Title: Comparison of Outcomes After Percutaneous Coronary Intervention for Chronic Total Occlusion Using Everolimus- Versus Sirolimus- Versus Paclitaxel-Eluting Stents (from the Korean National Registry of Chronic Total Occlusion Intervention)
Abstract: For the treatment of chronic total occlusion (CTO), the efficacy and safety of the everolimus-eluting stent (EES) remain less well defined. Also, there are limited data for the predictors of outcome after CTO intervention. The purpose of this study was to compare clinical outcomes of the EES with the first-generation drug-eluting stent (DES) in CTO intervention and to investigate the predictors of clinical outcome. The Korean National Registry of CTO Intervention is a retrospective cohort of 26 centers from the past 5 years. The primary end point was major adverse cardiovascular events (MACE) defined as a composite of cardiac death, nonfatal myocardial infarction, and target lesion revascularization. Of the 1,754 all-comer patients, 1,509 patients (EES 311, sirolimus-eluting stent [SES] 642, paclitaxel-eluting stent 556) were finally analyzed after excluding 245 patients (mixed DESs in 46 and follow-up loss in 199). In the inverse probability weighting–adjusted population, the 1-year MACE rate of the EES was comparable with that of the SES (5.8% vs 3.4%, p = 0.796) and the paclitaxel-eluting stent (5.8% vs 6.9%, p = 0.740). Each component of MACE was also comparable among the 3 stents. Importantly, the independent predictors of MACE were diabetes mellitus, previous congestive heart failure, and left circumflex CTO. In conclusion, for the first time in the largest CTO cohort, the EES showed good 1-year clinical outcomes that were comparable with the SES. Independent predictors of MACE after CTO intervention were clinical factors (diabetes and congestive heart failure) and lesion location. For the treatment of chronic total occlusion (CTO), the efficacy and safety of the everolimus-eluting stent (EES) remain less well defined. Also, there are limited data for the predictors of outcome after CTO intervention. The purpose of this study was to compare clinical outcomes of the EES with the first-generation drug-eluting stent (DES) in CTO intervention and to investigate the predictors of clinical outcome. The Korean National Registry of CTO Intervention is a retrospective cohort of 26 centers from the past 5 years. The primary end point was major adverse cardiovascular events (MACE) defined as a composite of cardiac death, nonfatal myocardial infarction, and target lesion revascularization. Of the 1,754 all-comer patients, 1,509 patients (EES 311, sirolimus-eluting stent [SES] 642, paclitaxel-eluting stent 556) were finally analyzed after excluding 245 patients (mixed DESs in 46 and follow-up loss in 199). In the inverse probability weighting–adjusted population, the 1-year MACE rate of the EES was comparable with that of the SES (5.8% vs 3.4%, p = 0.796) and the paclitaxel-eluting stent (5.8% vs 6.9%, p = 0.740). Each component of MACE was also comparable among the 3 stents. Importantly, the independent predictors of MACE were diabetes mellitus, previous congestive heart failure, and left circumflex CTO. In conclusion, for the first time in the largest CTO cohort, the EES showed good 1-year clinical outcomes that were comparable with the SES. Independent predictors of MACE after CTO intervention were clinical factors (diabetes and congestive heart failure) and lesion location. For the treatment of de novo coronary lesions in recent large trials, the second-generation everolimus-eluting stent (EES) has been found to be noninferior to the sirolimus-eluting stent (SES) and superior to the paclitaxel-eluting stent (PES), in terms of safety and efficacy.1Park K.W. Chae I.H. Lim D.S. Han K.R. Yang H.M. Lee H.Y. Kang H.J. Koo B.K. Ahn T. Yoon J.H. Jeong M.H. Hong T.J. Chung W.Y. Jo S.H. Choi Y.J. Hur S.H. Kwon H.M. Jeon D.W. Kim B.O. Park S.H. Lee N.H. Jeon H.K. Gwon H.C. Jang Y.S. Kim H.S. Everolimus-eluting versus sirolimus-eluting stents in patients undergoing percutaneous coronary intervention: the EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) randomized trial.J Am Coll Cardiol. 2011; 58: 1844-1854Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar, 2Park K.W. Kang S.H. Velders M.A. Shin D.H. Hahn S. Lim W.H. Yang H.M. Lee H.Y. Van Boven A.J. Hofma S.H. Kang H.J. Koo B.K. Oh B.H. Park Y.B. Kandzari D.E. Kim H.S. Safety and efficacy of everolimus- versus sirolimus-eluting stents: a systematic review and meta-analysis of 11 randomized trials.Am Heart J. 2013; 165: 241-250Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 3Kedhi E. Joesoef K.S. McFadden E. Wassing J. van Mieghem C. Goedhart D. Smits P.C. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial.Lancet. 2010; 375: 201-209Abstract Full Text Full Text PDF PubMed Scopus (618) Google Scholar For the treatment of chronic total occlusion (CTO), however, the efficacy and safety of the EES still remain less well defined. There have been a few studies comparing the results between 2 different first-generation DESs.4Lee S.P. Kim S.Y. Park K.W. Shin D.H. Kang H.J. Koo B.K. Suh J.W. Cho Y.S. Yeon T.J. Chae I.H. Choi D.J. Kim H.S. Long-term clinical outcome of chronic total occlusive lesions treated with drug-eluting stents: comparison of sirolimus-eluting and paclitaxel-eluting stents.Circ J. 2010; 74: 693-700Crossref PubMed Scopus (20) Google Scholar However, there is a paucity of data on the differences in clinical outcomes between the EES and the first-generation DES for the treatment of CTO lesions because the only available data were derived from a relatively small series of patients and, therefore, are not adequately powered to detect low-frequency end points.5Moreno R. Garcia E. Teles R. Rumoroso J.R. Carvalho H.C. Goicolea F.J. Moreu J. Mauri J. Sabate M. Mainar V. Patricio L. Valdes M. Fernandez Vazquez F. Sanchez-Recalde A. Galeote G. Jimenez-Valero S. Almeida M. de Sa E.L. Calvo L. Plaza I. Lopez-Sendon J.L. Martin J.L. Investigators C. Randomized comparison of sirolimus-eluting and everolimus-eluting coronary stents in the treatment of total coronary occlusions: results from the chronic coronary occlusion treated by everolimus-eluting stent randomized trial.Circ Cardiovasc Interv. 2013; 6: 21-28Crossref PubMed Scopus (57) Google Scholar, 6Almalla M. Hennings V. Marx N. Hoffmann R. Long-term clinical and angiographic outcome after treatment of chronic total occlusion with everolimus or sirolimus eluting stents.Int J Cardiol. 2012; 157: 451-452Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar, 7Valenti R. Vergara R. Migliorini A. Parodi G. Buonamici P. Cerisano G. Carrabba N. Antoniucci D. Comparison of everolimus-eluting stent with paclitaxel-eluting stent in long chronic total occlusions.Am J Cardiol. 2011; 107: 1768-1771Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Thus, we compared the clinical outcomes of the EES with the first-generation DES, represented by the SES and the PES, for the treatment of CTO lesions using the data from the Korean National Registry of CTO Intervention (K-CTO registry). Furthermore, we would like to propose the clinical predictors of poor prognosis after CTO intervention. The K-CTO registry is a retrospective cohort of 26 centers in South Korea. From January 1, 2007, to December 31, 2009, we enrolled patients treated with an SES (Cypher; Cordis Johnson & Johnson, Miami, Florida) or a PES (Taxus; Boston Scientific Corp., Natick, Massachusetts, or Pico Elite; AMG International GmbH, Raesfeld-Erle, Germany). From January 1, 2007 to December 31, 2011, we enrolled patients treated with an EES (Xience; Abbott Vascular, Santa Clara, California; or Promus; Boston Scientific Corp.). This was an all-comer analysis that included patients with stable angina, unstable angina, non–ST-segment elevation myocardial infarction (STEMI), and STEMI and those who underwent emergent percutaneous coronary intervention (PCI). This study protocol was approved by the institutional review board at each participating center and conducted according to the principals of the Declaration of Helsinki. All patients gave informed consent to participate in the study. CTO was defined as a complete coronary obstruction with Thrombolysis In Myocardial Infarction flow grade 0 with an estimated duration ≥3 months with or without visible collateral flow, whether anterograde or retrograde.8Stone G.W. Kandzari D.E. Mehran R. Colombo A. Schwartz R.S. Bailey S. Moussa I. Teirstein P.S. Dangas G. Baim D.S. Selmon M. Strauss B.H. Tamai H. Suzuki T. Mitsudo K. Katoh O. Cox D.A. Hoye A. Mintz G.S. Grube E. Cannon L.A. Reifart N.J. Reisman M. Abizaid A. Moses J.W. Leon M.B. Serruys P.W. Percutaneous recanalization of chronically occluded coronary arteries: a consensus document: part I.Circulation. 2005; 112: 2364-2372Crossref PubMed Scopus (481) Google Scholar The duration of the occlusion was determined by the interval from the last episode of acute coronary syndrome, or in patients without a history of acute coronary syndrome, from the first episode of effort angina consistent with the location of the occlusion, or by a previous coronary angiography. All occlusions were located in a native vessel. We established 2 study end points: primary and secondary end points. The primary end point was major adverse cardiovascular events (MACE) defined as a composite of cardiac death (CD), nonfatal MI, and target lesion revascularization (TLR). The secondary end points included individual components of MACE, all-cause mortality, target vessel revascularization (TVR), and stent thrombosis (ST). All deaths were considered to have been from a cardiac cause unless a noncardiac origin was definitely documented. MI was defined according to the recommendations of the ESC/ACCF/AHA/WHF task force.9Thygesen K. Alpert J.S. White H.D. Jaffe A.S. Apple F.S. Galvani M. Katus H.A. Newby L.K. Ravkilde J. Chaitman B. Clemmensen P.M. Dellborg M. Hod H. Porela P. Underwood R. Bax J.J. Beller G.A. Bonow R. Van der Wall E.E. Bassand J.P. Wijns W. Ferguson T.B. Steg P.G. Uretsky B.F. Williams D.O. Armstrong P.W. Antman E.M. Fox K.A. Hamm C.W. Ohman E.M. Simoons M.L. Poole-Wilson P.A. Gurfinkel E.P. Lopez-Sendon J.L. Pais P. Mendis S. Zhu J.R. Wallentin L.C. Fernandez-Aviles F. Fox K.M. Parkhomenko A.N. Priori S.G. Tendera M. Voipio-Pulkki L.M. Vahanian A. Camm A.J. De Caterina R. Dean V. Dickstein K. Filippatos G. Funck-Brentano C. Hellemans I. Kristensen S.D. McGregor K. Sechtem U. Silber S. Widimsky P. Zamorano J.L. Morais J. Brener S. Harrington R. Morrow D. Lim M. Martinez-Rios M.A. Steinhubl S. Levine G.N. Gibler W.B. Goff D. Tubaro M. Dudek D. Al-Attar N. Universal definition of myocardial infarction.Circulation. 2007; 116: 2634-2653Crossref PubMed Scopus (2183) Google Scholar TLR was defined as any repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis of the target lesion. TVR was defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The presence of ST was assessed by the Academic Research Consortium definitions, and "definite or probable" categories were used to define ST.10Cutlip D.E. Windecker S. Mehran R. Boam A. Cohen D.J. van Es G.A. Steg P.G. Morel M.A. Mauri L. Vranckx P. McFadden E. Lansky A. Hamon M. Krucoff M.W. Serruys P.W. Clinical end points in coronary stent trials: a case for standardized definitions.Circulation. 2007; 115: 2344-2351Crossref PubMed Scopus (4831) Google Scholar All PCI procedures were performed using standard techniques. Various guidewires were used to cross the lesions. After pre-dilation, stents were deployed, and if necessary, adjunctive high-pressure balloon dilation was performed to achieve angiographic optimization. All patients were pretreated with aspirin and clopidogrel. Unfractionated heparin was administered either before or during the intervention to achieve adequate anticoagulation. The selection of equipment for the angioplasty, including the choice of DES, was decided by the operator during the procedure. The use of a glycoprotein IIb/IIIa inhibitor was also left to the operator's discretion. After the procedure, all patients were given aspirin (at least 100 mg/d) indefinitely and clopidogrel (75 mg/d) for at least 12 months. After index PCI, follow-ups were recommended at 1, 6, 9, and 12 months. Routine follow-up angiography was optional at 6 to 9 months. Clinical, angiographic, procedural, and outcome data were collected by independent nurses and researchers who were unaware of the purpose of the study. Patient data were retrospectively reviewed through electronic medical records. The analysis was performed in 2 parts. First, analysis and comparison of the primary and secondary end points were conducted in the whole population. Second, comparison of the primary and secondary end points was re-analyzed by an inverse probability-weighted Cox proportional hazard model as a sensitivity analysis. Baseline and angiographic characteristics among the patients treated with the SES, the EES, or the PES were compared using a 1-way analysis of variance for continuous variables and the chi-square test for categorical variables. Cumulative event curves were plotted by means of the Kaplan-Meier method, and the differences among the 3 stent groups were assessed with the log-rank test. To reduce the impact of treatment selection bias, the difference in baseline characteristics and potential confounding bias, which were inherited limitations of an observational registry based study, we performed rigorous adjustment for the differences in baseline characteristics of patients using weighted Cox proportional hazards regression models with inverse probability of treatment weighting.11Kurth T. Walker A.M. Glynn R.J. Chan K.A. Gaziano J.M. Berger K. Robins J.M. Results of multivariable logistic regression, propensity matching, propensity adjustment, and propensity-based weighting under conditions of nonuniform effect.Am J Epidemiol. 2006; 163: 262-270Crossref PubMed Scopus (557) Google Scholar, 12Cole S.R. Hernan M.A. Adjusted survival curves with inverse probability weights.Comput Methods Programs Biomed. 2004; 75: 45-49Abstract Full Text Full Text PDF PubMed Scopus (581) Google Scholar, 13Robins J.M. Hernan M.A. Brumback B. Marginal structural models and causal inference in epidemiology.Epidemiology. 2000; 11: 550-560Crossref PubMed Scopus (3575) Google Scholar In brief, propensity scores, which were the probabilities that patients received the EES, were calculated by a multiple logistic regression model, based on the 16 covariates. The adjusted variables of baseline characteristics were as follows: age (continuous), gender (men or women), hypertension (yes or no), diabetes mellitus (DM) (yes or no), smoking (current or noncurrent), dyslipidemia (yes or no), clinical indication of PCI (stable angina pectoris, unstable angina pectoris, NSTEMI, STEMI), left main (LM) disease (yes or no), number of disease vessel (1 vessel disease [VD], 2VD, and 3VD), lesion of CTO (left anterior descending [LAD], left circumflex [LC], right coronary, and LM), previous PCI (yes or no), previous coronary bypass (yes or no), previous MI (yes or no), history of congestive heart failure (CHF) (yes or no), total stent length in CTO lesion (continuous), and mean stent diameter in CTO lesion (continuous). After creating the inverse probability of treatment weighting, an inverse probability-weighted Cox proportional hazard model was fitted to compare the primary and secondary end points of the 3 groups. In addition, an inverse probability-weighted Cox proportional hazard model was used to identify independent predictors of the primary clinical outcome, MACE. Additionally, pooled analysis for MACE was done to enhance statistical power for the rare clinical events. The pooled odds ratio was calculated with the methods by DerSimonian and Laird14DerSimonian R. Laird N. Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177-188Abstract Full Text PDF PubMed Scopus (30306) Google Scholar for random effects and Mantel-Haenszel for fixed effects. Heterogeneity was measured using the Cochran Q through the chi-square test and quantified using the I2 test.15Higgins J.P. Thompson S.G. Deeks J.J. Altman D.G. Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560Crossref PubMed Scopus (42801) Google Scholar All statistical analyses were performed using SAS, version 9 (SAS Institute, Inc., Cary, North Carolina) and R programming, version 3.0.2 (The R Foundation for Statistical Computing, Vienna, Austria) using the meta-for and meta-commands. A 2-sided p value <0.05 was considered to be statistically significant. A total of 1,754 patients were successfully revascularized for their CTO lesions using an SES or PES from January 2007 to December 2009 or using an EES from January 2007 to December 2011. Of them, 1,509 patients (EES 311, SES 642, PES 556) were finally analyzed after excluding 245 patients (mixed DESs in 46 and follow-up loss in 199). Baseline characteristics of the groups are listed in Table 1. Overall baseline clinical and angiographic results were well balanced with a high proportion of DM or current smokers. There were differences among the 3 groups in terms of clinical indication of PCI, lesion of CTO, and mean stent diameter in CTO lesion.Table 1Baseline characteristics of the whole populationVariableEES(n = 311)SES(n = 642)PES(n = 556)p valueAge (years)62.3 ± 11.561.6 ± 11.062.3 ± 10.80.463Men236 (75.9%)465 (72.4%)414 (74.5%)0.486Diabetes mellitus126 (40.6%)213 (33.3%)202 (36.6%)0.081Hypertension208 (67.1%)407 (63.7%)348 (63.3%)0.494Dyslipidemia124 (40.5%)241 (38.6%)202 (36.6%)0.806Current smoker92 (32.4%)198 (32.0%)171 (35.5%)0.455Previous percutaneous coronary intervention61 (19.6%)149 (23.3%)130 (23.5%)0.362Previous coronary bypass8 (2.6%)12 (1.9%)16 (2.9%)0.513Previous myocardial infarction37 (12.0%)82 (12.9%)81 (14.6%)0.493Previous congestive heart failure22 (7.5%)48 (7.5%)42 (7.7%)0.989Clinical indication of percutaneous coronary intervention0.024 Stable angina pectoris134 (49.3%)281 (48.1%)201 (40.4%) Unstable angina pectoris89 (32.7%)217 (37.2%)209 (42.0%) non-ST-segment elevation myocardial infarction34 (12.5%)45 (7.7%)53 (10.6%) ST-segment elevation myocardial infarction15 (5.5%)41 (7.0%)35 (7.0%)Procedural characteristics No. of coronary arteries narrowed0.810- 1104 (33.5%)231 (36.2%)183 (32.9%)- 2102 (32.9%)207 (32.4%)188 (33.8%)- 3104 (33.5%)201 (31.5%)185 (33.3%) Left main disease13 (4.2%)12 (1.9%)22 (4.0%)0.054 Lesion of CTO<0.001- Left anterior descending112 (40.9%)334 (52.2%)205 (37.0%)- Left circumflex55 (20.1%)108 (16.8%)116 (20.9%)- Right105 (38.3%)196 (30.5%)230 (41.5%)- Left main2 (0.7%)4 (0.6%)3 (0.5%) Total stent length in CTO lesion (mm)40.8 ± 20.840.7 ± 20.342.9 ± 22.70.179 Mean stent diameter in CTO lesion (mm)2.89 ± 0.372.85 ± 0.292.95 ± 0.950.016CTO = chronic total occlusion; EES = everolimus-eluting stent; PES = paclitaxel-eluting stent; SES = sirolimus-eluting stent. Open table in a new tab CTO = chronic total occlusion; EES = everolimus-eluting stent; PES = paclitaxel-eluting stent; SES = sirolimus-eluting stent. The cumulative clinical outcomes of the whole population at 1 year are presented in Table 2. In the SES versus EES comparison, the rate of MACE did not differ throughout the whole population. Although, no significant differences were observed in individual components of MACE, all-cause mortality, TVR, and ST between the 2 groups, the hard end point, such as CD or MI, was numerically the lowest in the EES, whereas the soft end point, such as TLR or TVR, was numerically the lowest in the SES.Table 2Hazard ratio for clinical outcomes at 1 year (3 group comparison)Whole population analysisIPW adjusted population analysisEvent (%)HR95% CIp valueHR95% CIp valueMACEEES3.9% (12/311)1.000NANA1.000NANASES (vs. EES)3.1% (20/642)0.5890.227-1.5240.4560.7080.260-1.9280.796PES (vs. EES)6.1% (34/556)1.2220.497-3.0020.9331.4390.554-3.7310.740PES (vs. SES)2.0770.974-4.4270.0622.0310.951-4.3360.075All cause deathEES0.6% (2/311)1.000NANA1.000NANASES (vs. EES)1.4% (9/642)1.2340.182-8.3690.9911.7600.244-12.7060.871PES (vs. EES)2.2% (12/556)1.5420.217-10.7060.9391.4890.184-12.0310.957PES (vs. SES)1.2350.327-4.6630.9740.8460.222-3.2230.987CDEES0.3% (1/311)1.000NANA1.000NANASES (vs. EES)0.8% (5/642)1.4100.098-20.3580.9862.4480.114-52.6360.864PES (vs. EES)1.3% (7/556)2.0300.141-29.3000.8942.4630.106-57.6530.871PES (vs. SES)1.4390.266-7.7880.9391.0060.182-5.558>0.999MIEES0.3% (1/311)1.000NANA1.000NANASES (vs. EES)0.5% (3/642)1.0350.066-16.310>0.9990.8810.069-11.2440.999PES (vs. EES)0.7% (4/556)1.5070.096-23.7370.9791.2710.099-16.3010.994PES (vs. SES)1.4550.207-10.2260.9561.4430.210-9.8930.957TLREES3.5% (11/311)1.000NANA1.000NANASES (vs. EES)2.2%(14/642)0.4600.160-1.3180.2160.5040.166-1.5330.367PES (vs. EES)5.0% (28/556)1.1310.434-2.9480.9861.3450.493-3.6700.860PES (vs. SES)2.4591.028-5.8810.0412.6701.098-6.4900.025TVREES3.5% (11/311)1.000NANA1.000NANASES (vs. EES)2.6% (17/642)0.5370.193-1.4890.3750.6070.208-1.7730.604PES (vs. EES)5.4% (30/556)1.2450.484-3.2030.9261.5230.567-4.0880.671PES (vs. SES)2.3201.026-5.2480.0412.5101.106-5.6930.022STEES0.6% (2/311)1.000NANA1.000NANASES (vs. EES)0.3% (2/642)0.7080.038-13.1790.9890.5860.038-9.1170.954PES (vs. EES)0.4% (2/556)0.5110.017-14.9540.9510.4320.018-10.6260.897PES (vs. SES)0.7220.039-13.4420.9910.7370.040-13.5280.992CD = cardiac death; CI = confident interval; EES = everolimus-eluting stent; HR = hazard ratio; IPW = inverse probability weighting; MACE = major adverse cardiovascular events; MI = myocardial infarction; NA = not applicable; PES = paclitaxel-eluting stent; SES = sirolimus-eluting stent; ST = stent thrombosis; TLR = target lesion revascularization; TVR = target vessel revascularization. Open table in a new tab CD = cardiac death; CI = confident interval; EES = everolimus-eluting stent; HR = hazard ratio; IPW = inverse probability weighting; MACE = major adverse cardiovascular events; MI = myocardial infarction; NA = not applicable; PES = paclitaxel-eluting stent; SES = sirolimus-eluting stent; ST = stent thrombosis; TLR = target lesion revascularization; TVR = target vessel revascularization. When comparing the PES with the EES, the rate of MACE in the EES was numerically lower than in the PES; however, it did not reach statistical significance. Regarding the secondary end points, no differences were observed between the 2 groups. In the PES versus the SES comparison, the rate of MACE in the PES was higher than that in the SES with marginal significance. In addition, the PES was associated significantly higher rates of TLR and TVR compared with the SES. However, there were no differences in all-cause mortality, CD, MI, and ST between the 2 groups. To minimize allocation bias and better describe the treatment effect of different types of stents, we performed inverse probability weighting (IPW). Table 3 describes baseline characteristics of the groups balanced by IPW, which did not differ significantly among the 3 groups and were more balanced than before weighting.Table 3Inverse probability weighting adjusted baseline characteristicsVariableEES(n = 189)SES(n = 526)PES(n = 367)p valueAge (years) (± SE)61.7 ± 0.861.7 ± 0.561.7 ± 0.60.999Male71.6%73.7%73.8%0.837Diabetes mellitus33.7%35.1%34.8%0.936Hypertension65.1%64.9%64.9%0.999Dyslipidemia40.0%40.2%40.4%0.996Current smoker35.0%34.1%33.6%0.943Previous percutaneous coronary intervention21.2%20.6%21.4%0.960Previous coronary bypass2.4%2.3%2.6%0.954Previous myocardial infarction12.2%13.1%13.3%0.929Previous congestive heart failure7.0%6.5%6.5%0.973Clinical indication of percutaneous coronary intervention0.993 Stable angina pectoris43.1%45.2%45.6% Unstable angina pectoris41.2%38.4%38.3% non-ST-segment elevation myocardial infarction8.5%9.5%8.9% ST-segment elevation myocardial infarction7.2%6.8%7.2%Procedural characteristics No. of coronary arteries narrowed0.991- 136.0%34.4%34.3%- 232.9%32.9%32.6%- 336.4%32.7%33.1% LM disease2.9%3.2%3.1%0.980 Lesion of CTO>0.999- Left anterior descending44.5%46.1%46.0%- Left circumflex18.4%18.5%18.5%- Right36.4%34.9%34.9%- Left main0.7%0.5%0.5% Total stent length in CTO lesion (mm) (± SE)41.2 ± 1.540.9 ± 0.941.3 ± 1.10.949 Mean stent diameter in CTO lesion (mm) (± SE)2.88 ± 0.042.87 ± 0.022.89 ± 0.030.834CTO = chronic total occlusion; EES = everolimus-eluting stent; PES = paclitaxel-eluting stent; SE = standard error; SES = sirolimus-eluting stent. Open table in a new tab CTO = chronic total occlusion; EES = everolimus-eluting stent; PES = paclitaxel-eluting stent; SE = standard error; SES = sirolimus-eluting stent. The clinical outcomes of the patients adjusted by IPW (Table 2 and Figure 1) were concordant with the results of the whole population. Hazard of CD was the lowest in the EES and that of TLR was the lowest in the SES. In the SES versus the EES comparison, no differences were seen in the primary and secondary end points. Comparing the PES with the EES, there were also no significant differences in the primary and secondary end points. However, the rates of MACE, TLR, and TVR in the PES remained higher than that in the SES. To identify independent predictors of MACE in CTO lesions after successful PCI with a DES, inverse probability-weighted multivariable adjusted Cox regression analysis was performed. Significant independent predictors were (1) DM (hazards ration [HR] 1.955, 95% confidence interval [CI] 1.105 to 3.457, p = 0.021), (2) previous CHF (HR 2.529, 95% CI 1.1.136 to 5.631, p = 0.023), and (3) LC CTO (vs LAD CTO) (HR 2.089, 95% CI 1.030 to 4.237, p = 0.041; Table 4).Table 4Inverse probability weighted multivariable adjusted Cox regression model for independent predictors of major adverse cardiovascular eventsAdjusted HR95% CIp valueDiabetes mellitus1.9551.105-3.4570.021Previous congestive heart failure2.5291.136-5.6310.023SES (vs. EES)0.7080.301-1.6650.429PES (vs. EES)1.5090.660-3.4500.329LC CTO (vs. LAD CTO)2.0891.030-4.2370.041Right CTO (vs. LAD CTO)0.9490.475-1.8970.883LM CTO (vs. LAD CTO)6.3170.669-59.6580.108Included variables: type of stent; age; sex; diabetes mellitus; hypertension; dyslipidemia; current smoking; previous percutaneous coronary intervention; previous coronary bypass; previous myocardial infarction; previous congestive heart failure; clinical indication of percutaneous coronary intervention, disease extent; LM disease; lesion of CTO; total stent length in CTO lesion; and mean stent diameter in CTO lesion.CI = confident interval; CTO = chronic total occlusion; EES = everolimus-eluting stent; HR = hazard ratio; LAD = left anterior descending; LC = left circumflex; LM = left main; PES = paclitaxel-eluting stent; SES = sirolimus-eluting stent. Open table in a new tab Included variables: type of stent; age; sex; diabetes mellitus; hypertension; dyslipidemia; current smoking; previous percutaneous coronary intervention; previous coronary bypass; previous myocardial infarction; previous congestive heart failure; clinical indication of percutaneous coronary intervention, disease extent; LM disease; lesion of CTO; total stent length in CTO lesion; and mean stent diameter in CTO lesion. CI = confident interval; CTO = chronic total occlusion; EES = everolimus-eluting stent; HR = hazard ratio; LAD = left anterior descending; LC = left circumflex; LM = left main; PES = paclitaxel-eluting stent; SES = sirolimus-eluting stent. Subgroup analysis regarding MACE was performed according to old age (≥65 years), gender, presence of hypertension, DM, dyslipidemia, current smoking, history of PCI, history of coronary bypass, history of MI, history of CHF, presence of MI, multivessel disease, LM disease, long stenting (≥40 mm), and LAD CTO. The results in various subgroups were similar to those observed in the entire population (Figure 2). There were no significant differences in clinical outcomes between the EES and the SES or the EES and the PES, and the results were consistent across all subgroups, without any significant interaction p value. The K-CTO registry compared the second-generation EES with the first-generation SES and PES in CTO lesions. To date, this is the largest study comparing the outcomes of the first- and second-generation DES in CTO patients at 1 year. The major findings of the present analyses are (1) in all-comer CTO patients, the EES showed comparable efficacy to the SES or the PES in terms of MACE and secondary end points, such as all-cause mortality, CD, MI, TLR, and TVR; (2) the SES showed a lower rate of MACE than the PES with marginal significance, mainly because of the lower rate of TLR; (3) independent predictors of MACE after CTO intervention were DM and previous CHF, suggesting that clinical profiles are important in determining the outcomes after CTO intervention; and (4) vessel location of CTO lesion is important for MACE (the poorest outcomes in LC CTO). In CTO intervention, the DES was better than the bare-metal stent in terms of restenosis and repeat revascularization.16Hoye A. Tanabe K. Lemos P.A. Aoki J. Saia F. Arampatzis C. Degertekin M. Hofma S.H. Sianos G. McFadden E. van der Giessen W.J. Smits P.C. de Feyter P.J. van Domburg R.T. Serruys P.W. Significant reduction in restenosis after the use of sirolimus-eluting stents in the treatment of chronic total occlusions.J Am Coll Cardiol. 2004; 43: 1954-1958Abstract Full Text Full Text PDF PubMed Scopus (203) Google Scholar, 17Werner G.S. Krack A. Schwarz G. Prochnau D. Betge S. Figulla H.R. Prevention of lesion recurrence in chronic total coronary occlusions by paclitaxel-eluting stents.J Am Coll Cardiol. 2004; 44: 2301-2306Abstract Full Text