지속되는소견이었다 [41]. 최근 Boudriot 등은보호되지않은좌주간부병변에서무작위로, sirolimus-용출스텐트를사용한경우와 (100명) 관상동맥우회술 (101명) 을받은경우의비교한결과를보고하였다 [42]. 12개월째비열등검정을통한일차연구종결점은중재술군에서우회술군과비교하여열등하지않은결과를보여주었으며 (19.0% vs. 13.9%), 사망과심근경색을통합한발생률에서도비슷한결과를보였다 (5.0% vs. 7.9%). 하지만재개통술의발생률은중재술군에서유의하게높게나타났다 (14.0% vs. 5.9%). 최근좌주간부치료로관상동맥우회술과 sirolimus- 용출스텐트를이용한관상동맥중재술을무작위로배정한대규모연구의하나인 PRECOMBAT (Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease) 의결과가발표되었다 [43]. 치료방법에따라각각 300명씩의환자가연구에참여하였으며, 일차연구종결점은주요심장사건또는뇌혈관사건으로사망, 심근경색, 뇌졸중, 목표혈관재개통화등을포함하고있으며, 2년째일차종결점의발생률은양군간에통계학적으로유의한차이가없었다 ( 스텐트시술, 12.1% vs. 우회술, 8.1%, p = 0.12). 또한사망, 심근경색, 뇌졸중의통합발생률또한양군에서유사하였다 (4.4% vs. 4.7%). 하지만혈관재개통술은중재술군에서유의하게높게발생하였다 (9.0% vs. 4.2%; p = 0.02). 앞으로발표될대규모무작위임상연구인 EXCEL (Evaluation of Xience Prime versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) 연구또한약물용출스텐트 ( 에버로리무스용출성스텐트 ) 를이용한중재술과관상동맥우회술의효용성과안정성을비교할연구로써좌주간부병변에서우회술과중재술의위치를재조명할것으로여겨져귀추가주목된다. 메타분석 (meta-analysis) Taggart 등이발표한통합분석 (systemic analysis) 에의하면초기 ( 병원입원중사망또는 30일이내 ) 사망률이나, 장기사망률 (1-2년이내 ) 이우회술과비교하여일반스텐트를사용한경우 ( 초기 0-14%, 평균 6%; 후기 3-31%, 평균 17%) 나, 약물용출스텐트를사용한경우 ( 초기 0-10%, 평균 2%; 후기 0-14%, 평균 7%) 에서높게나타남을발표하였다 [44]. 이와다른연구결과로 Takagi 등은보호되지않은좌주간부병변이있는 2,181명의환자 ( 중재술 1,006명, 우회술 1,175 명 ) 의 6개연구 ( 무작위연구 1개, 관찰연구 5개 ) 를메타분석하였다 [45]. 이연구에서두군간에사망률에는유의한차이를보이지않았으나 (OR 0.99, 95% CI , p = 0.97), 중재술군에서재개통화가유의하게높게나타났다 (OR 5.05, 95% CI , p < 0.001). Lee 등도최근보호되지않은좌주간부병변에서약물용출스텐트중재술과우회술을비교한비슷한메타분석을

8 - 대한내과학회지 : 제 81 권제 5 호통권제 615 호 발표하였으며 [46], 8개의임상연구 ( 무작위연구 2, 관찰연구 6) 에서 2,905명의환자가분석되었는데, 1년의추적기간동안사망률 (OR 1.12, 95% CI ) 이나사망, 심근경색, 뇌졸중의통합발생률 (OR 1.25, 95% CI ) 은두군간에유의한차이가없었다. 하지만목표혈관재개통화의비율은중재술군에비해우회술군에서유의하게낮게나타났다 (OR 0.44, 95% CI ). 그러나이와같은전반적분석이나, 메타분석은환자수의제한이나선택바이어스또는검토되는과정에서출판바이어스가있을수있어그해석에있어주의를요하는예비결과임을알아야하며, 임상연구를포함하고있어내적타당성을온전히신뢰하는것은옳지않다. 장기적임상결과들좌주간부병변에서우회술과비교하여관상동맥중재술의성공적인이용에대한여러연구가보고되었으나 5-10년까지의장기적인비교결과에대해서는아직제한적이다. 다른부위의관상동맥질환에서관상동맥스텐트삽입술이 5-10년동안안정적이라하더라도보호되지않은좌주간부병변에서스텐스시술의적용에대해서는아직확립된바가없다. ASAN- MAIN (ASAN Medical Center-Left MAIN Revascularization) registry는우회술과중재술을가장장기간비교한연구결과로써일반스텐트는 10년간약물용출스텐트는 5년간추적 관찰되었다 [45]. 우회술과비교하여일반스텐트중재술을받은 10년코호트군에서보정후의사망위험도 (HR: 0.81; 95% CI: 0.44 to 1.50; p = 0.50) 와사망, Q파심근경색, 뇌졸중의통합발생위험도 (HR: 0.92; 95% CI: 0.55 to 1.53; p = 0.74) 는두군간에유의한차이를보이지않았다. 다만, 목표혈관재개통의위험도는유의하게일반스텐트중재술을시행받은군에서높게나타났다 (HR: 10.34; 95% CI: 4.61 to 23.18; p = 0.001). 약물용출스텐트시술을받은 5년추적코호트군과우회술을받은환자의비교에서도보정후사망위험도 (HR: 0.83; 95% CI: 0.34 to 2.07; p = 0.70) 와사망등의통합발생률의위험도 (HR: 0.91; 95% CI: 0.45 to 1.83; p = 0.79) 는여전히유의한차이가없었으나, 목표혈관재개통률의위험도 (HR: 6.22; 95% CI: 2.26 to 17.14; p = 0.001) 는중재술군에서높게나타났다. 미국심장협회 / 미국심장학회의현재의가이드라인의변화미국심장협회 / 미국심장학회에서관상동맥중재술에대한가이드라인이최근개정되었다. 스텐트시술에대해 off-label 경험과임상연구 ( 특히 SYNTAX 연구및 MAINCOMPARE 연구 ) 의증가를반영하여치료가이드라인을개정하고자하고있으며, 좌주간부협착의지침으로중재술치료를 Class IIb로승격시키고자하고있다 [47]. 현재의축적된지식 Table 2. Changes of the ACC/AHA and ESC Guideline for PCI for Unprotected Left Main Coronary Artery Disease Guideline Past recommendation Current recommendation ACC/AHA Guidelines 2005 PCI Guideline Class III 2009 PCI Guideline Class IIb ; PCI is not recommended in patients with left main disease ; PCI of the left main coronary artery with stents as an and eligibility for CABG (Level of Evidence: C). alternative to CABG may be considered in patients with anatomic conditions that are associated with a low risk of PCI procedural complications and clinical conditions that predict an increased risk of adverse surgical outcomes (Level of Evidence: B). ESC Guidelines 2005 PCI Guideline Class IIb C 2010 PCI Guideline Class IIa B-III B ; stenting for unprotected LM disease should only be ; Left main (isolated or 1VD, ostium/shaft)-iia B considered in the absence of other revascularization options ; Left main (isolated or 1VD, distal bifurcation)-iib B ; Left main + 2VD or 3VD, SYNTAX score 32-IIb B ; Left main + 2VD or 3VD, SYNTAX score >33-III B

9 - 박승정외 1 인. 좌주간부관상동맥시술의현재와미래 - 과향후의연구를기반으로한다면, 좌주간부병변에서스텐트중재술을 IIb보다는 IIa으로여기는것이타당할것으로여겨지며이에대한추가적인논의가있을것으로예상된다. 최근유럽심장학회와유럽심장- 흉부학회에서도좌주간부병변에서으로관상동맥우회술을대신할만한치료법으로관상동맥중재술을적용할진료지침을발표하였는데정리하면다음과같다 ; (1) 좌주간부단일병변이거나단일혈관병변이면서개구부인경우 (class IIa B), (2) 좌주간부단일병변이거나단일혈관병변이면서말단분지부인경우 (class IIb B), (3) 2 또는 3혈관병변이동반된좌주간부협착이면서 SYNTAX score 가 32이하인경우 (class IIb B), (4) 2 또는 3혈관병변이동반된좌주간부협착이면서 SYNTAX score 가 33 이상인경우 (class III B) 이다 [47]. 표 2는최근까지의미국및유럽의좌주간부질환치료에대한과거및현재의가이드라인을정리한내용이다. 결론 : 좌주간부스텐트시술의현재와미래 최근까지의임상연구와대규모 off-label의경험들을바탕으로좌주간부관상동맥질환에서스텐트를이용한관상동맥중재술이기존의표준치료방법인관상동맥우회술과비교하여사망률과이환율에서긍정적인결과를보여주고있어우회술을대치할만한치료로각광받고있다. 또한최근발표된다기관무작위임상연구인 PRECOMBAT 연구의결과가발표되면서좌주간부병변에서약물스텐트를이용한시술방법이더욱더확고한입지를다지게되었다. 향후머지않은미래에더욱정교한기술과기구의발전및생리학적, 영상학적보조와더불어우수한약제의병합으로관상동맥중재술은좌주간부병변에서향상된성공률과장기임상안정성을증명함으로써그위상을더욱확고히할것으로예상된다. 중심단어 : 관상동맥우회술 ; 관상동맥중재술 ; 좌주간부병변 REFERENCES 1. Chaitman BR, Fisher LD, Bourassa MG, et al. Effect of coronary bypass surgery on survival patterns in subsets of patients with left main coronary artery disease: report of the Collaborative Study in Coronary Artery Surgery (CASS). Am J Cardiol 1981;48: Takaro T, Peduzzi P, Detre KM, et al. Survival in subgroups of patients with left main coronary artery disease: Veterans Administration Cooperative Study of Surgery for Coronary Arterial Occlusive Disease. Circulation 1982;66: Park SJ, Park DW. Percutaneous coronary intervention with stent implantation versus coronary artery bypass surgery for treatment of left main coronary artery disease: is it time to change guidelines? Circ Cardiovasc Interv 2009;2: 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: Valgimigli M, van Mieghem CA, Ong AT, et al. Short- and long-term clinical outcome after drug-eluting stent implantation for the percutaneous treatment of left main coronary artery disease: insights from the Rapamycin-Eluting and Taxus Stent Evaluated at Rotterdam Cardiology Hospital registries (RESEARCH and T-SEARCH). Circulation 2005;111: Chieffo A, Stankovic G, Bonizzoni E, et al. Early and mid-term results of drug-eluting stent implantation in unprotected left main. Circulation 2005;111: Hsueh SK, Wu CJ, Fang HY, et al. Comparison of drug-eluting stent with bare metal stent for distal de novo unprotected left main coronary artery stenosis: a propensity score-matched cohort study. Circ J 2011;75: Pandya SB, Kim YH, Meyers SN, et al. Drug-eluting versus bare-metal stents in unprotected left main coronary artery stenosis a meta-analysis. JACC Cardiovasc Interv 2010;3: Chieffo A, Park SJ, Valgimigli M, et al. Favorable long-term outcome after drug-eluting stent implantation in nonbifurcation lesions that involve unprotected left main coronary artery: a multicenter registry. Circulation 2007;116: Kim YH, Park SW, Hong MK, et al. Comparison of simple and complex stenting techniques in the treatment of unprotected left main coronary artery bifurcation stenosis. Am J Cardiol 2006; 97: Valgimigli M, Malagutti P, Rodriguez Granillo GA, et al. Single-vessel versus bifurcation stenting for the treatment of distal left main coronary artery disease in the drug-eluting stenting era: clinical and angiographic insights into the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) and Taxus-Stent Evaluated at Rotterdam Cardiology Hospital (T-SEARCH) registries. Am Heart J 2006;152: Palmerini T, Sangiorgi D, Marzocchi A, et al. Ostial and midshaft lesions vs. bifurcation lesions in 1111 patients with unprotected left main coronary artery stenosis treated with drug-eluting stents: results of the survey from the Italian Society of Invasive Cardiology. Eur Heart J 2009;30: Lagerqvist B, James SK, Stenestrand U, Lindback J, Nilsson T, Wallentin L; SCAAR Study Group. Long-term outcomes with

10 - The Korean Journal of Medicine: Vol. 81, No. 5, drug-eluting stents versus bare-metal stents in Sweden. N Engl J Med 2007;356: Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med 2007;356: Mauri L, Hsieh WH, Massaro JM, Ho KKL, D'Agostino R, Cutlip DE. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med 2007;356: Chieffo A, Park SJ, Meliga E, et al. Late and very late stent thrombosis following drug-eluting stent implantation in unprotected left main coronary artery: a multicentre registry. Eur Heart J 2008;29: Meliga E, Garcia-Garcia HM, Valgimigli M, et al. Longest available clinical outcomes after drug-eluting stent implantation for unprotected left main coronary artery disease: the DELFT (Drug Eluting stent for LeFT main) Registry. J Am Coll Cardiol 2008;51: Mehilli J, Kastrati A, Byrne RA, et al. Paclitaxel-versus sirolimuseluting stents for unprotected left main coronary artery disease. J Am Coll Cardiol 2009;53: Seung KB, Park DW, Kim YH, et al. Stents versus coronary-artery bypass grafting for left main coronary artery disease. N Engl J Med 2008;358: 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: Stone GW, Rizvi A, Newman W, et al. Everolimus-eluting versus paclitaxel-eluting stents in coronary artery disease. N Engl J Med 2010;362: Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360: Jasti V, Ivan E, Yalamanchili V, Wongpraparut N, Leesar MA. Correlations between fractional flow reserve and intravascular ultrasound in patients with an ambiguous left main coronary artery stenosis. Circulation 2004;110: Courtis J, Rodés-Cabau J, Larose E, et al. Usefulness of coronary fractional flow reserve measurements in guiding clinical decisions in intermediate or equivocal left main coronary stenoses. Am J Cardiol 2009;103: Hamilos M, Muller O, Cuisset T, et al. Long-term clinical outcome after fractional flow reserve-guided treatment in patients with angiographically equivocal left main coronary artery stenosis. Circulation 2009;120: Kang SJ, Lee JY, Ahn JM, et al. Intravascular ultrasound-derived predictors for fractional flow reserve in intermediate left main disease. JACC: Cardiovacular Interventions. 2011;In Press. 27. Park SJ, Kim YH, Park DW, et al. Impact of intravascular ultrasound guidance on long-term mortality in stenting for unprotected left main coronary artery stenosis. Circ Cardiovasc Interv 2009;2: Kang SJ, Mintz GS, Kim WJ, et al. Effect of intravascular ultrasound findings on long-term repeat revascularization in patients undergoing drug-eluting stent implantation for severe unprotected left main bifurcation narrowing. Am J Cardiol 2011; 107: Kang SJ, Ahn JM, Song HG, et al. Comprehensive intravascular ultrasound assessment of stent area and its impact on restenosis and adverse cardiac events in 403 patients with unprotected left main disease. Circ Cardiovasc Interv Sheiban I, Sillano D, Biondi-Zoccai G, et al. Incidence and management of restenosis after treatment of unprotected left main disease with drug-eluting stents 70 restenotic cases from a cohort of 718 patients: FAILS (Failure in Left Main Study). J Am Coll Cardiol 2009;54: Lee JY, Park DW, Kim YH, et al. Incidence, predictors, treatment, and long-term prognosis of patients with restenosis after drug-eluting stent implantation for unprotected left main coronary artery disease. J Am Coll Cardiol 2011;57: Takagi H, Umemoto T. Drug-eluting stents vs bypass surgery for unprotected left main disease. Circ J 2010;74: Chieffo A, Morici N, Maisano F, et al. Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience. Circulation 2006;113: Lee MS, Kapoor N, Jamal F, et al. Comparison of coronary artery bypass surgery with percutaneous coronary intervention with drug-eluting stents for unprotected left main coronary artery disease. J Am Coll Cardiol 2006;47: Palmerini T, Marzocchi A, Marrozzini C, et al. Comparison between coronary angioplasty and coronary artery bypass surgery for the treatment of unprotected left main coronary artery stenosis (the Bologna Registry). Am J Cardiol 2006;98: Sanmartín M, Baz JA, Claro R, et al. Comparison of drug-eluting stents versus surgery for unprotected left main coronary artery disease. Am J Cardiol 2007;100: Cheng CI, Lee FY, Chang JP, et al. Long-term outcomes of intervention for unprotected left main coronary artery stenosis: coronary stenting vs coronary artery bypass grafting. Circ J 2009;73: Park DW, Seung KB, Kim YH, et al. Long-term safety and efficacy of stenting versus coronary artery bypass grafting for unprotected left main coronary artery disease: 5-year results from the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry. J Am Coll Cardiol 2010;56: Buszman PE, Kiesz SR, Bochenek A, et al. Acute and late outcomes of unprotected left main stenting in comparison with

11 - Seung-Jung Park, et al. Current status and future perspective of left main coronary intervention - surgical revascularization. J Am Coll Cardiol 2008;51: Morice MC, Serruys PW, Kappetein AP, et al. Outcomes in patients with de novo left main disease treated with either percutaneous coronary intervention using paclitaxel-eluting stents or coronary artery bypass graft treatment in the Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) trial. Circulation 2010;121: Serruys PW. The synergy between percutaneous coronary intervention with TAXUS and Cardiac Surgery (SYNTAX) Study: the 3-year outcomes of the SYNTAX trial in the subset of patients with left main disease. Transcatheter Cardiovascular Therapeutics Boudriot E, Thiele H, Walther T, et al. Randomized comparison of percutaneous coronary intervention with sirolimus-eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis. J Am Coll Cardiol 2011;57: Park SJ, Kim YH, Park DW, et al. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med 2011;364: Taggart DP, Kaul S, Boden WE, et al. Revascularization for unprotected left main stem coronary artery stenosis stenting or surgery. J Am Coll Cardiol 2008;51: Takagi H, Kawai N, Umemoto T. Stenting versus coronary artery bypass grafting for unprotected left main coronary artery disease: a meta-analysis of comparative studies. J Thorac Cardiovasc Surg 2009;137:e54-e Lee MS, Yang T, Dhoot J, Liao H. Meta-analysis of clinical studies comparing coronary artery bypass grafting with percutaneous coronary intervention and drug-eluting stents in patients with unprotected left main coronary artery narrowings. Am J Cardiol 2010;105: Kushner FG, Hand M, Smith SC Jr, et al focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2009;120: