In the field of interventional cardiology, drug-eluting stent

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1 Summary Three-Year Clinical and Angiographic Outcomes After Everolimus-Eluting Stent Implantation in Patients With a History of Coronary Artery Bypass Grafting Takahiro Nomura, 1 MD, Nobuaki Suzuki, 1 MD, Shintaro Takamura, 1 MD, Hiroyuki Kyono, 1 MD, and Ken Kozuma, 1 MD The clinical and angiographic outcomes after percutaneous coronary intervention (PCI) with everolimus-eluting stent (EES) implantation in patients with a history of coronary artery bypass grafting (CABG) have yet to be fully investigated. The aim of the present study was to investigate 3-year clinical outcomes after EES implantation in patients with a history of CABG. We retrospectively enrolled 176 consecutive patients who had undergone EES implantation. Three-year clinical follow-up data were obtained from all patients. Follow-up angiograms and serial quantitative coronary angiography analysis (QCA) were performed for 139 (79.0%) patients. Patients from the prior CABG (+) group (n = 17; 9.7%) had higher incidences of target lesion revascularization (TLR; 41.2% versus 3.8%, P < 0.001) and major adverse cardiac events (47.1% versus 15.1%, P = 0.004). A landmark analysis conducted 1 year into our study showed a higher incidence of TLR in the prior CABG (+) group (20.0% versus 3.0%, P = 0.017). The reason for EES implantation in the prior CABG (+) group was saphenous vein graft (SVG) failure in 19 (79.2%) lesions, although the target vessel was the SVG in 8 (33.3%) lesions. There were no significant differences in clinical and follow-up QCA data between the native vessel and SVG PCI groups. This study revealed that a history of CABG was a risk factor for TLR after EES implantation. The major reason for PCI after CABG was SVG failure; both native vessel and SVG PCI showed poor outcomes. Further investigations may be warranted to determine which interventions are most effective in this high-risk subset. (Int Heart J 2016; 57: ) Key words: Coronary artery disease, Coronary artery bypass surgery, Diabetes, Smoking In the field of interventional cardiology, drug-eluting stent (DES) implantation is the standard therapy for coronary artery disease (CAD). 1,2) Currently, everolimus-eluting stent (EES) implantation is one of the most widely used and clinically validated DES in the world. 1) Previous studies have demonstrated the safety and efficacy of EES implantation in a daily clinical setting. 3-5) The RESOLUTE All-Comers study demonstrated that the long-term clinical outcome and overall results of EES are favorable. 6) However, several patient subsets show poor clinical and angiographic outcomes after EES implantation. Of these, patients with a history of coronary artery bypass grafting (CABG) show higher revascularization rates than those with no history of CABG. 7) The risk factors for restenosis after EES implantation in patients with a history of CABG have yet to be fully investigated. The aim of this study was to investigate 3-year clinical outcomes after EES implantation in patients with a history of CABG. Methods We retrospectively enrolled 176 consecutive Japanese patients (252 lesions) who underwent successful EES implantation from January 2010 to September 2011 at our institution. The study patient flow is illustrated in Figure 1. The study was approved by our institutional ethics committee and the necessity for informed consent was waived according to the Japanese standard ethical policy established by the Ministry of Health, Labor and Welfare. We have no disclosures to make regarding this investigation. The observers were blinded to the patient demographics during analysis of the quantitative images. Two types of EES were available for use in the study: Xience V TM (Abbott Vascular, Santa Clara, CA, USA; diameters of 2.50, 2.75, 3.00, and 3.50 mm and lengths of 8, 12, 15, 23, and 28 mm) and Promus Element TM (Boston Scientific, Natick, MA, USA; diameters of 2.50, 2.75, 3.00 and 3.50 mm and lengths of 8, 12, 16, 20, 24, and 28 mm). When loading of dual antiplatelet drugs was necessary, patients received 300 mg From the 1 Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan. Address for correspondence: Nobuaki Suzuki, MD, Department of Medicine, Teikyo University School of Medicine, Kaga, Itabashi-ku, Tokyo, Japan. nsuzu@bronze.ocn.ne.jp Received for publication August 9, Revised and accepted September 25, Released in advance online on J-STAGE March 11, (This is Advance Publication.) All rights reserved by the International Heart Journal Association. 158

2 Vol 57 No 2 EVEROLIMUS-ELUTING STENT IMPLANTATION AFTER CABG 159 Figure 1. Patient flow. We enrolled 176 consecutive patients (252 lesions) who underwent percutaneous coronary intervention (PCI) with everolimus-eluting stent (EES) implantation. Of these, 17 patients had a history of coronary artery bypass grafting (CABG). Of their 24 lesions, PCI was performed in 19 lesions due to saphenous vein graft (SVG) failure. The target vessel was SVG in 8 lesions. Clinical 3-year follow-up data was obtained from all patients. of aspirin and 300 mg of clopidogrel before PCI. In addition, 2000 units of heparin were administered every hour during PCI to keep activated clotting time over 200 seconds. The standard antiplatelet regimen in our institution is 100 mg/day of aspirin given indefinitely and thienopyridine (75 mg/day of clopidogrel or 200 mg/day of ticlopidine) for at least 12 months. The duration of dual antiplatelet therapy was left to the discretion of each attending physician. Our standard EES implantation strategy is as follows: 1) full-coverage stenting and adequate stent sizing are planned, 2) non-compliant balloon dilatation is usually performed to minimize incomplete stent apposition, 3) additional short-stent implantation is performed for stent edge dissection, 4) singlestent plus provisional kissing balloon technique is performed for bifurcation lesions except for those with a Medina classification score of (1,1,1), 5) for patients with ST-segment elevation myocardial infarction, thrombectomy and distal protection device are used, and 6) an intravascular imaging device (intravascular ultrasound or optical coherence tomography) is used for optimizing the stenting. Otherwise, the selection of adjunctive procedures before and after EES implantation was left to the discretion of the operator. Qualitative coronary angiography assessment was performed in accordance with the standard definition, as used in previous investigations. 3,4) Quantitative coronary angiography was evaluated using QAngio XA 7.2 (Medis, Leiden, Netherlands). Baseline, post-procedure, and follow-up data were obtained. In addition to systematic 8-month follow-up angiograms, clinically-driven angiograms (if performed before the follow-up period) were also analyzed as follow-up data. The target segment was defined as the entire segment involving the implanted stent and the 5-mm proximal and distal edges adjacent to the stent, as previously described. 8,9) A segment to be treated with multiple overlapping stents was regarded as a single target segment. Binary restenosis (BR) was defined as a diameter stenosis (DS) 50%. Clinical events were followed up in September 2014 for all patients. The follow-up period was at least 3 years and up to 4 years. Systematic angiographic follow-up was scheduled at approximately 8 months after EES implantation, with the patient s consent. The primary endpoints were target lesion revascularization (TLR) and major adverse cardiac events (MACE; all-cause death, myocardial infarction, and TLR). Secondary endpoints were in-segment DS and BR. Statistics: Continuous variables are expressed as the mean ± standard deviation and compared by means of paired and unpaired t tests and one-way ANOVA. Categorical variables are expressed as frequencies, and a comparison was performed according to chi-square and Fisher s exact tests. Kaplan Meier curve analysis and the log-rank test were performed to test the predictive value of a history of CABG surgery for TLR and MACE. A multivariate Cox regression analysis was performed to identify independent predictors of TLR. A P value of < 0.05 was considered statistically significant, and all reported P-values were two-sided. Statistical analyses were performed using SPSS statistics 20 (SPSS Inc., Chicago, IL, USA). Results Of the 176 patients enrolled, 17 (9.7%) had a history of CABG surgery [prior CABG (+)]. Angiographic follow-up was performed for 139 (79.0%) patients (Figure 1). Angiographic follow-up was not performed under the following conditions: death (12 patients), renal dysfunction (7 patients), patient choice (7 patients), miscellaneous reasons (7 patients), and test deferred beyond 1 year (4 patients). The average duration from CABG surgery to EES implantation was 6.9 ± 6.9 years. First, all patients and lesions were divided into two groups; prior CABG (+) and CABG (-) groups. Table I shows the comparison of patient characteristics between the two groups. There was no significant difference in patient demographics between the two groups, except that diabetes, insulintreated diabetes, dyslipidemia, prior stroke, and peripheral vessel disease were more frequently observed in the prior CABG (+) group. Regarding lesion characteristics, target lesions were more frequently located at the right coronary artery and saphenous vein graft (SVG) and less frequently at the left anterior descending coronary artery in the prior CABG (+) group. Nineteen (79.2%) lesions in 12 patients (70.6%) from the prior CABG (+) group were treated due to SVG failure. A poorer pre-timi grade was observed in the prior CABG (+) group. With respect to qualitative lesion assessment, American College of Cardiology/American Heart Association lesion classification type C and in-stent restenosis were more frequently observed in the prior CABG (+) group. Clinical outcomes for the prior CABG (+) group are shown in Table II. During the observation period, TLR was performed on 13 (7.4%) patients, and MACE was observed in 32 (18.2%) patients. Most TLR were clinically driven. The incidences of MACE and TLR were significantly higher in the prior CABG (+) group than in the CABG ( ) group. We performed multivariate Cox regression analyses to identify the predictors of TLR. Prior CABG

3 160 NOMURA, ET AL Int Heart J March 2016 Table I. Patient and Lesion Characteristics in the Prior Coronary Artery Bypass Grafting: CABG (+) and CABG ( ) Groups Prior CABG (+) Prior CABG ( ) P Patient characteristic n = 17 n = 159 Age, years ± ± Male, n (%) 12 (70.6%) 124 (78.0%) Body mass index, (kg/m 2 ) ± ± Hypertension, n (%) 13 (76.5%) 131 (82.4%) Diabetes, n (%) 13 (76.5%) 73 (45.9%) Insulin treated diabetes, n (%) 6 (35.3%) 11 (6.9%) Dyslipidemia, n (%) 16 (94.1%) 106 (66.7%) Hemodialysis, n (%) 3 (17.6%) 9 (5.7%) Chronic kidney disease ( Grade 3a), n (%) 11 (64.7%) 82 (51.6%) Current smoking, n (%) 4 (23.5%) 33 (20.8%) Prior myocardial infarction, n (%) 7 (41.2%) 71 (44.7%) Prior stroke, n (%) 5 (29.4%) 16 (10.1%) Peripheral vessel disease, n (%) 7 (41.2%) 16 (10.1%) Anemia (Hb < 11 g/dl), n (%) 5 (29.4%) 30 (18.9%) Previous PCI, n (%) 9 (53.0%) 76 (47.8%) Diagnosis, n (%) Stable coronary artery disease 11 (64.7%) 105 (66.0%) Silent myocardial ischemia 1 (5.9%) 2 (1.3%) Unstable angina 2 (11.8%) 36 (22.6%) STEMI 1 (5.9%) 8 (5.0%) NSTEMI 2 (11.8%) 5 (3.1%) Recent myocardial infarction 0 (0%) 2 (1.3%) LVEF < 30%, n (%) 2 (11.8%) 5 (3.1%) Multivessel disease treatment, n (%) 3 (17.6%) 31 (19.5%) Procedural characteristics Number of stent, n 2.12 ± ± IVUS guidance, n (%) 16 (94.1%) 151 (95.0%) OCT guidance, n (%) 1 (5.9%) 12 (7.5%) Distal protection, n (%) 1 (5.9%) 9 (5.7%) Thrombectomy, n (%) 1 (5.9%) 9 (5.7%) IABP support, n (%) 1 (5.9%) 3 (1.9%) Lesion characteristics n = 24 n = 228 Target vessel, n (%) < RCA 8 (33.3%) 54 (23.7%) LAD 2 (8.3%) 109 (47.8%) LCX 3 (12.5%) 57 (25.0%) LM 3 (12.5%) 8 (3.5%) SVG 8 (33.3%) 0 (0%) Due to SVG failure, n (%) 19 (79.2%) NA NA Pre TIMI grade, n (%) (25%) 22 (9.6%) 1 0 (0%) 2 (0.9%) 2 6 (25%) 16 (7.0%) 3 12 (50%) 188 (82.5%) ACC/AHA lesion classification, n (%) < A 1 (4.2%) 40 (17.5%) B1 4 (16.7%) 78 (34.2%) B2 3 (12.5%) 60 (26.3%) C 16 (66.7%) 50 (22.0%) In-stent restenosis, n (%) 7 (29.2%) 26 (11.4%) Lesion length, n (%) < 10 mm 11 (45.8%) 111 (48.7%) 10~20 mm 8 (33.3%) 78 (34.2%) > 20 mm 5 (20.8%) 39 (17.1%) Thrombus, n (%) 1 (4.2%) 4 (1.8%) Eccentric, n (%) 3 (12.5%) 34 (15.0%) Angulated, n (%) < 45 degree 22 (78.6%) 223 (97.8%) 45~90 degree 1 (4.2%) 5 (2.2%) > 90 degree 1 (4.2%) 0 (0%) Calcification, n (%) None or mild 17 (70.8%) 189 (82.9%) Moderate 3 (10.7%) 14 (6.1%) Severe 4 (14.3%) 25 (11.0%) Ulceration, n (%) 1 (4.2%) 2 (0.9%) Tortuosity, n (%) 0.125

4 Vol 57 No 2 EVEROLIMUS-ELUTING STENT IMPLANTATION AFTER CABG 161 None or mild 20 (83.3%) 204 (89.5%) Moderate 3 (12.5%) 16 (7.0%) Severe 1 (4.2%) 8 (3.5%) Ostial, n (%) 4 (14.3%) 18 (7.9%) Bifurcation, n (%) 7 (29.2%) 81 (35.5%) Medina 1,1,1, n (%) 2 (8.3%) 12 (5.3%) 0.63 Chronic total occlusion, n (%) 5 (20.8%) 19 (8.3%) Aneurysm, n (%) 1 (4.2%) 2 (0.9%) Post TIMI grade, n (%) (0%) 0 (0%) 1 0 (0%) 0 (0%) 2 2 (8.3%) 7 (3.1%) 3 22 (91.7%) 221 (97.0%) Post procedural distal embolism, n (%) 0 (0%) 3 (1.3%) CABG indicates coronary artery bypass grafting; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction; NSTEMI, non ST-elevation myocardial infarction; LVEF, left ventricular ejection fraction; IVUS, intravascular ultrasound; OCT, optical coherence tomography; IABP, intra-aortic balloon pumping; RCA, right coronary artery; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; LM, left main coronary artery; SVG, saphenous vein graft; TIMI, thrombolysis in myocardial infarction; and ACC/AHA, American College of Cardiology/American Heart Association. Table II. Clinical Outcomes in the Prior CABG (+) and CABG ( ) Groups Prior CABG (+) Prior CABG ( ) P Patient outcome n = 17 n = 159 MACE, n (%) 8 (47.1%) 24 (15.1%) Death, n (%) 1 (5.9%) 15 (9.0%) 1.0 Myocardial infarction, n (%) 0 (0%) 3 (1.9%) 1.0 Target lesion revascularization, n (%) Any 7 (41.2%) 6 (3.8%) < Clinically driven 6 (35.3%) 5 (3.1%) < Any revascularization, n (%) 11 (64.7%) 36 (22.6%) < PCI, n (%) 11 (64.7%) 29 (18.2%) < CABG, n (%) 0 (0%) 7 (4.4%) Target vessel failure, n (%) 8 (47.1%) 20 (12.6%) < Non target vessel failure, n (%) 5 (29.4%) 23 (14.5%) Any readmission, n (%) Ischemic heart disease, n (%) 10 (58.8%) 29 (18.2%) Non-ischemic heart disease, n (%) 0 (0.0%) 4 (2.5%) Non-heart disease, n (%) 3 (17.6%) 24 (15.1%) Angiographic outcomes n = 20 n = 172 Follow-up TIMI grade, n (%) (5%) 1 (0.6%) 1 0 (0%) 0 (0%) 2 2 (10%) 1 (0.6%) 3 17 (85%) 170 (98.8%) Thrombus, n (%) 1 (5%) 0 (0%) Aneurysm, n (%) 0 (0%) 1 (0.6%) Peri-stent contrast staining, n (%) 1 (5%) 0 (0%) Stent fracture, n (%) 1 (5%) 0 (0%) MACE indicates major adverse cardiac events; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; and TIMI, thrombolysis in myocardial infarction. was a predictor of TLR (P < 0.001; hazard ratio (HR): 13.62; 95% confidential interval (CI): ), independent of current smoker (P = 0.036; HR: 3.68; 95% CI: ), anemia (hemoglobin < 11.0 g/dl; P = 0.037; HR: 3.55; 95% CI: ), hemodialysis (P = 0.34; HR: 2.35; 95% CI: ), dyslipidemia (P = 0.42; HR: 2.45; 95% CI: ), peripheral artery disease (P = 0.74; HR: 0.75; 95% CI: ), and diabetes (P = 0.82; HR: 0.87; 95% CI: ). A comparison of the cumulative incidences of clinical events between the two groups is shown in Figure 2. The prior CABG (+) group showed a higher incidence of TLR and MACE. The results of the 1-year landmark analysis are shown in Figure 3. The prior CABG (+) group showed a higher incidence of TLR (20.0% versus 3.0%, P = 0.017; log-rank test) although the difference in MACE (20.0% versus 7.6%, P = 0.220; log-rank test) was insignificant. Quantitative coronary analysis (QCA) data from the two groups is shown in Table III. No difference was observed between the two groups at baseline, except that diameter stenosis before the index procedure and in-segment acute gain was greater in the prior CABG (+) group. Follow-up data also shows that late loss and DS were significantly higher in the prior CABG (+) group at in-stent and in-segment subsegments. Table IV reveals the comparison of patient demographics

5 162 NOMURA, ET AL Int Heart J March 2016 Figure 2. Cumulative incidence of events through 3-year follow-up. Cumulative major adverse cardiac events and target lesion revascularization rates were higher in the prior coronary artery bypass grafting (+) group. Figure 3. Landmark analysis for cumulative incidence of events. One-year landmark analysis revealed that the incidence of TLR of the prior CABG (+) group was significantly higher. and lesion characteristics between patients with and without TLR in the prior CABG (+) group. Current smoking and insulin-treated diabetes were more frequently observed in the prior CABG TLR (+) groups. There was no significant difference in the rate of SVG treatment between the two groups. The results of a lesion-based comparison in clinical and angiographic outcomes between native vessel and SVG PCI subgroups in the prior CABG (+) group are shown in Figure 4. There was no significant difference in TLR rate (31.3% versus 37.5%, P = 1.0), follow-up in-segment DS (46.4 ± 26.4% versus 37.2 ± 23.1%, P = 0.448) and follow-up in-segment BR (35.7% versus 33.3%, P = 1.0) between the two groups. Discussion In this study, the following results were noted among patients who underwent EES implantation: 1) a higher incidence of clinical events (TLR and MACE) and a greater BR rate was observed in the prior CABG (+) group, 2) a landmark analysis conducted 1 year into the study showed a higher incidence of TLR, 3) in the prior CABG (+) group, the main reason for EES implantation was SVG failure, despite the target vessel being SVG only in one-third of lesions, 4) no significant differences in TLR rate, in-stent late loss, and DS were observed between the SVG PCI and native vessel PCI groups in the prior CABG (+) group, and 5) current smoking and insulin-treated diabetes were more frequently observed in the prior-cabg TLR (+) groups. The strengths of this study are the following: First, only patients with EES implantation were enrolled. Second, this paper presents 3-year follow-up data. It is known that late restenosis and late TLR beyond 1 year are common in DES use. 10) A previous paper has shown that even 2nd generation DES have the risk of neoatherosclerosis which appears

6 Vol 57 No 2 EVEROLIMUS-ELUTING STENT IMPLANTATION AFTER CABG 163 Table III. Quantitative Coronary Analysis Data Prior CABG (+) Prior CABG ( ) P Pre-procedure n = 24 n = 228 Lesion length, mm 9.31 ± 5.10 (17) 10.5 ± 5.5 (204) Reference vessel diameter, mm 2.48 ± ± Minimal lumen diameter, mm 0.65 ± ± Diameter stenosis, % 74.6 ± ± Post-procedure Stent length, mm 26.6 ± ± Reference vessel diameter, mm 2.49 ± ± Minimal lumen diameter, mm In-stent 2.25 ± ± In-segment 1.92 ± ± Diameter stenosis, % In-stent 15.0 ± ± In-segment 22.9 ± ± Acute gain, mm In-stent 1.60 ± ± In-segment 1.26 ± ± At follow-up n = 20 n = 172 Reference vessel diameter, mm 2.85 ± ± Minimal lumen diameter, mm In-stent 1.69 ± ± In-segment 1.58 ± ± Diameter stenosis, % In-stent 44.3 ± ± 13.8 < In-segment 43.7 ± ± 14.4 < Late loss, mm In-stent 0.61 ± ± 0.41 < In-segment 0.39 ± ± Binary restenosis, n (%) In-stent 7 (35.0%) 4 (2.3%) < In-segment 7 (35.0%) 8 (4.7%) < CABG indicates coronary artery bypass grafting. Figure 4. Differences in clinical and angiographic outcomes between native vessel percutaneous coronary intervention (PCI) group and saphenous vein graft (SVG) PCI groups. Despite higher lesion-based target lesion revascularization (TLR) rates, in-segment diameter stenosis (DS) and binary restenosis (BR) at follow-up in the CABG (+) group, no significant difference in these parameters were observed between the native vessel percutaneous coronary intervention (PCI) group and saphenous vein graft (SVG) PCI groups.

7 164 NOMURA, ET AL Int Heart J March 2016 Table IV. Patient and Lesion Characteristics in Target Lesion Revascularization: TLR (+) and TLR ( ) Groups of Prior CABG (+) Patients TLR (+) TLR ( ) P Patient characteristics n = 7 n = 10 Age, years ± ± Male, n (%) 5 (71.4%) 7 (70.0%) Body mass index, (kg/m 2 ) ± ± Hypertension, n (%) 6 (85.7%) 7 (70.0%) Diabetes, n (%) 6 (85.7%) 7 (70.0%) Insulin treated diabetes, n (%) 5 (71.4%) 1 (10.0%) Dyslipidemia, n (%) 6 (85.7%) 10 (100.0%) Hemodialysis, n (%) 3 (42.9%) 0 (0%) Chronic kidney disease ( Grade 3a), n (%) 5 (71.4%) 6 (60.0%) Current smoking, n (%) 4 (57.1%) 0 (0.0%) Prior myocardial infarction, n (%) 2 (28.6%) 5 (50.0%) Prior stroke, n (%) 3 (42.9%) 2 (20.0%) Peripheral vessel disease, n (%) 3 (42.9%) 4 (40.0%) Previous PCI, n (%) 3 (42.9%) 6 (60.0%) Diagnosis, n (%) Stable coronary artery disease 4 (57.1%) 7 (70.0%) Silent myocardial ischemia 0 (0.0%) 1 (10.0%) Unstable angina 2 (28.6%) 0 (0.0%) STEMI 1 (14.3%) 0 (0.0%) NSTEMI 0 (0.0%) 2 (20.0%) Recent myocardial infarction 0 (0.0%) 0 (0.0%) LVEF < 30%, n (%) 1 (14.3%) 1 (10.0%) Multivessel disease treatment, n (%) 0 (0.0%) 3 (30.0%) Procedural characteristics Number of stent, n 1.86 ± ± IVUS guidance, n (%) 7 (100.0%) 9 (90.0%) OCT guidance, n (%) 0 (0.0%) 1 (10.0%) Distal protection, n (%) 1 (14.3%) 0 (0.0%) Thrombectomy, n (%) 0 (0.0%) 1 (10.0%) IABP support, n (%) 1 (14.3%) 0 (10.0%) Lesion characteristics n = 8 n = 16 Target vessel, n (%) RCA 4 (50.0%) 4 (25.0%) LAD 0 (0.0%) 2 (12.5%) LCX 0 (0.0%) 3 (18.8%) LMT 1 (12.5%) 2 (12.5%) SVG 3 (37.5%) 5 (31.3%) Due to SVG failure, n (%) 6 (75.0%) 13 (81.3%) Pre TIMI grade, n (%) (25.0%) 4 (25.0%) 1 0 (0.0%) 0 (0.0%) 2 0 (0.0%) 6 (37.5%) 3 6 (75.0%) 6 (37.5%) ACC/AHA lesion classification, n (%) A 0 (0.0%) 1 (6.25%) B1 1 (12.5%) 3 (18.8%) B2 1 (12.5%) 2 (12.5%) C 6 (75.0%) 10 (62.5%) In-stent restenosis, n (%) 2 (25.0%) 5 (31.3%) Lesion length, n (%) < 10 mm 2 (25.0%) 9 (56.25%) 10~20 mm 4 (50.0%) 4 (25.0%) > 20 mm 2 (25.0%) 3 (18.8%) Thrombus, n (%) 0 (0.0%) 1 (6.25%) Eccentric, n (%) 1 (12.5%) 2 (12.5%) Angulated, n (%) < 45 degrees 6 (75.0%) 16 (100.0%) 45~90 degrees 1 (12.5%) 0 (0.0%) > 90 degrees 1 (12.5%) 0 (0.0%) Calcification, n (%) None or mild 6 (75.0%) 11 (82.9%) Moderate 0 (0.0%) 3 (18.8%) Severe 2 (25.0%) 2 (12.5%) Ulceration, n (%) 0 (0.0%) 1 (6.25%) Tortuosity, n (%) 0.018

8 Vol 57 No 2 EVEROLIMUS-ELUTING STENT IMPLANTATION AFTER CABG 165 None or mild 5 (62.5%) 15 (93.8%) Moderate 3 (37.5%) 0 (0.0%) Severe 0 (0.0%) 1 (6.3%) Ostial, n (%) 2 (25.0%) 2 (12.5%) Bifurcation, n (%) 2 (25.0%) 5 (31.3%) Medina 1,1,1, n (%) 1 (12.5%) 1 (6.3%) Chronic total occlusion, n (%) 2 (25.0%) 3 (18.8%) Aneurysm, n (%) 0 (0.0%) 1 (6.3%) TLR indicates target lesion revascularization; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction; NSTEMI, non ST-elevation myocardial infarction; LVEF, left ventricular ejection fraction; IVUS, intravascular ultrasound; OCT, optical coherence tomography; IABP, intra-aortic balloon pumping; RCA, right coronary artery; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; LM, left main coronary artery; SVG, saphenous vein graft; TIMI, thrombolysis in myocardial infarction; and ACC/AHA, American College of Cardiology/American Heart Association. beyond 1 year after stent implantation ) The data from our landmark analysis indicate a higher late restenosis rate, probably because of neoatherosclerosis, after EES implantation in patients with a history of CABG. Previous reports have demonstrated a poorer clinical outcome after PCI for patients with a history of CABG. Sabik, et al reported that younger age, higher triglycerides, lower highdensity lipoprotein, diabetes, and more extensive coronary artery disease were risk factors for revascularization after CABG surgery. 14) The present study supports this data by showing a higher rate of insulin-treated diabetes and dyslipidemia in the group with a previous history of CABG surgery. Our study showed that the major reason for revascularization in patients with a history of CABG is SVG failure. SVG disease has been identified as a powerful risk factor for restenosis after PCI. Despite the low incidence of clinical events after EES implantation, 3,4) SVG disease remains a risk factor for restenosis. Pokala, et al reported that second generation DES (69% EES) implantation failed to improve the 2-year followup TLR rate for SVG disease. 15) According to Sen, et al, revascularization rates were higher after second generation DES (50% EES) implantation for patients with a previous history of CABG because of repeated revascularizations after PCI of degenerated SVG. 7) Our data support findings that even second generation DES cannot eliminate revascularization after PCI in patients with a history of CABG. Although a previous investigation has shown that clinical event rates were similar among second generation DES, 16) differences among the types of second generation DES have been pathologically demonstrated. 17) Our investigation evaluated only patients who underwent EES implantation and confirmed poor outcomes in those with a history of CABG. In our report, the majority of patients who had a history of CABG underwent PCI due to SVG failure even when the target lesion of PCI was SVG in only approximately 30% of the lesions. Furthermore, our data showed that a prior CABG was a risk factor for TLR and MACE irrespective of whether or not the target lesion was located at the SVG. The incidence of TLR post-pci (native vessel) in the prior CABG (+) group appeared to be higher than that of a previous report. 7) Our data showed that the patient subset with native coronary artery PCI in the prior CABG (+) group included more patients with diabetes and insulin-treated diabetes, which are recognized as risk factors of restenosis after EES implantation. 6) According to a previous paper that specifically enrolled high-risk (eg, diabetes) subsets, CABG showed a lower clinical event rate compared with PCI. 18,19) Based on this, a poor clinical outcome after PCI for patients with a history of CABG may be a matter of course. When revascularization is required for patients with a history of CABG, various options other than PCI should be considered. Further investigations to test various interventions (eg, re-cabg, optimal medical therapy alone) for this highrisk subset are warranted. In the present study, current smoking was more frequently observed in patients who required TLR, in particular, among the patients with a previous history of CABG. Some previous reports have shown that current smoking was not necessarily a risk factor for clinical events after PCI in the BMS era. 20,21) However, recent papers on interventional cardiology written after the emergence of DES showed that current smoking is an independent risk factor for stent thrombosis 22) and neoatherosclerosis, 23) which can be a cause of late catch-up restenosis after DES implantation. Our results strongly support comprehensive risk control including patient education as a means of improving clinical outcomes in high risk subsets even in the contemporary DES-PCI era. Limitation of the study: Selection and misclassification biases and the possibility of type 2 errors cannot be ruled out in this retrospective study because it was conducted in a single center with a limited sample size compared with previous studies. Conclusion: This study revealed that a history of CABG is a risk factor for TLR after EES implantation. The major reason for PCI after CABG was SVG failure; both native vessel and SVG PCI groups showed poor outcomes. Further investigations may be warranted to determine which interventions are most effective in this high-risk subset. References 1. Stefanini GG, Holmes DR Jr. Drug-eluting coronary-artery stents. N Engl J Med 2013; 368: (Review) 2. Takada K, Ishikawa S, Yokoyama N, Hosogoe N, Isshiki T. 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