In-Hospital and Long-Term Results of Unprotected Left Main Stenting versus Coronary Artery Bypass Grafting A Single Center Experience in Taiwan

Original Article??? Acta Cardiol Sin 2010;26:216 27 Coronary Artery Disease In-Hospital and Long-Term Results of Unprotected Left Main Stenting versus Coronary Artery Bypass Grafting A Single Center Experience in Taiwan Chun-Cheng Wang, 1 Wei-Jan Chen, 2,4 Feng-Chun Tsai, 3,4 Yu-Shien Ko, 2,4 Chi-Tai Kuo 2,4 and Chi-Jen Chang 2,4 Background: The status of percutaneous coronary intervention (PCI) for the treatment of left main coronary artery (LMCA) disease remains undetermined, and relatively few data on Taiwanese population has been published. Method: Between March, 2003 and October, 2008, 121 patients with de-novo significant LMCA disease were included into this study. Eighty-seven patients received coronary artery bypass surgery (CABG) for LMCA disease, and 34 patients received PCI for LMCA disease. Significant LMCA disease was defined as at least > 50% stenosis of the left main coronary artery. The differences of clinical outcomes between the two treatment strategies were compared with respect to the in-hospital major adverse events rate and long-term major adverse cardiovascular and cerebrovascular events (MACCE) rate. Results: There were no significant differences in terms of baseline characteristics between the two groups. The overall all-cause mortality with MACCE was 32.2% in the CABG group, and 35.3% in the PCI group (p = 0.74). The overall mortality throughout the study period was 17.2% in the CABG group, and 5.9% in the PCI group (p = 0.09). The CABG group had significantly higher in-hospital major adverse event rates (27.6%) than the PCI group (8.8%) (p = 0.02) after adjustment of potential covariates. Long-term cumulative MACCE rates were 15% in the CABG group, and 32.4% in the PCI group, respectively (p = 0.02). The lower MACCE rate in the CABG group was mainly due to lower revascularization rate in the CABG group than in the PCI group (8.8% vs. 29.4%; p < 0.01). Conclusion: The CABG group conferred significantly higher in-hospital major adverse event rate but significantly lower long-term MACCE rate in patients with significant LMCA disease. The CABG group displayed numerically higher incidence of all-cause mortality throughout the study period. PCI could be considered an alternative option for patients with unprotected LMCA disease. Key Words: Complex coronary artery disease Coronary artery bypass surgery Left main coronary artery disease Unprotected left main stenting INTRODUCTION Received: November 19, 2009 Accepted: October 7, 2010 1 Division of Cardiology, Department of Internal Medicine, Taichung Buddhist Tzu-Chi General Hospital, Taichung; 2 First Cardiovascular Division, Department of Internal Medicine; 3 Division of Cardiovascular Surgery, Department of Surgery, Chang-Gung Memorial Hospital; 4 College of Medicine, Chang Gung University, Taoyuan, Taiwan. Address correspondence and reprint requests to: Dr. Chi-Jen Chang, First Cardiovascular Division, Chang-Gung Memorial Hospital, No. 199, Tung Hwa North Road, Taipei, Taiwan. Tel: 886-3-328-1200 ext. 2313; Fax: 886-3-327-1192; E-mail: cchijen@adm.cgmh.org.tw Significant left main coronary artery (LMCA) disease occurs in 5%-7% of patients undergoing coronary angiography. It represents the worst prognosis in any form of coronary artery disease. 1,2 Since the publication of the Coronary Artery Surgery Study registry, coronary artery bypass surgery (CABG) has been judged to confer a survival benefit over simply medical treatment in patients with significant LMCA disease. 3 Currently, the Acta Cardiol Sin 2010;26:216 27 216

CABG versus PCI in de-novo LMCA Disease guidelines still specify percutaneous coronary intervention (PCI) as a class III recommendation for patients with significant LMCA disease who are eligible for CABG. 4 The historically high rate of restenosis and acute thrombotic occlusion has made PCI an inferior strategy to CABG in unprotected left main coronary artery (LMCA) disease. However, the introduction of drug-eluting stents (DESs) has produced a single-digit in-stent restenosis rate and acceptable stent thrombosis rate, renewing interest in PCI treatment of LMCA disease. 5 Several studies have compared CABG and PCI with respect to the early and long-term outcomes in LMCA disease. 1,2,4,6,7 However, these studies have not been conclusive. Moreover, relatively few data on Taiwanese population has been published. METHODS Study design Between March, 2003 and October, 2008, 121 patients were enrolled into the study. All patients had de novo LMCA disease. Significant LMCA disease was defined as at least > 50% stenosis of the LMCA. Patients were divided into two different groups (PCI group and CABG group) with respect to different treatment strategy. Patients who presented with cardiogenic shock were excluded from the study in both groups. In the CABG group, patients who received concomitant valvular replacement or repair during the index bypass surgery were excluded from the study. For all patients who had significant left main disease, we suggested CABG first, but if patients couldn t accept the risk of operation, we discussed with patients and families about PCI treatment for unprotected LMCA lesion. Patients who chose to receive PCI treatment were encouraged to receive drug-eluting stents and prolonged dual anti-platelet therapy for at least 6 months. Coronary angiography follow-up of 6-9 months after the index procedure was suggested to all patients in the PCI group. Assessment of clinical outcome The in-hospital outcome in both groups was compared with the incidence of major adverse events. The long-term clinical outcomes in both groups were compared with the incidence of cumulative all-cause death, cumulative cardiovascular death, cumulative non-fatal myocardial infarction plus cardiovascular death, cumulative non-fatal myocardial infarction, cardiovascular death plus stroke, cumulative revascularization, and cumulative major adverse cardiac and cerebrovascular events (MACCE). The long-term follow-up duration was determined from the time of discharge. The clinical outcomes in both groups were determined from chart records and telephone contact. The cause of death was presumed to be cardiac-related unless proven otherwise. Peri-procedural myocardial infarction (MI) was defined as elevation of serum creatine kinase MB isoenzyme within 7 days after the index procedure that exceeded by five times the normal upper limit in the CABG group, and by three times the normal upper limit in the PCI group. 7 For patients who had elevated creatine kinase MB isoenzyme at baseline, periprocedural MI was defined as an increase (> 50%) of cardiac enzyme activity above baseline in both groups. 7 Target vessel revascularization (TVR) was defined as any revascularization of the treated vessel encompassing any segments of LMCA, left anterior descending artery (LAD) and left circumflex artery (LCX). Target lesion revascularization (TLR) was defined as any revascularization of the target lesion from 5 mm proximal to the stent to 5 mm distal to the stent. 8 Stroke was defined as any permanent neurological deficit confirmed by a neurologist and imaging studies. 1 The major adverse events were defined as allcause mortality, peri-procedural myocardial infarction, repeat revascularization, stroke, major bleeding requiring additional blood transfusion, any major infections or complications compromising post-procedural rehabilitation. The MACCE were defined as any cardiovascular mortality, acute non-fatal myocardial infarction, stroke, and repeat revascularization. 9 In the CABG group, total arterial revascularization was defined as the use of multiple arterial grafts for bypass surgery without saphenous venous grafts. Statistical analysis Categorical variables were presented as percentage, and continuous variables were presented as mean standard deviation or as median and interquartile range. Categorical variables were compared with chi-square test or Fischer s exact test accordingly. The normality assumption for continuous variables was evaluated by the 217 Acta Cardiol Sin 2010;26:216 27

Chun-Cheng Wang et al. Kolmogorov-Smirnov test. Differences in continuous variables between groups of the patients were evaluated using Student s unpaired t tests or Mann-Whitney nonparametric tests, as appropriate. In order to evaluate the independent factors predicting the in-hospital major adverse events rate, we constructed a multivariate binary logistic regression model. The long-term clinical outcomes between the two groups were depicted with Kaplan-Meier curve, and compared with log-rank test. To account for potential confounders, we constructed a multivariable Cox proportional hazards models to estimate the adjusted hazard ratio (HR) of different groups for long-term MACCE rates by adding potential confounders. A p value < 0.05 was considered clinically significant. RESULTS The baseline characteristics of the two groups are presented in Table 1. In the PCI group, a trend toward increased prior revascularization and higher Euroscore was evident, although not statistically significant. Compared to patients in the PCI group, patients in the CABG group displayed an increased, but insignificant, occurrence of chronic obstructive pulmonary disease and significantly increased admission days (30.4 19.4 versus Table 1. Baseline characteristics of the study population CABG group (n = 87) PCI group (n = 34) p value Age 65.7 8.9 67.6 11.3 0.32 a Gender (M/F) 66/21 23/11 0.36 b DM 47(54%) 14(41.2%) 0.20 b HTN 59(67.8%) 26(76.5%) 0.35 b Current smoker 46(52.9%) 18(52.9%) 00.995 b T-Chol 174.9 40.5 171.8 49.0 0.37 d LDL-C 108.0 34.3 106.2 46.2 0.23 d HDL-C 039.0 10.0 39.5 8.8 0.52 d T-Chol/HDL-C 04.7 1.2 04.5 1.6 0.27 d Renal impairment 7(8%)0 3(8.8%) 1.00 c ESRD 4(4.6%) 2(5.9%) 0.67 c Obstructive airway disease 18(20.7%) 2(5.9%) 0.06 c PAOD 16(18.4%) 09(26.5%) 0.32 b Prior revascularization 09(10.2%) 08(23.5%) 0.06 b Prior MI 17(19.5%) 08(23.5%) 0.63 b Prior stroke 11(12.6%) 05(14.7%) 0.76 b Symptom at presentation 0.36 b Angina 39(44.8%) 17(50%)0. Unstable angina 19(21.8%) 05(14.7%) AMI 23(26.4%) 10(29.4%) CHF 6(6.9%) 2(5.9%) Diseased vessels 0.82 b Isolated LMCA disease 3(3.4%) 2(5.9%) LMCA + 1-v-d 09(10.3%) 3(8.8%) LMCA + 2-v-d 23(26.4%) 11(32.4%) LMCA + 3-v-d 52(59.8%) 18(52.9%) EF 61.3% 15.8% 62.0% 13.9% 0.82 a Euroscore 4.4 2.4 5.4 2.9 0.06 a Admission days 30.4 19.4 9.4 4.4 0.01 d CABG, coronary artery bypass graft surgery; PCI, percutaneous coronary intervention; DM, diabetes mellitus; HTN, hypertension; T-Chol, total cholesterol; LDL-Chol, low-density lipoprotein; HDL-Chol, high density lipoprotein; ESRD, end stage renal disease; PAOD, peripheral arterial occlusive disease; MI, myocardial infarction; AMI, acute myocardial infarction; CHF, congestive heart failure; LMCA, left main coronary artery; EF, ejection fraction. Acta Cardiol Sin 2010;26:216 27 218

CABG versus PCI in de-novo LMCA Disease 9.4 4.4 days, p < 0.01). The procedural characteristics of the PCI group are summarized in Table 2. The target lesion of the LM segment was located at the ostial to mid-shaft LMCA in six patients; in these patients, only stent implantation at LMCA and post-dilatation was required, without the need of final kissing ballooning. In the remaining 28 patients, the target lesion was located in the distal LMCA segment; the intervention was more complex and usually required stenting at bifurcation area with final kissing ballooning as indicated. Twenty-eight patients received drug eluting stent (DES) implanted at LMCA lesion. Six patients received bare-metal stent (BMS) at the LMCA lesion. Four patients received BMS at the ostial to shaft LMCA segment because of large vessel size, while two patients received BMS at the distal LMCA segment. No patient received both a drug-eluting stent and a baremetal stent for left main stenting. The total stent number per patient was 2.6 1.1. Final kissing ballooning was performed in 23 of the 28 patients (82.1%) who received distal LMCA stenting. In our study, the paients who received BMS at the LMCA lesion did not have an increased TLR rate compared with the patients who received DES at LMCA lesion (16.7% versus 21.4%, p = 1.00). The procedural characteristics of the CABG group were as follows. Twenty-six patients received off-pump surgery. Total arterial revascularization was performed in 11% of the patients. The mean graft number per patient was 2.1 0.4. Table3summarizesthecomparativedataconcerning the incidence of major adverse events during hospitalization and long-term MACCE for both patient Table 2. Procedural characteristics of PCI group (n = 34) Location of LMCA stenting n = 34 Ostial to shaft LMCA stenting 06 (17.7%) LMCA to proximal LAD stenting 14 (41.2%) LMCA to proximal LCX stenting 1 (2.9%) LMCA to proximal LAD + proximal LCX stenting 13 (38.2%) Stenting techniques for distal LMCA segment Provisional T-stenting 08 (23.5%) V-stenting 04 (11.8%) Crush stenting 2 (5.9%) Single stent approach 14 (41.2%) Stent choice Paclitaxol eluting stent 21 (61.8%) Sirolimus eluting stent 04 (11.8%) Zotarolimus eluting stent 04 (11.8%) BMS 06 (17.7%) IVUS guided LMCA stenting 05 (14.7%) IABP back-up during the procedure 1 (2.9%) Total stent number per patient, mean SD 2.6 1.1 Final kissing after stenting 23 (82.1%) RVD, mean SD 4.1 0.6 mm MVD-pre, mean SD 1.4 0.6 mm MVD-post, mean SD 3.6 0.6 mm LMCA stenosis, pre-intervention, mean SD 67.0% 11.6% LMCA stenosis, post-intervention, mean SD 9.7% 6.1% PCI, percutaneous coronary intervention; LMCA, left main coronary artery; LAD, left anterior descending; LCX, left circumflex artery; BMS, bare-metal stent; IVUS, intravascular ultrasonography; IABP, intraaortic balloon counterpulsation; RVD, reference vessel diameter; MVD-pre, minimal vessel diameter at the left main coronary artery disease segment before intervention; MVD-post, minimal vessel diameter at the left main coronary artery disease segment post-intervention. Total stent number per patient: the total stent numbers implanted during the index procedure. One patients received both paclitaxol eluting-stent and sirolimus eluting-stent at the distal LM segment using V-stent technique; Final kissing after stenting: the proportion of final kissing after stenting was defined as total number of cases with final kissing ballooning procedure divided by total number of distal LMCA disease patients. 219 Acta Cardiol Sin 2010;26:216 27

Chun-Cheng Wang et al. Table 3. Comparison of major adverse events during the hospitalization and MACCE during the long-term follow up During hospitalization CABG group (n = 87) PCI group (n = 34) p value Major adverse events 24 (27.6%) 3 (8.8%) 0.03 a All cause deaths 7 (8.1%) 0 (0.0%) 0.19 a Periprocedural MI 13 (14.9%) 1 (2.9%) 0.11 a Revascularization 1 (1.2%) 0 (0.0%) 1.00 a Stroke 2 (2.3%) 0 (0.0%) 1.00 a Pseudoaneurysm 0 (0.0%) 1 (2.9%) 0.28 a Major bleeding 4 (4.6%) 1 (2.9%) 1.00 a Infection 8 (9.2%) 0 (0.0%) 0.10 a Perforated DU 2 (2.3%) 0 (0.0%) 1.00 a Cardiac tamponade 1 (1.2%) 0 (0.0%) 1.00 a Long-term follow up CABG group (n = 80) PCI group (n = 34) p value MACCE 12 (15.0%) 11 (32.4%) 0.04 b All cause mortality 08 (10.0%) 2(5.9%) 0.38 a Cardiovascular deaths 2 (2.5%) 2 (5.9%) 0.34 a Recurrent MI 6 (7.5%) 1 (2.9%) 0.33 a Revascularization 7 (8.8%) 10 (29.4%) < 0.01 b < Stroke 3 (3.8%) 0 (0.0%) 0.34 a MACCE, major adverse cardiovascular and cerebrovascular events; CABG, coronary artery bypass graft surgery; PCI, percutaneous coronary intervention; MI, myocardial infarction; DU, duodenal ulcer; a, Fischer s exact test; b, chi-square test. groups. The overall all-cause mortality with MACCE, MACCE, and all-cause mortality throughout the study period was not significantly different between the two groups (CABG group vs. PCI group: 32.2% vs. 35.3%, p = 0.74; 27.6% vs. 35.3%, p = 0.40; 17.2% vs. 5.9%, p = 0.09, respectively). However, if clinical outcomes were further divided into in-hospital outcomes and long-term outcomes after discharge, the CABG group had significantly elevated major adverse events rate in comparison to the PCI group (27.6% vs. 8.8%, p = 0.03, respectively). Considering 30-day MACCE as the early clinical outcome, the CABG group exhibited an insignificantly higher 30-day MACCE rate than the PCI group (14.9% versus 2.9%, p = 0.11). There was one peri-procedural non-fatal MI which occurred in the PCI group. Two patients in the PCI group had procedure-related complications. One had procedure-related upper gastrointestinal bleeding requiring additional blood transfusion, and the other patient had right femoral artery pseudoaneurysm. While in the CABG group, 7 patients had in-hospital mortality. One of them died of peri-procedural myocardial infarction with sudden onset of ventricular arrhythmia. Six patients died of procedure-related complication. Thirteen patients had in-hospital peri-procedural myocardial infarction. Two of the 13 patients had acute stroke attack during the index hospitalization. Also, two patients had upper gastrointestinal bleeding post the procedure that required additional blood transfusion. Two patients had mediastinitis that required surgery. Two patients had perforated duodenal ulcer with peritonitis that required surgery. Two patients had empyema. One patient had hemothorax that required pig-tail drainage. One patient had cardiac tamponade that required emergent pericardiocentesis. Three patients had hospital-acquired pneumonia. Considering all potential covariates, the CABG group had significantly higher incidence rate of major adverse events than did the PCI group and was the single independent predictive factor in determining in-hospital major adverse events (p = 0.02) (Table 4). The incidences of long-term MACCE, cardiovascular death, myocardial infarction, revascularization and stroke are summarized in Table 3. Seven patients in the CABG group who died during the index hospitalization were excluded from long-term outcome analysis. The CABG had significantly lower incidence rate of longterm MACCE and revascularization events than did the PCI group (15.0% vs. 32.4%, p = 0.04; 8.8% vs. 29.4%, p < 0.01, respectively). Acta Cardiol Sin 2010;26:216 27 220

CABG versus PCI in de-novo LMCA Disease Table 4. (a) Multivariate binary logistic regression analysis in predicting independent risk factors of in-hospital major adverse events. (b) Cox regression proportional hazard model in predicting long-term MACCE events (a) OR Confidence interval p Groups (CABG versus PCI) 5.13 01.25-21.00 0.02 Age (years) 1.05 0.97-1.14 0.23 EF 1.03 0.99-1.07 0.18 COPD 1.19 0.36-3.93 0.78 Euroscore 1.10 0.80-1.49 0.56 ESRD 0.00 0.00 1.00 Diseased vessels 1.73 0.83-3.58 0.14 DM 1.38 0.52-3.68 0.51 Symptom 1.08 0.61-1.93 0.79 (b) HR Confidence interval p Groups (CABG versus PCI) 0.31 0.13-0.73 0.01 Age (years) 1.02 0.97-1.08 0.38 DM 1.97 0.81-4.79 0.13 ESRD 3.64 00.90-14.79 0.07 EF 0.97 0.95-1.00 0.05 Diseased vessels 1.87 0.90-3.88 0.10 MACCE, major adverse cardiovascular and cerebrovascular events; CABG, coronary artery bypass graft surgery; PCI, percutaneous coronary intervention; EF, ejection fraction; COPD, chronic obstructive pulmonary disease; ESRD, end stage renal disease; DM, diabetes mellitus; OR, odds ratio; HR: hazard ratio. Data on patient death during the study is presented in Supplemental Table 1. The all-cause mortality rates during the index hospitalization and long-term follow up were higher in the CABG group than in the PCI group (8.1% vs. 0%, p = 0.09; 10% vs. 5.9%, p = 0.38), respectively. However, the long-term cardiovascular mortality rate was numerically lower in the CABG group than in the PCI group (2.5% vs. 5.9%, p = 0.34). In the PCI group, no one in the PCI group died during the index hospitalization, and two patients died during the followup period. One died during sleep; in the absence of a defined cause, death was presumed to be cardiovascular in nature. The other patient had recurrent myocardial infarction one year after the index procedure. The followup coronary angiography revealed left main in-stent restenosis, and CABG was suggested. The patient died of cardiogenic shock after the CABG procedure. While in the CABG group, seven patients died in hospital after they received the operation. Of these, only one death was of a cardiovascular cause, with the six other deaths being due to surgical complications. During the longterm follow-up in the CABG group, two patients died of cardiovascular causes. One patient died of concomitant acute stroke and acute ST elevation myocardial infarction 27 months after the index procedure. Data on patient revascularization events is presented in Supplemental Table 2. In the PCI group, 25 of the total 34 patients received follow-up coronary angiography. The coronary angiography follow-up rate was 73.5%. Ten of the total 25 patients who received follow-up coronary angiography had revascularization events. In the PCI group, five patients received revascularization for in-stent restenosis (Cases 1, 6, 8, 9, 10). Four of the five patients received DES implantation at the distal LMCA bifurcation, while one of the patients received BMS at the proximal and distal LMCA (Case 8). Three of the five patients had in-stent restenosis at the ostial LCX segment (Cases 1, 9, 10). One patient who received two-stent technique had in-stent restenosis at multiple sites including the ostial LMCA, ostial LAD, and ostial LCX (Case 9). Three patients received revascularization at distal segments not associated with the LMCA inter- 221 Acta Cardiol Sin 2010;26:216 27

Chun-Cheng Wang et al. vention procedure (Cases 3, 4, 5). Among the five patients who received distal LMCA stenting without final kissing ballooning, two patients had revascularization (Cases 3, 4). However, none of them had target lesion revascularization associated with the index procedure. Supplemental Figure 1 demonstrated results of the comparison of long-term outcomes between the two groups in terms of all cause death, cardiovascular death and cardiovascular death plus nonfatal myocardial infarction with the use of Kaplan-Meier curve and logrank test. The comparison of long-term outcomes between the two groups in terms of cumulative cardiovascular death, nonfatal myocardial infarction plus stoke, and cumulative revascularization are depicted in Supplemental Figure 2. The comparison of long term outcomes between the two groups in terms of MACCE is depicted in Figure 1A. The long-term follow-up duration in CABG and PCI groups was 33 18 months and 27 16 months, respectively (p = 0.05). Cox proportional hazard model was constructed to evaluate risk factors in determining long-term MACCE. The CABG group displayed a significantly lower rate of long-term MACCE than the PCI group after adjusting potential covariates (p < 0.01) (Table 4). The difference of long-term outcomes between the CABG and DES groups was compared in subgroup analysis. There was no incidence of cardiovascular death, non-fatal MI or stroke in the DES group. In the CABG group, higher incidences were evident in the rate of long-term all cause death (10% and 0% in CABG and DES groups, respectively, p = 0.08), cardiovascular death (2.5% and 0%, same respective order, p = 0.55), MI (7.5% and 0%, same respective order, p = 0.16) and stroke (3.8% and 0%, same respective order, p = 0.40). However, the DES group displayed a higher incidence of long-term revascularization (28.6% and 8.8% in the DES and CABG groups, respectively, p = 0.01) and MACCE (28.6% and 15% in the DES and CABG groups, respectively, p = 0.10). Kaplan-Meier curve with logrank test comparison of the long-term outcomes between the CABG and DES groups revealed significantly higher incidences of MACCE (p = 0.02) (Figure 1B), and revascularization (p < 0.01) in the DES group as compared to the CABG group (Supplemental Figure 3). DISCUSSION Our study showed that in patients with significant LMCA disease, surgical intervention produced significantly higher rate of in-hospital major adverse events and longer admission days. The reason the CABG group A Figure 1. (A) Comparison of long-term outcomes in terms of MACCE between the PCI group and CABG group using Kaplan-Maier curve and log-rank test. The solid line represents the PCI group, and the dashed line represents the CABG group. The CABG group displayed significantly lower MACCE rate than the PCI group (p < 0.01). Note in the CABG group, the patients who died during the index hospitalization (n = 7) were excluded from the long-term outcome analysis. The PCI group includes both the BMS (bare-metal stent) group and the DES (drug-eluting stent) group. (B) Comparison of long-term outcomes in terms of cumulative revascularization and MACCE between the CABG group and DES group using Kaplan-Meier curve and log-rank test. The CABG group displayed significantly lower rates of MACCE than the DES group (p = 0.02). Note in the CABG group, the patients who died during the index hospitalization (n = 7) were excluded from the long-term outcome analysis. B Acta Cardiol Sin 2010;26:216 27 222

CABG versus PCI in de-novo LMCA Disease produced higher in-hospital major adverse events may be inherent to the procedure itself. In our data, the CABG group produced increased rates of periprocedural MI (p = 0.11) and infection (p = 0.10) than did the PCI group. The increased rate of periprocedural MI may be due to hemodynamic compromise during anesthesia, possible inadequate myocardial protection during the bypass surgery, and myocardial ischemia secondary to aortic cross clamping. 10 None of those procedures are required during the percutaneous intervention. The increased rate of infection may also be explained by the more invasive nature of the bypass surgery. Lee et al. has reported that CABG patients exhibited a higher 30-day MACCE rate than PCI patients (17% versus 2%, p < 0.01). 2 Hsu et al. also reported that CABG patients displayed an insignificant trend toward worse early 30-day MACCE rate than did PCI patients (25.6% versus 5%, respectively, p = 0.05). 11 Our results were comparable to those in their reports. We observed that the CABG group had a significantly better long-term freedom from MACCE mainly due to a lower rate of revascularization. 12 Several reasons might explain that. First, if patients survived the index procedure, the blood flow supply distal to the LMCA was mostly protected by two or more grafts, thus providing potentially long-term safety and fewer cardiovascular events than the PCI group, in which the restenosis near the LMCA segment might pose a larger area of myocardial ischemia. Second, in the PCI group, most patients received routine follow-up coronary angiography. While the CABG group received follow-up coronary angiography only when ischemic symptoms were present or ischemia was revealed by stress tests. As a result, graft occlusion may have been clinically underestimated. Third, the PCI treated only the diseased segment. In our cases, three of the 10 revascularization events were due to the newly diseased segments not associated with the index procedure itself. Chieffo et al. reported that up to 1 year, the PCI group showed significantly higher rate of revascularization than the CABG group. 4 Seung et al. showed no significant differences in rates of death or of the composite end point of death, Q-wave MI or stroke for up to three years between the two groups. However, the PCI group showed a significantly higher rate of revascularization than the CABG group. 1 The findings of the present study were consistent with these previous studies. In this study, there was no discernable superiority of the DES over the BMS in LMCA stenting in terms of target lesion revascularization (p = 1.00), possibly because of differently covered segments. We used DES for distal LMCA bifurcation in twenty-six of the total twenty-eight patients. BMS was used for ostial to midshaft LMCA lesion in four of the total six patients because of large reference diameter. The distal LMCA segment in itself had higher rate of restenosis than the ostial- to mid-shaft LMCA segment. In our study, the CABG group had higher rates of in-hospital all-cause mortality, and long-term all-cause mortality, but had lower rate of long-term cardiovascular mortality. The higher rate of in-hospital all-cause mortality was mainly due to procedure-related complications. Though CABG provided a better long-term result, the potential risk of early post-operative complications inherent to the procedure itself cannot be ignored. The PCI group provided an insignificantly higher rate of long-term cardiovascular mortality. In the PCI group, both patients died of cardiovascular causes. One thing that should be mentioned is that both of the patients received bare-metal stents. Several studies have discussed the role of drug-eluting stent in LMCA stenting, which could reduce the cardiac mortality. 13,14 Valgimigli et al. already reported LMCA stenting with DES significantly reduced cumulative incidence of major adverse cardiovascular events (MACE), nonfatal MI, and revascularization compared with BMS. 15 Moreover, restenosis of LMCA disease after stent implantation might play an important role in cardiovascular mortality. 16,17 DES for LMCA disease might reduce the long-term cardiovascular mortality resulted from BMS placement. Based on our result, the DES group displayed a lower rate of long-term cardiovascular mortality than the CABG group. Though in the drug-eluting stent era, DES may provide an alternative treatment for unprotected LMCA disease, two obstacles remain unsolved. Firstly, there s no drug- eluting stent currently available that can be expanded above 4.5 mm, which is often the diameter in the ostium or mid-shaft location of the LMCA. Secondly, none of the current two-stent technique strategies meet the durability standard that we expect for coronary revascularization with DES (with a 2% stent thrombosis rate and 20-44% angiographic restenosis rate). 18 223 Acta Cardiol Sin 2010;26:216 27

Chun-Cheng Wang et al. Study limitation The present study has several limitations. It was retrospective and observational in nature. Moreover, because of the limited case number, no definitive conclusions can be drawn about whether PCI can achieve a long-term result similar to that of CABG. Thirdly, even though the baseline characteristics within the two groups were compared and no statistically significant differences were evident, we still cannot conclude that both groups had the same coronary artery complexity. 19 Finally, seven patients in the CABG group who perished during the index hospitalization were excluded from the analysis of long-term clinical outcomes. The favorable long-term results of the CABG group could be influenced by selection bias. CONCLUSION Our data showed that, compared with CABG group, patients with unprotected LMCA disease treated with PCI had comparable results in terms of overall all-cause mortality with MACCE throughout the study period. The PCI group had numerically lower rate of overall all-cause mortality throughout the study period. The PCI group displayed significantly lower in-hospital major adverse events, fewer periprocedural complications, and fewer admission days, but had significantly higher incidence of MACCE during long-term follow-up in large part because of higher revascularization rate. Based on our data, PCI treatment for significant LMCA disease could be considered in patients as an alternative approach. REFERENCES 1. 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;358:1781-92. 2. 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;47:864-70. 3. Caracciolo EA, Davis KB, Sopko G, et al. 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CABG versus PCI in de-novo LMCA Disease 18. Baim DS, Mauri L, Cutlip DC. Editorial comment: drug-eluting stenting for unprotected left main coronary artery disease. Are we ready to replace bypass surgery? J Am Coll Cardiol 2006;47: 878-81. 19. Ong ATL, Serruys PW, Mohr FW, et al. The SYNergy between percutaneous intervention with TAXus and cardiac surgery (SYNTAX) study: design, rationale, and run-in phase. Am Heart J 2006;151:1194-204. SUPPLEMENT Supplemental Table 1. Causes of death during the hospitalization and the follow up period No M/F Procedure Age EF Cause of death Time 1 M CABG 70 y/o 48% Sepsis due to prolonged intubation, post-stroke status Within index hospitalization 2 F CABG 75 y/o 69% Sepsis due to pneumonia and decubitus ulcer, ARF requiring H/D Within index hospitalization 3 M CABG 68 y/o 29% Septic shock due to mediastinal abscess Within index hospitalization 4 M CABG 71 y/o 66% Acute perforation peritonitis secondary to duodenal ulcer Within index hospitalization 5 M CABG 70 y/o 36% Septic shock due to mediastinal abscess Within index hospitalization 6 M CABG 80 y/o 33% Septic shock with ARF due to empyema and pneumonia Within index hospitalization 7 M CABG 66 y/o 74% Sudden onset of VT/Vf due to recurrent MI Within index hospitalization 8 F CABG 69 y/o 59% Sudden death suspect due to recurrent MI 27 months 9 M CABG 67 y/o 39% Recurrent MI with cardiogenic shock 02 months 10 M CABG 67 y/o 53% Pneumonia complicated with ARDS 12 months 11 M CABG 74 y/o 75% Colon cancer with distant metastasis 20 months 12 M CABG 67 y/o 64% ICH due to falling down 30 months 13 F CABG 52 y/o 48% Septic shock due to pneumonia 25 months 14 M CABG 65 y/o 77% Septic shock due to catheter related infection 44 months 15 M CABG 72 y/o 83% Bed ridden, sepsis due to pneumonia and UTI 27 months 16 M PCI 78 y/o 41% Unexplained death during sleep suspect cardiovascular cause 29 months 17 F PCI 63 y/o 71% Recurrent MI due to LMCA in stent restenosis 12 months M, male; F, female; CABG, coronary artery bypass surgery; PCI, percutaneous coronary intervention; EF, ejection fraction; ARF, acute renal failure; ARDS, acute respiratory distress syndrome; ICH, intracerebral hemorrhage; LMCA, left main coronary artery; VT, ventricular tachycardia; Vf, ventricular fibrillation; UTI, urinary tract infection; MI, myocardial infarction. Supplemental Table 2. Procedural characteristics and angiographic results of patients who had revascularization events Case Stent Procedure/Kissing ballooning 1 PES Crush/+ PES 3.5 32 mm at LMCA to LAD PES 2.75 24 mm at LMCA to LCX Stenting location Revascularization site Managment LM to LAD, ostial LCX ISR Mid-LM stenting; balloon dilatation at LAD, LCX 2 PES single stent/+ PES 3.0 32 mm at LMCA to LAD Ostial LCX stenosis stenting 3 SES single stent/- SES 3.5 18 mm at LMCA to LAD Distal LCX to OM2 stenosis stenting 4 PES single stent/- PES 3.5 20 mm at LMCA to LAD Mid- LAD stenosis Balloon dilatation 5 BMS single stent/+ Multi-Link Penta stent 3.0 8mmat Distal LCX to OM2 stenosis CABG distal LMCA to ostial LAD 6 PES, V-stenting/+ PES 3.0 16 mm at LMCA to LAD Proximal LCX ISR Balloon dilatation SES SES 2.5 23 mm at LMCA to LCX 7 PES single stent/+ PES 3.5 24 mm at LMCA to LAD Ostial LCX stenosis Stenting 8 BMS stenting at ostial and distal LMCA Carbostent 3.5 12 mm at ostial LMCA Express 3.5 8 mm at distal LMCA Both ostial LM and distal LM ISR, proximal LAD stenosis CABG 9 PES T-stenting/+ PES 3.0 32 mm at LMCA to LCX LM, ostial LAD and ostial LCX ISR Balloon dilatation PES 2.75 32 mm at LAD 10 PES T-stenting/+ PES 3.0 28 mm at LMCA to LAD PES 2.5 28 mm at LCX Ostial LCX ISR, distal LCX stenosis Balloon dilatation PES, paclitaxel-eluting stent; SES, sirolimus-eluting stent; LMCA, Left main coronary artery; LAD, Left anterior descending artery; LCX, Left circumflex artery; OM, Obtuse marginal branch; ISR, Instent restenosis; CABG, Coronary artery bypass surgery. 225 Acta Cardiol Sin 2010;26:216 27

Chun-Cheng Wang et al. A B C Supplemental Figure 1. Comparison of long-term outcomes in terms of all cause death, cardiovascular death, cardiovascular death plus MI between the PCI group and CABG group using Kaplan- Maier curve and log-rank test. The solid line represents the PCI group, and the dashed line represents the CABG group. (A) No significant differences were evident in cumulative all cause death, (B) Cumulative cardiovascular death, (C) Cumulative cardiovascular death plus nonfatal MI. Note in the CABG group, the patients who died during the index hospitalization (n = 7) were excluded from the long-term outcomes analysis. The PCI group includes both the BMS(bare-metal stent) group and the DES (drug-eluting stent) group. A Supplemental Figure 2. Comparison of long term outcomes in terms of cardiovascular death + nonfatal MI + Stroke, and cumulative revascularization between the PCI group and CABG group using Kaplan-Maier curve and log-rank test. The solid line represents the PCI group, while the dashed line represents the CABG group. (A) No significant difference was evident in cumulative incidence of cardiovascular death + nonfatal MI + stroke, (B) The PCI group displayed significantly higher incidence of cumulative revascularization as compared to the CABG group (p < 0.01). Note in the CABG group, the patients who died during the index hospitalization (n = 7) were excluded from the long-term outcomes analysis. The PCI group includes both the BMS (bare-metal stent) group and the DES (drug-eluting stent) group. B Acta Cardiol Sin 2010;26:216 27 226

CABG versus PCI in de-novo LMCA Disease Supplemental Figure 3. Comparison of long-term outcomes in terms of cumulative revascularization between the CABG group and DES group using Kaplan-Meier curve and logrank test. The CABG group displayed significantly lower rates of revascularization than the DES group (p < 0.01). Note in the CABG group, the patients who died during the index hospitalization (n = 7) were excluded from the long-term outcomes analysis. 227 Acta Cardiol Sin 2010;26:216 27