ISCHEMIC HEART DISEASE (S BRENER, SECTION EDITOR)

Revascularization for Left Main and Multivessel CoronaryArtery Disease in the Drug-Eluting Stent Era: Integrationof Recent Drug-Eluting Stent Trials

Samip Vasaiwala & David O. Williams

Published online: 26 May 2012# Springer Science+Business Media, LLC 2012

Abstract As older patients comprise a greater proportion ofthe population, the incidence of multivessel and left maincoronary artery disease is increasing. Given the improve-ments in percutaneous coronary intervention, more patientsare suitable for this revascularization strategy. However, theoptimal revascularization strategy remains a moving target.Numerous trials, extending from the bypass surgery versusmedical therapy era to the most current drug-eluting stentversus bypass surgery era, provide information to select themost appropriate revascularization strategy. The objective ofthis review is to summarize these data.

Keywords Multivessel coronary artery disease . Left maincoronary artery disease . Drug-eluting stents .

Revascularization . Multivessel coronary artery disease

Introduction

Rapid progress in the medical and procedural treatmentoptions for coronary artery disease (CAD), culminatingmost recently with the introduction of drug-eluting stents

(DES), has been synchronous with the increasing prevalenceof complex CAD in the aging US population [1]. Thegeneral approach to CAD management begins with thepresentation, ranging from no overt manifestations (asymp-tomatic CAD) to cardiogenic shock. While all agree thatbenefit of revascularization is greatest for the most severemanifestations of CAD, which type of revascularization toemploy remains a matter of frequent debate. Whether revas-cularization should be pursued and which strategy is best iseven more contentious at the more stable end of the CADcontinuum.

For the purpose of this review, we focus on a specificpatient population, those individuals with left main (LM)and/or multivessel CAD (MV-CAD), with particular atten-tion placed on recent DES trials. MV-CAD not involving theLM and LM-CAD will be discussed separately with theunderstanding that significant overlap between the twoexists. Also, LM-CAD refers to unprotected left main(UPLM) lesions only (ie, those without a bypass graft inthe left anterior descending (LAD) or left circumflex arterialterritories). For the sake of clarity, “MV-CAD” will refer toMV disease without concomitant LM disease unless statedotherwise.

Multivessel CAD

The last 40 years of CAD management can be convenientlyseparated into discrete eras. The first era extends from 1964with the introduction of coronary artery bypass graft surgery(CABG) to 1977, when Andreas Gruentzig performed thefirst percutaneous transluminal coronary angioplasty(PTCA) in Zurich, Switzerland. This nonsurgical form ofcoronary revascularization was followed by a series of land-mark trials comparing PTCAwith CABG, which at that time

S. Vasaiwala :D. O. WilliamsBrigham and Women’s Hospital,Boston, MA, USAe-mail: svasaiwala@partners.org

S. Vasaiwala1620 Tremont Street, Clinical Biometrics, 3rd Floor,One Brigham Circle,Boston, MA 02120, USA

D. O. Williams (*)1620 Tremont Street, BC-3-PF-30,Boston, MA 02120, USAe-mail: dowilliams@partners.org

Curr Cardiol Rep (2012) 14:468–476DOI 10.1007/s11886-012-0274-x

was, and still remains, the standard of revascularization forMV-CAD.

The second era, that of PTCA, ended with the introduc-tion of bare-metal stents (BMS) in 1986, followed by an-other wave of randomized clinical trials comparing BMSwith CABG for the treatment of MV-CAD. The use of BMSreduced the risk of abrupt vessel closure and lesion recur-rence (restenosis) compared with PTCA [2, 3]. However,initial enthusiasm was tempered by the development of in-stent restenosis (ISR), for which there was no consistentlyeffective therapy [4]. DES were introduced to address thisissue of ISR due to neointimal hyperplasia, ushering in thecurrent era of stent technology. The focus of this review ison the “DES Era”; however, a brief discussion of whatpreceded DES use is included to add perspective.

When Is Revascularization for Multivessel CAD Indicatedand Which Strategy Is Best?

The intent of revascularization in stable CAD is to relievesymptoms when medical therapy is inadequate. On the otherhand, when medical therapy is successful (ie, symptoms areabsent or minimal), indications for revascularization are un-clear even when objective evidence of ischemia is present. Inunstable CAD (acute coronary syndromes), benefit from re-vascularization in regard to clinical outcomes is well accepted.According to the American Heart Association (AHA)/Amer-ican College of Cardiology (ACC) guidelines [5] for MV-CAD, CABG is preferred over percutaneous coronary inter-vention (PCI - Class I) in patients with three-vessel disease,especially when the left ventricular ejection fraction (LVEF) isless than 50 %. CABG is also preferred in patients with two-vessel disease with significant proximal LAD CAD and eitherLVEF less than 50 % or demonstrable ischemia on noninva-sive testing, as mortality benefit has been demonstrated com-pared withmedical therapy alone. PCI is acceptable in patientswith two- or three-vessel disease with significant proximalLAD CAD who have anatomy amenable to PCI and a normalLVEF without the presence of diabetes (Class I). PCI orCABG is recommended for patients with two-vessel diseasewithout significant proximal LAD CAD but with a large areaof viable myocardium and high-risk findings on noninvasivetesting (Class I). Survival benefit with revascularization in thissetting is unclear. The ISCHEMIA (International Study Com-paring Health Effectiveness with Medical and InvasiveApproaches) trial, which will randomize patients with moder-ate to severe ischemia detected on noninvasive evaluation toeither optimal medical therapy (OMT) alone versus diagnosticangiogram and revascularization as indicated plus OMT, willaddress this link between mortality and ischemia in the ab-sence of severe CAD.

Approach to patients with stable CAD (OMT vs PCI) wasstudied in the COURAGE (Clinical Outcomes Utilization

Revascularization and Aggressive Drug Evaluation) trial [6].COURAGE was a randomized trial involving 2287 patientswho had objective evidence of myocardial ischemia and sig-nificant CAD, without LM involvement. A total of 1149patients were assigned to PCI with OMT (PCI group) and1138 to OMT alone (OMT group) following coronary angi-ography. Sixty-nine percent of patients had two- or three-vessel disease in both the PCI and medical therapy groups.Thirty-one percent of patients had proximal LAD CAD in thePCI group compared with 37 % in the medical therapy group(P00.01). Over a median follow-up of 4.6 years, there was nodifference in the cumulative rate of death, myocardial infarc-tion (MI), and stroke between the two groups (20.0 % PCI vs19.5 % OMT; hazard ratio [HR] 1.05, 95 % CI: 0.87–1.25,P00.62). Although no mortality reduction was detected in theoverall trial, in a 314 patient substudy evaluating the extent ofischemia before and after PCI via myocardial perfusion imag-ing, patients undergoing PCI exhibited significant ischemiareduction (33 % vs 19 %; P00.0004) compared to thosetreated with medical therapy. Moreover, patients with ische-mia reduction and baseline moderate to severe ischemia had alower unadjusted rate of death or MI compared to patientswithout ischemia reduction (P00.001 [risk-adjustedP00.08]). These findings, although provocative, were notconclusive. The planned ISCHEMIA trial is designed to ad-dress this question.

When evaluating any patient with CAD, the basic frame-work surrounding revascularization involves two primaryquestions: when revascularization is indicated and how itshould be performed. While the COURAGE trial shed somelight on the first question, it had little to do with the lattergiven that all patients in the trial undergoing revasculariza-tion received PCI by design. However, each of the revascu-larization eras is defined by key clinical trials designed toanswer this question.

CABG Versus PTCA for Multivessel CAD

The introduction of PTCA resulted in several clinical trialsdesigned to answer whether the mortality and symptomrelief accomplished by CABG can be achieved nonsurgi-cally via PTCA without the associated comorbidity of theCABG procedure [7–13].

BARI (Bypass Angioplasty Revascularization Investiga-tion), which was the largest of the CABG versus PTCAtrials, enrolled 1829 symptomatic patients with two- orthree-vessel disease and without LM involvement. Five-,seven-, and 10-year follow-up have been published[14–16], all showing no difference in survival between theCABG and PTCA arms at 10 years. However, the subset ofpatients with diabetes had a significant 10-year survivalbenefit with CABG compared to PTCA (57.9 % vs45.5 %, P00.025). Patients who did not consent to

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randomization (N02010) were treated according to physi-cian preference and followed in the BARI registry [17]. Ofnote, no survival difference was detected with CABG com-pared with PTCA in both the diabetic and nondiabetic sub-sets within the registry population. Similarly, a smallersingle-center randomized study comparing medical therapy,PTCA, and CABG showed no significant difference inmortality at 10-year follow-up [18].

CABG Versus BMS for Multivessel CAD

The introduction of BMS led to renewed enthusiasm for PCIgiven the dramatically reduced rates of abrupt vessel closureand restenosis compared to PTCA alone. Similar to the priorera, there were a series of randomized trials evaluating theefficacy and safety of BMS compared with CABG for MV-CAD [18–24, 25••]. Despite lower rates of restenosis andtarget vessel revascularization (TVR) compared with PTCA,the rates of repeat revascularization remained significantlyhigher in the BMS groups compared to those treated withCABG. Again, no difference in mortality was detectedbetween the two groups over long-term follow-up.

CABG Versus DES for Multivessel CAD

The approval of DES resulted in head-to-head DES versusCABG comparative trials and registries, some of which arestill ongoing.

ARTS (Arterial Revascularization Therapy Study) II wasa registry comparing outcomes with sirolimus-eluting stents(SES) in 607 patients with MV-CAD undergoing stentingwith SES compared with a historical control comprised ofthe patients in the ARTS I trial treated with CABG (605) orBMS (600) [26]. The primary end point of the study was acomposite of all-cause death, MI, cerebrovascular event, orany repeat revascularization. At 5-year follow-up, the pri-mary end point occurred more frequently in the DES groupcompared with the CABG group from ARTS I (27.5 % vs21.1 %, P00.02) and less frequently than in the BMS group(27.5 % vs 41.5 %, P<0.001).

An observational analysis from the New York state PCIand CABG registry reported 18-month follow-up onpatients undergoing revascularization for MV-CAD withDES versus CABG [27]. For patients with three-vesselCAD, the adjusted HR for mortality was 0.80 (CABG vsPCI, 95 % CI, 0.65–0.97; P00.03) and among patients withtwo-vessel disease the adjusted HR for mortality was 0.71(CABG vs PCI; 95 % CI, 0.57–0.89; P00.003). Interesting-ly, no significant differences in mortality were detectedamong the higher-risk subgroups (patients with diabetes,those with LVEF <40 %, and patients >80 years of age).

Three randomized trials evaluating the effectiveness ofDES versus CABG forMV-CAD to date have been published:

SYNTAX (Synergy Between Percutaneous Coronary Inter-vention with Taxus and Cardiac Surgery) trial [28••], CARDia(Coronary Artery Revascularization in Diabetes) trial [29•],and the BARI 2D (Bypass Angioplasty RevascularizationInvestigation in Type 2 Diabetics Trial) [30]. The latter twotrials focused on the patients with diabetes and MV-CAD andare discussed separately below. SYNTAX was a multicentertrial involving 1800 patients with three-vessel or LM-CADrandomized in a 1:1 fashion to PCI or CABG. The noninfer-iority primary end point was a composite of all-cause death,stroke, MI, or repeat revascularization over 12-month follow-up. The primary end point occurred more often in the PCI arm(17.8 % vs 12.4 %, respectively, P00.002), and was drivenprimarily by higher repeat revascularization rates in the PCIarm (13.5 % vs 5.9 %, P<0.001). The end points of death, MI,and stroke were comparable between the two arms (7.6 % PCIvs 7.7 % CABG; HR 1.00 [95 % CI, 0.72, 1.38], P00.98);however, CABG was associated with a significantly greaterhazard of stroke (2.2 % vs 0.6 %, P00.003). At 3-year follow-up, the repeat revascularization rate continued to be higher forPCI (19.7 % vs 10.7 %, respectively, P<0.001) [31]. As seenat 1-year follow-up, major adverse cardiovascular and cere-brovascular events (MACCE) rates were not different be-tween the two arms (14.1 % PCI vs 12.0 % CABG, P00.21). At 3 years, the stroke rate difference was significantlydifferent (2.0 % PCI vs 3.4 % CABG, P00.07); however, MIwas higher in the PCI arm (7.1 % vs 3.6 %, P00.002). The 4-year cumulative results of SYNTAX demonstrated no signif-icant difference in the combine death/stroke/MI end point(18 % PCI vs 14.6 % CABG, P00.07); however, MACCEwas higher with PCI (33.5 % PCI vs 23.6 % CABG, P<0.001). This difference in MACCE was largely due to a largedifference in repeat revascularization procedures with PCI(23 % PCI vs 11.9 % CABG, P<0.001) [32].

In the SYNTAX trial, coronary angiograms were evalu-ated according to a unique scoring algorithm and classifiedinto low (0–22), intermediate (23–32), and high (> 32)scores based on the level of CAD complexity [33]. At 1-year follow-up, there was no difference in the primary endpoint among patients with low (13.6 % PCI vs 14.7 %CABG, P00.71) or intermediate (16.7 % PCI vs 12.0 %CABG, P00.10) scores. Patients with high SYNTAX scoreshad a significantly higher primary end point rate in the PCIarm (23.4 % vs 10.9 %, respectively, P<0.001).

At 3-year follow-up, the difference in the primary endpoint rate remained nonsignificant among patients with lowSYNTAX scores [31]. In patients with intermediate scores,the curves representing the primary end point rate continuedto separate and the difference was significant at 3-yearfollow-up (27.4 % PCI vs 18.9 % CABG, P00.02). At 4-year follow-up, no significant difference in the composite ofdeath/stroke/MI was detected among patients with interme-diate SYNTAX scores. However, among patients with high

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scores, there was a statistically significant difference in thisend point between the treatment arms (22.7 % PCI vs14.6 % CABG, P00.01) [32]. These data provide supportfor the use of DES in selected patients with MV-CAD.

Multivessel Revascularization in Patients with Diabetes

Diabetes constitutes a major risk factor for the development andprognosis of CAD and warrants a separate discussion. Patientswith diabetes are more likely to present with MV-CAD thanpatients without diabetes and make up 25% to 30% of patientsundergoing revascularization for CAD [16]. Several observa-tional studies and a few randomized trials have addressed thequestion of which revascularization strategy is best for thediabetes subset and these data are discussed here.

PTCA Versus CABG for Patients with Diabetesand Multivessel CAD

BARI was the first trial to distinguish diabetes as an inde-pendent predictor of worse outcomes in patients with MV-CAD. The subset of patients with diabetes within BARI hada significantly higher survival rate with CABG compared toPCI at 5.4 years (81 % vs 66 %, P00.003) [14], 7 years(76 % vs 56 %, P00.001)(15), and 10 years (58 % vs 46 %,P00.025) [16].

A meta-analysis of patients with diabetes from the BARI,EAST (Emory Angioplasty Versus Surgery Trial), CABRI(Coronary Angioplasty Versus Bypass RevascularizationInvestigation), and RITA (Randomized Intervention Treat-ment of Angina) trials reported significantly lower all-causemortality with CABG compared to PTCA at 4 years (abso-lute risk difference 8.6 %; 95 % CI: 2.2 % to 15 %, P<0.01)but not at 6.5 years (absolute risk difference 3.9 %; 95 % CI:-17 % to 25 %, P00.71) [34].

BMS Versus CABG for Patients with Diabetesand Multivessel CAD

In the ARTS I trial, the 5-year mortality in patients withdiabetes did not differ between the BMS and CABG arms(BMS 13.4 % vs CABG 8.3 %; RR 1.61 [95 % CI, 0.71,3.62], P00.27); however, the overall event rate was higher inthe BMS arm for patients diabetes and MV-CAD secondary tohigher rates of repeat revascularization in the BMS arm (42.9%vs 10.4 %; RR 4.11, 95 % CI: 2.20–7.68, P<0.001) [22].

DES Versus CABG for Patients with Diabetesand Multivessel CAD

Randomized trials and observational studies among patientswith diabetes undergoing revascularization with DES versus

BMS have consistently shown lower rates of repeat proce-dures with DES [35–40].

To date, two randomized studies have compared PCI withDES to CABG in patients with diabetes: SYNTAX and CAR-Dia. SYNTAX was not a dedicated diabetes revascularizationtrial, but did include a substantial proportion of patients withdiabetes. CARDia was a randomized trial of 510 patients withdiabetes andMV-CAD undergoing CABG or PCI; 70% in thePCI arm received DES [29•]. The composite end point ofdeath, MI, and stroke was not different between the two arms(11.6% PCI vs 10.2%CABG;HR 1.15 [95%CI 0.65, 2.03]).CABG was associated with a lower rate of TVR (9.9 % vs2 %, P00.001). In the SYNTAX trial, there was no differencein all-cause mortality at 1 year between the DES versusCABG arms among patients with diabetes (8.4 % PCI vs6.4 % CABG, P00.43). Consistent with the overall studycohort, CABG was associated with a significant reduction inrepeat revascularization (20.3 % vs 6.4 %, P<0.001) [41].Patients with complex coronary anatomy (SYNTAX score>32) had lower all-cause mortality with CABG compared toPCI (13.5 % vs 4.1 %, P00.04). These studies were limiteddue to the small sample size of patients with diabetes enrolledin both studies. The effectiveness of DES versus CABG iscurrently being studied in a larger cohort of 2500 patients withdiabetes enrolled in the National Heart, Lung, and BloodInstitute (NHLBI)–sponsored FREEDOM (Future Revascu-larization Evaluation in Patients with Diabetes Mellitus: Op-timal Management of Multivessel Disease) trial [42].

BARI 2D was a trial designed to test the hypothesis thatprompt revascularization (with either PCI or CABG) inpatients with diabetes and MV-CAD would be associatedwith reduced hazard of death or the composite of death, MI,and stroke [30]. Randomization was stratified according tothe method of revascularization determined by the treatingphysician (PCI vs OMT and CABG vs OMT). Therefore,BARI 2D was a trial designed to evaluate coronary revas-cularization as a whole (PCI or CABG) compared withOMT as opposed to comparison of revascularization strate-gy itself (PCI vs CABG). The overall 5-year mortality wasnot different between patients undergoing revascularizationversus OMT as the initial strategy [43]. However, MI(CABG 10.0 % vs OMT 17.6 %, P00.003) and cardiacdeath or MI (CABG 15.8 % vs OMT 21.9 %, P00.03) weresignificantly lower in the CABG group. These benefits werenot noted among patients undergoing PCI as the initialrevascularization strategy, which parallels the findings fromthe COURAGE trial.

Summary and Recommendations

For patients with MV-CAD, outcomes of death, MI, andstroke depend on the extent of disease. The European

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Society of Cardiology (ESC) and the European Associationfor Cardio-Thoracic Surgery (EACTS) guidelines for myocar-dial revascularization incorporate coronary anatomy and le-sion complexity and consider the findings of the SYNTAXtrial [44]. These guidelines incorporate results of the SYN-TAX trial. These recommendations favor CABG over PCI inMV-CAD patients except for those with one- or two-vesseldisease not involving the proximal LAD. In patients withthree-vessel disease with simple lesions where complete re-vascularization can be achieved with PCI (SYNTAX score≤22), PCI receives a Class IIa (level of evidence [LOE] B)recommendation; among those patients with three-vessel dis-ease with SYNTAX score greater than 22 in whom PCI wouldnot be able to achieve complete revascularization, PCIreceives a Class II (LOE A) recommendation.

The recently updated 2011 ACC/AHA guidelines for PCIrecommend a multidisciplinary approach, consisting of aninterventional cardiologist and cardiac surgeon to revascular-ization for complex and unprotected LM-CAD (Class I, LOEC) [45]. Calculation of the SYNTAX score for UPLM andMV-CAD is given a Class IIa (LOE B) recommendation.

Left Main CAD

LM CAD, angiographically defined as greater than 50 %diameter stenosis, is found in 4 % to 6 % of patientsundergoing coronary angiography [46], and when presentis associated with MV-CAD 70 % of the time [47]. Thisreview summarizes when revascularization for LM CAD isindicated and which revascularization strategy is preferred.

When Is Revascularization for Left Main CAD Indicatedand Which Strategy Is Best?

The 2002 ACC/AHA guidelines for management of stableangina assign CABG for LM disease in the presence ofsymptoms or ischemia a Class I recommendation [48]. Ininstances where the angiographic severity of LM disease isuncertain, other factors such as high-risk findings on nonin-vasive testing such as early electrocardiogram changes onexercise stress, a high-risk Duke treadmill score, or myocar-dial perfusion imaging pattern characterized by reduceduptake in the septum and anterior and lateral walls, in-creased lung uptake, or a decline in ejection fraction mayhelp with the decisions to revascularize or not. In the cardiaccatheterization laboratory, a fractional flow reserve (FFR)less than 0.80 or a cross-sectional area less than 5 to 6 mm2

on intravascular ultrasound (IVUS) may help verify angio-graphic findings [49]. In a recent study, IVUS minimallumen area value within the LM that best predicted FFRless than 0.80 was less than 4.8 mm2 (89 % sensitivity, 83 %specificity) [50].

It is abundantly clear that compared with medical therapyalone, revascularization with OMT is beneficial, especiallywhen CABG is the revascularization strategy employed[18]. With improvement in stent technology and medicaltherapy, the proportion of patients undergoing PCI forUPLM-CAD has increased [51]. What is less clear is whichpatients are most likely to derive benefit from PCI forUPLM-CAD. The following sections summarize key dataaddressing this issue.

CABG Versus Medical Therapy for Left Main CAD

Large randomized trials, registries, and meta-analyseshave consistently demonstrated a significant survival ad-vantage with CABG compared with medical therapy onlyfor LM-CAD [52–55]. Based on these findings the 2004ACC/AHA CABG guidelines recommend CABG, as op-posed to medical therapy, in patients with asymptomaticischemia or stable angina and significant LM disease[56].

Stenting of Unprotected Left Main: BMS Versus DES

To date, only one randomized trial has compared the use ofDES versus BMS in LM-CAD in a randomized fashion[57]. In this study of 102 patients with stable angina,patients randomized to paclitaxel-eluting stents had a lowerrate of binary restenosis at 6-month angiographic follow-up(BMS 22 % vs DES 6 %, P00.021) and a higher likelihoodof major adverse cardiac event (MACE) (death, MI, TVRMACE)–free survival (BMS 70 % vs DES 87 %, P00.036)at 6-month clinical follow-up. This reduction was mostlydue to lower TVR in the DES arm (BMS 16 % vs DES 2 %,P00.014).

Two registries noted similar findings. The MAIN-COMPARE (Revascularization for Unprotected Left MainCoronary Artery Stenosis: Comparison of PercutaneousCoronary Angioplasty Versus Surgical Revascularization)registry, which included 1217 patients undergoing stentingof UPLM lesions, showed no significant difference in the 3-year rates of death and MI (BMS 14.9 % vs DES 14.3 %,P00.94) [58]. However, TVR at 3 years was significantlymore common with BMS (BMS 12.1 % vs DES 5.4 %,P<0.001). The LE MANS (Unprotected Left Main StentingVersus Bypass Surgery) registry, which included 252patients undergoing stenting of UPLM lesions, reported asignificantly lower unadjusted rate of MACCE in the DESgroup (DES 15 % vs BMS 26 %, P00.04) [59]. Most of thisdifference was explained by a lower TVR rate in the DESgroup (DES 3.2 % vs BMS 10.1 %, P00.04). Based onthese data, DES are generally preferred for LM PCI in asetting where contraindications to long-term dual antiplate-let therapy are not present.

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DES Versus CABG in Unprotected Left Main CAD

In a prespecified subgroup analysis of patient with LMdisease in the SYNTAX trial (N0705), treatment withCABG versus paclitaxel-eluting stents was not associatedwith a significant difference in the 1-year primary end pointof MACCE (PCI 15.8 % vs CABG 13.7 %, P00.44) [60].Repeat revascularization rate was significantly higher withPCI (PCI 11.8 % vs CABG 6.5 %, P0?). A meta-analysis of1278 patients comparing DES and CABG for the treatmentof UPLM disease demonstrated a significant reduction inMACCE with CABG at median 10-month follow-up(odds ratio 0.46, 95 % CI, 0.24–0.90; P00.02). Of note,this meta-analysis did not include SYNTAX and CARDiaas those data were not yet reported.

Among patients undergoing PCI of LM lesions, out-comes are generally better for patients with ostial or mid-shaft lesions compared with distal LM lesions involving theLAD-circumflex bifurcation [61]. The j-Cypher registryreported a significantly higher target lesion revascularizationrate at 3-year follow-up in patients undergoing LM PCI withSES in distal lesions involving the bifurcation comparedwith ostial/shaft lesions (distal 17.1 % vs ostial/shaft3.6 %, P00.005).

Isolated Left Main CAD

Among patients with LM CAD studied in randomizedclinical trials comparing DES versus CABG, isolated LMCAD comprises 6 % to 13 % of coronary lesions. Todate, no randomized trials dedicated to isolated LM CADexist, and data elucidating the best approach to revascu-larization of such anatomy are derived from subgroupanalyses of larger randomized trials. Among 705 patientswith LM disease in the SYNTAX trials, 91 (12.9 %) hadisolated LM disease. These patients had a numericallylower 12-month MACCE rate when undergoing treat-ment with DES compared with CABG (DES 7.1 % vsCABG 8.5 %) [28••].

Among 600 patients randomized to PCI versusCABG in the PRECOMBAT (Bypass Surgery VersusAngioplasty Using Sirolimus-Eluting Stent in Patientswith Left Main Coronary Artery Disease) study, 61(10.2 %) had isolated LM disease [62]. At 2-yearfollow-up, the composite end point of major adversecardiac and cerebrovascular outcomes (all-cause death,MI, stroke, ischemia-driven TVR) were numericallylower in the DES arm; however, the difference wasnot statistically significant (DES 3.8 % vs CABG8.8 %, HR 0.39, 95 % CI: 0.04, 3.72; P00.41). TheEXCEL (Evaluation of Xience Prime versus CoronaryArtery Bypass Surgery for Effectiveness of Left MainTrial) trial will shed further light on this issue [63].

Summary and Recommendations

The 2011 update of the ACC/AHA PCI guidelines retainedthe Class IIb recommendation for PCI of UPLM-CAD [45].The 2011 update states that PCI of LM with stents may beconsidered as an alternative to CABG in patients with fa-vorable coronary anatomy and clinical conditions that pre-dict an increased risk of adverse surgical outcomes. TheESC/EACTS guidelines favor CABG over PCI for all LMlesions (Class IA) [44]. PCI receives a IIA recommendationfor isolated LM or LM plus one additional vessel disease(LM lesion located in the ostium or mid shaft) and IIBrecommendation for isolated LM disease or LM plus oneadditional vessel (distal LM lesion not involving the bifur-cation) with a SYNTAX score ≤32. A Class III recommen-dation is given to LM PCI in the setting of LM disease and aSYNTAX score ≥33.

Rates of death and MI do not differ in patients withUPLM disease undergoing revascularization with DES orCABG. However, CABG may be associated with ahigher stroke risk. Patients with MV- and LM-CADundergoing revascularization with PCI are more likelyto return for repeat procedures even when treated withDES, as was seen in the SYNTAX trial. Whether repeatrevascularization rates for the treatment of LM-CAD canbe improved with the use of second-generation DES willbe addressed in the EXCEL trial. Until further databecome available, we support the use of DES in isolatedostial and shaft LM lesions for patients without contra-indications to prolonged dual antiplatelet therapy withaspirin and thienopyridine and a proven track record ofadherence to medications. This recommendation standsin contrast to the current practice guidelines, which donot provide a clear distinction for treatment choice basedon anatomic considerations for isolated UPLM-CAD.

Conclusions

Selection of revascularization strategy for MV- or LM-CADcan be a challenge. Revascularization, regardless of thestrategy (PCI vs CABG), is warranted in most patients,especially when symptoms persist despite maximal medicaltherapy. The choice of revascularization strategy remains anindividualized decision factoring in comorbidities, diabetesstatus, functional status, stroke risk, left ventricular function,and complexity of coronary anatomy. Additionally, operatorexpertise and patient preference play a critical role in thedecision process. We recommend collaboration and opendiscussion between the interventional cardiologist, cardiacsurgeon, referring physician, and the patient, with consider-ation of each of these variables to reach the optimaldecision.

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Disclosures No potential conflicts of interest relevant to this articlewere reported.

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