CLINICAL STUDY. From the 1 Cardiovascular Center, Seoul National University Hospital, Seoul,

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1 CLINICAL STUDY The Effect of Cilostazol on the Angiographic Outcome of Drug-Eluting Coronary Stents Angiographic Analysis of the CILON-T (Influence of CILostazol-Based Triple Antiplatelet Therapy ON Ischemi Complication after Drug-Eluting StenT Implantation) Trial Jung-Won Suh, 1,2 MD, Seung-Pyo Lee, 1 MD, KyungWoo Park, 1 MD, Hyun-Jae Kang, 1 MD, Bon-Kwon Koo, 1 MD, Young-Seok Cho, 2 MD, Tae-Jin Youn, 2 MD, In-Ho Chae, 2 MD, Dong-Ju Choi, 2 MD, Seung-Woon Rha, 3 MD, Jang-Ho Bae, 4 MD, Taek-Geun Kwon, 4 MD, Jang-Whan Bae, 5 MD, Myeong-Chan Cho, 5 MD and Hyo-Soo Kim, 1 MD Summary It is not clear if anti-restonotic effect of cilostazol is consistent for different types of drug-eluting stents (DES). The purpose of this study was to compare the anti-proliferative effect of cilostazol between DAT and TAT with consideration of confounding influences of DES type. Nine hundred and fifteen patients were randomized to either dual antiplatelet therapy (DAT; aspirin and clopidogrel) or triple antiplatelet therapy (TAT; aspirin, clopidogrel, and cilostazol) in the previous CILON-T trial. After excluding 70 patients who received both or neither stents, we analyzed 845 patients who received exclusively PES or ZES, and compared in-stent late loss at 6 months between both antiplatelet regimens (DAT versus TAT). Baseline angiographic and clinical characteristics were similar between the DAT (656 lesions in 425 patients) and the TAT group (600 lesions in 420 patients). The 6-month follow-up angiography was completed in 745 patients (88.2%). Quantitative coronary angiography showed that TAT significantly reduced in-stent late loss (DAT 0.62 ± 0.62 mm versus TAT 0.54 ± 0.49 mm, P = 0.015). Stent type, diabetes or lesion length did not interact with difference of late loss. However, reduction of late loss by cilostazol did not lead to a significant reduction in the rate of target lesion revascularization (TLR) (DAT 7.8% versus TAT 6.9%, P = 0.69) due to a nonlinear relationship found between late loss and TLR. The TAT group showed less in-stent late loss as compared to the DAT group. This was consistently observed regardless of DES type, lesion length, or diabetic status. However, reduction of late loss by cilostazol did not lead to a significant reduction in TLR. (Int Heart J 2017; 58: ) Key words: Cilostazol, Paclitaxel-eluting stent, Zotarolimus-eluting stent, Restenosis C ilostazol is a selective phosphodiesterase (PDE) 3 inhibitor that is commonly prescribed in patients with peripheral artery disease. It reduces restenosis of bare metal stents and drugeluting stents (DES) after percutaneous coronary intervention (PCI) as a result of its anti-proliferative effect. 1) It also intensified platelet inhibition in patients who showed high post-treatment platelet reactivity despite conventional dual antiplatelet therapy (DAPT). 2-4) Previous studies showed the benefit of cilostazol in specific subgroups, such as diabetic patients and those with long coronary lesions. 5-7) However, it is not clear if these results can be extrapolated to the general population. The CILON-T trial was a prospective, randomized trial that compared the efficacy of dual antiplatelet therapy (DAT) (i.e., aspirin, clopidogrel) and triple antiplatelet therapy (TAT) (i.e., aspirin, clopidogrel, and cilostazol) in patients who underwent drug-eluting stent (DES) implan- From the 1 Cardiovascular Center, Seoul National University Hospital, Seoul, 2 Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, 3 Cardiovascular Center, Korea University Guro Hospital, Seoul, 4 Heart Center, Konyang University Hospital, Daejon and 5 Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea. This study was supported by a grant from the SNUBH Research Fund ( ) and a grant from the Clinical Research Center for Ischemic Heart Disease, Seoul, Republic of Korea (0412-CR ). Address for correspondence: Hyo-Soo Kim, MD, Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital, 101 Daehang-no, Chongno-gu, Seoul , Korea. hyosoo@snu.ac.kr Received for publication July 18, Revised and accepted January 13, Released in advance online on J-STAGE November 8, doi: /ihj All rights reserved by the International Heart Journal Association. 853

2 854 Suh, ET AL IntHeartJ November patients eligible for trial Withdrawal at patient request (n =5) Withdrawal at clinician s judgment (n = 33) Failed percutaneous coronary intervention (n =7) 915 patients enrolled for final analysis Neither PES nor ZES (n = 64) Both PES and ZES (n =6) DAT (n = 425) TAT (n = 420) PES 334 lesions/218 patients ZES 322 lesions/207 patients PES 327 lesions/230 patients ZES 273 lesions/190 patients Follow-up angiography at 6 months (n = 745, 88.2%) PES 278 lesions/183 patients ZES 294 lesions/189patients PES 293 lesions/205 patients ZES 247 lesions/168 patients Figure 1. Study flow. tation. 2,8) In this study, we analyzed the effect of cilostazol on restenosis after DES implantation by using angiographic analysis to compare late loss in patients enrolled in the CILON-T trial. Analyses were stratified by the type of antiplatelet regimen (DAT versus TAT) and the type of DES, the paclitaxel-eluting stent (PES, TAXUS Express2, Boston Scientific Corporation) versus the zotarolimuseluting stent (ZES, Endeavor Sprint, Medtronic). Methods Patients: The CILON-T trial was a prospective, openlabel randomized trial that took place at five centers in South Korea: the Seoul National University Hospital, Seoul National University Bundang Hospital, Korea Guro Hospital, Konyang University Hospital, and Chungbuk National University Hospital. Patients were enrolled between September 2006 and June ,8) All patients gave written informed consent, and the institutional review boards at the five centers approved this study. The design of the CILON-T trial has been published elsewhere, and the full protocol is registered at (NCT ). 8) Briefly, a total of 960 consecutive patients who were implanted with a DES were randomized into two groups to receive either DAT (aspirin and clopidogrel) or TAT (aspirin, clopidogrel, and cilostazol) (Figure 1). Among the initially randomized patients, five patients withdrew consent, seven patients failed to implant DES for the target lesion, and 33 patients withdrew from the study by the duty physician s judgment for several reasons, which included high risk of significant bleeding in the near future, and a planned operation that needed antiplatelet agent modification or discontinuation. In the present study, we analyzed patients (n = 845) treated with either the PES or the ZES after excluding 70 patients who were treated with both stents (n =6)orneither stent (n = 64). In the DAT group, PESs were implanted at 334 lesions in 218 patients whereas ZESs were implanted at 322 lesions in 207 patients. In the TAT group, PESs were implanted at 327 lesions in 230 patients, whereas ZESs were implanted at 273 lesions in 190 patients. Follow-up angiography was done in 745 patients (88.2%; DAT n = 372, TAT n = 373) 6 months after stent implantation. Study endpoints and clinical follow-up: The primary endpoint of this study was in-stent late loss at 6 months. The secondary endpoints included in-segment late loss and restenosis rate (diameter stenosis > 50%), target lesion revascularization (TLR), and the occurrence of a major adverse cardiovascular event (MACE), including cardiac death, a nonfatal myocardial infarction, clinically driven TLR, and ischemic stroke at 6 months. Other secondary endpoints were all-cause death and stent thrombosis at 6 months. Safety assessment included bleeding complications according to the Thrombolysis In Myocardial Infarction (TIMI) criteria during the treatment period. 9) The cause of death was regarded as cardiovascular unless there was documented evidence for a clear, noncardiovascular cause. Myocardial infarction (MI) was defined as a creatinine kinase myocardial band > 3 times

3 IntHeartJ November 2017 CILOSTAZOL AND DRUG-ELUTING STENT RESTENOSIS 855 upper limit of normal. Ischemic stroke was defined as a new focal neurologic deficit of vascular origin lasting at least 24 hours that was proven to be non-hemorrhagic by either computed tomography or magnetic resonance imaging scanning. TLR was considered clinically driven when it was associated with typical symptoms upon clinical assessment, typical signs during the stress test, or > 70% stenosis on angiographic follow-up. Stent thrombosis was defined as any of the following: angiographic documentation of occlusion of the target lesion associated with an acute ischemic event, irrespective of the presence of visible thrombi on the angiograph, unexplained sudden death, and MI not clearly relevant to another coronary lesion. Follow-up: Repeat coronary angiography was performed at 6 months, or earlier if indicated. Clinical follow-up visits were scheduled 1, 3, 6, and 12 months after the procedure. The investigators followed the patients, either by office visit or by telephone as necessary. Drug compliance and adverse events were assessed during each visit for clinical follow-up. QCA analysis: Pre-procedure, post-procedure, and follow-up angiograms obtained after intracoronary nitroglycerin administration were submitted to the core analysis center (Seoul National University Hospital, Seoul, Korea). Digital angiograms were analyzed using an automated edge detection system (CASS II, Pie Medical, Maastricht, Netherlands). Quantitative coronary angiographic measurements were obtained both in-stent and insegment (stented segment and margins 5 mm proximal and distal to the stent). In-segment late loss was calculated by using the maximal regional late loss method. 10,11) Statistical analysis: Analysis of the two groups (DAT and TAT) was performed according to the intention-to-treat principle. Continuous variables are presented as the mean ± standard deviation. Means were compared using Student s unpaired t-test. Categorical variables are presented as numbers or percentages and were compared using either Chi-square Analysis or Fisher s Exact Test. A general linear model (analysis of covariance; ANCOVA) was applied to quantify the impact of cilostazol on late loss while controlling the effect of statin type. Multiple linear regression and logistic regression were used to assess the effect of DES on each outcome variable. Prespecified subgroup analysis per stent type, lesion length, or diabetic status was performed to compare the primary endpoint between the two groups by using a linear regression method. A P-value < 0.05 was considered statistically significant. A receiver operating characteristic (ROC) curve analysis was used to determine if in-stent late loss differed between patients with and without TLR after PCI. 12,13) Results Baseline characteristics: There were no significant differences between the DAT and TAT groups for the baseline clinical characteristics except for the prescription rate of angiotensin II receptor blockers at discharge after the index procedure (Table I). Angiographic outcomes: The two groups had similar baseline and post-procedural QCA characteristics (Table II). Follow-up angiography was performed in 88.8% of individuals from the DAT group and in 87.5% of individuals from the TAT group (P = 0.61) (Table III). At 6 months, TAT significantly reduced in-stent late loss (0.62 ± 0.51 mm DAT versus 0.54 ± 0.49 mm TAT, P = 0.015) and marginally reduced in-segment late loss (0.40 ± 0.49 mm DAT versus 0.35 ± 0.47 mm TAT, P = 0.10). There was a significant difference in the in-stent late loss between the DAT and the TAT group after controlling the effect of stent type (0.615 [ ] mm versus [ mm]; P = 0.046). Thus, the instent (P = 0.016) and in-segment minimum lumen diameters were larger in the TAT group than in the DAT group (P = 0.094). Target lesion revascularization was performed in 62 patients (DAT 33 patients (7.8%) versus TAT 29 patients (6.9%), P = 0.69) of 103 lesions (DAT 57 lesions (8.7%) versus TAT 46 lesions (7.7%, P = 0.54)). In the analysis of the PES and the ZES, the trend of late loss reduction by cilostazol was consistently observed for both the PES (0.53 ± 0.49 mm in DAT versus 0.48 ± 0.45 mm in TAT, P = 0.22) and the ZES (0.70 ± 0.52 mm in DAT versus 0.62 ± 0.51 mm in TAT, P = 0.075). The data from the linear regression analysis using antiplatelet therapy group (DAT versus TAT), stent type, diabetic status, and lesion length as covariates showed that TAT was significantly associated with decreased late loss, which was independent of stent type, diabetic status, or lesion length compared to DAT (Δ in-stent late loss: DAT- TAT, 95% CI = , P = 0.015). Prespecified subgroup analysis demonstrated that the difference in in-stent late loss between the two groups (DAT versus TAT) did not interact with the type of DES (PES versus ZES, P = 0.62), diabetic status (P = 0.68), or lesion length (P = 0.32) (Figure 2). Association between in-stent late loss and TLR: Among patients who underwent TLR, no difference in late loss was detected between the DAT group and the TAT group (1.40 ± 0.76 mm DAT versus 1.33 ± 0.70 mm TAT, P = 0.68). In the ROC curve analysis, in-stent late loss was able to distinguish patients with TLR from those without (AUC = 0.92, 95% confidence interval , P < ). A late loss of 1.13 mm was identified as the optimal cutoff value to predict TLR, providing a sensitivity of 83.3%, a specificity of 92.1%, a positive predictive value of 40.3%, and a negative predictive value of 98.8%. Figure 3 represents the actual plots of in-stent late loss for all lesions and lesions undergoing TLR in both the DAT and TAT groups. The distribution of late loss was down-shifted in the TAT group, more than in the DAT group. However, both groups had a similar number of patients showing greater late loss than the cutoff value, 1.13 mm (14.0% in the DAT group versus 10.9% in the TAT group, P = 0.18), leading to no difference in the TLR rates. When we analyzed the cumulative incidence of TLR as defined by increments of in-stent or in-segment late loss (Figure 4A, B), the probability of TLR sharply increased at the point of late loss around 1.5 mm in both the DAT and TAT groups. Clinical and angiographic predictors of TLR: The significant predictors for TLR were diabetes mellitus, current

4 856 Suh, ET AL IntHeartJ November 2017 Table I. Baseline Clinical Characteristics DAT (n = 425) TAT (n = 420) P Age, years 62.9 ± ± Male, n (%) 297 (70.0) 287 (69.4) 0.46 BMI, kg/m ± ± Medical history, n (%) Hypertension 286 (67.3) 270 (64.3) 0.38 Diabetes mellitus 135 (31.8) 151 (36.0) 0.22 Dyslipidemia 162 (38.1) 183 (43.6) 0.11 PCI 35 (8.2) 29 (6.9) 0.52 CABG 11 (2.6) 8 (1.9) 0.64 Current smoker, n (%) 98 (23.1) 103 (24.5) 0.55 Acute coronary syndrome, n (%) 225 (52.9) 206 (49.0) 0.61 Laboratory results Hematocrit, % 40.0 ± ± Total cholesterol, mg/dl ± ± Triglyceride, mg/dl ± ± LDL, mg/dl ± ± HDL, mg/dl 43.7 ± ± Creatinine, mg/dl 1.05 ± ± Medication at discharge Statin, n (%) 0.33 Atorvastatin 214 (50.4) 217 (51.7) Rosuvatatin 207 (48.7) 201 (47.9) Beta-blocker, n (%) 221 (52.7) 215 (51.8) 0.84 ACE inhibitor, n (%) 108 (25.8) 96 (23.1) 0.38 ARB, n (%) 91 (21.7) 66 (15.9) 0.03 Calcium channel blocker, n (%) 117 (27.9) 105 (25.3) 0.43 Nitrate, n (%) 174 (41.5) 161 (38.8) 0.44 Proton pump inhibitor, n (%) 8 (1.9) 11 (2.7) 0.50 DAT indicates dual antiplatelet therapy; TAT, triple antiplatelet therapy; BMI, body mass index; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft; LDL, low density lipoprotein; HDL, high density lipoprotein; ACE, angiotensin-converting enzyme; and ARB, angiotensin II receptor blocker. Table II. Baseline Angiographic Characteristics DAT (n = 656 lesions) TAT (n = 598 lesions) P Involved coronary artery 0.06 Left main, n (%) 9 (1.4) 11 (1.8) Left anterior descending, n (%) 284 (43.3) 275 (46.0) Left circumflex, n (%) 165 (25.2) 171 (28.6) Right coronary 198 (30.2) 141 (23.6) ACC/AHA type B2/C, % Bifurcations, % Ostial lesions, % Calcified lesions, % Thrombotic lesion, % QCA Before procedure Reference diameter, mm 2.91 ± ± Minimal luminal diameter, mm 0.82 ± ± Lesion length, mm 22.7 ± ± After procedure MLD, in-segment 2.23 ± ± MLD, in-stent 2.55 ± ± DAT, dual antiplatelet therapy; TAT, triple antiplatelet therapy; QCA, quantitative coronary angiography; and MLD, minimal luminal diameter. smoking, lesion length, and ZES, based on the multivariate analysis, which included clinical factors (i.e., age 70 years, sex, diabetes mellitus, smoking status, and TAT versus DAT), as well as angiographic parameters, including PES versus ZES, lesion length, and residual stenosis after stenting (Table IV). TAT, as compared to DAT, was not a

5 IntHeartJ November 2017 CILOSTAZOL AND DRUG-ELUTING STENT RESTENOSIS 857 Table III. Follow-Up Quantitative Coronary Angiography DAT (n = 572 lesions) TAT (n = 540 lesions) P Reference diameter, mm In-segment 2.72 ± ± In-stent 2.78 ± ± MLD, mm In-segment 1.84 ± ± In-stent 1.94 ± ± Late loss, mm In-segment 0.40 ± ± In-stent 0.62 ± ± Diameter stenosis, % In-segment 17.8 ± ± In-stent 14.4 ± ± MLD, minimal luminal diameter. Mean (95% CI) In-stent late loss P P for interaction Overall ( ) Stent type 0.62 PES ( ) 0.22 ZES ( ) DM 0.68 DM ( ) 0.25 Non-DM ( ) Lesion length 0.32 < 28mm ( ) mm ( ) mm mm 0.2mm DAT better TAT better Figure 2. Difference in in-stent late loss (Δ in-stent late loss: DAT-TAT) between the dual and triple antiplatelet therapy groups by clinical and angiographic characteristics. significant prognostic factor in the analysis (OR = 0.86, 95% CI = , P = 0.54). Clinical and safety outcomes: Thirty-one patients (7.4%) in the TAT group stopped cilostazol due to side effects, such as headache, palpitation, rash or gastrointestinal side effects. The frequency of MACE did not differ between the DAT and TAT groups (DAT 8.9% versus TAT 8.1%, P = 0.71) at the 6-month follow-up. There were also no differences in bleeding complications between the two groups. Table V summarizes the clinical outcomes for the DAT and TAT groups. Discussion In the present analysis, we found that the TAT failed to reduce TLR, although it significantly reduced in-stent late loss when compared to DAT for those with either a PES or a ZES. We also identified several risk factors that could predict TLR at 6 months after PCI. Antirestenotic effect of cilostazol: Previous studies showed that the antirestenotic effect of cilostazol was consistent both for bare metal stents and DESs. In the CREST trial, treatment with cilostazol reduced in-stent late loss by approximately 14% compared to placebo (0.91 ± 0.60 mm versus 1.06 ± 0.69 mm, P = 0.01) in patients implanted with bare metal stents. It also signifi-

6 858 Suh, ET AL IntHeartJ November 2017 cantly reduced the in-stent binary restenosis rate (20.85% versus 31.44%, P = 0.01). 1) During the DES era, cilostazol therapy achieved an approximate 18% reduction in instent late loss compared to placebo in patients implanted with a ZES (0.56 ± 0.55 mm versus 0.68 ± 0.59 mm, P = 0.045). However, it was not associated with a decreased rate of target vessel revascularization (16% versus 16%, P = 0.90). 14) Figure 3. Distribution of in-stent late loss stratified per antiplatelet strategy. TAT indicates all the patients who received triple antiplatelet therapy; TLR (+) TAT, the patients who underwent target lesion revascularization (TLR) and received TAT; DAT, all the patients who received dual antiplatelet therapy; and TLR (+) DAT: the patients who underwent TLR and received DAT. Discrepancy between late loss and TLR: This study showed that there was an association between the degree of late loss and TLR and that a late loss of 1.13 mm was identified as the optimal cutoff value to predict TLR. The distribution of late loss was down-shifted more in the TAT group than in the DAT group. However, we did not find that greater reduction of late loss led to significantly lower TLR rates in this analysis due to the insignificant difference in the actual number of patients having larger in-stent late loss than the cutoff value (1.13 mm) between the DAT (14.0%) and TAT (10.9%) groups (P = 0.18). This means that cilostazol could not reduce the number of patients who were potential candidates for TLR. A previous study suggested that coronary stenting results in large lumens with room to accommodate up to ~0.5 to 0.65 mm of neointimal tissue (angiographic analysis segment late loss) before the likelihood of clinical restenosis exceeds 5%-10%. 10) Most of late loss reduction in the TAT group compared to the DAT group was modest, and it was seen in the relatively flat portion of the association curve between TLR and late loss, which might result in no difference in TLR between the DAT and TAT groups. In addition, the insignificant and milder reduction of insegment late loss by cilostazol may contribute to the absence of a difference in the rate of TLR between the DAT and TAT groups. The anti-proliferative effect of cilostazol in patients with high risk features: Previous studies suggested that cilostazol therapy could be beneficial in terms of resteno- Figure 4. The probability of TLR according to the increment of late loss. A: In-stent late loss, B: In-segment late loss. Table IV. Clinical and Angiographic Predictors of TLR at the Six-Month Follow-Up Odds Ratio 95% confidence interval P Current smoker (versus non-smoker) ZES (versus PES) Lesion length (every increase in 1 mm) < Diabetes mellitus ZES, zotarolimus-eluting stent; and PES, paclitaxel-eluting stent.

7 IntHeartJ November 2017 CILOSTAZOL AND DRUG-ELUTING STENT RESTENOSIS 859 Table V. Clinical Outcomes at the Six-Month Follow-Up DAT (n = 425) TAT (n = 420) P MACE (%) 38 (8.9) 34 (8.1) 0.71 Cardiac death 0 3 (0.7) 0.25 Nonfatal MI 3 (0.7) 3 (0.7) 1.0 Ischemic stroke 5 (1.2) 5 (1.2) 1.0 TLR 33 (7.8) 29 (6.9) 0.69 Bleeding events (%) 0.51 TIMI criteria, major 1 (0.2) 2 (0.5) TIMI criteria, minor 1 (0.2) 0 MACE, major adverse cardiovascular event; MI, myocardial infarction; TLR, target lesion revascularization; and TIMI, thrombolysis in myocardial infarction sis, especially in patients with high-risk features, such as diabetes mellitus or long lesions. 5-7) However, the difference in in-stent late loss between the two groups did not interact with the type of DES (PES versus ZES), diabetic status, or lesion length in this study. This suggests that the anti-proliferative effect of cilostazol is not influenced by specific clinical or angiographic characteristics. Risk factors of TLR in the 1st generation of DES: Multivariate analysis confirmed that smoking, the use of ZES (versus PES), lesion length, and diabetes mellitus were predictors of TLR. The control of classic risk factors and the selection of DESs that have good angiographic profiles may be better for preventing TLR than additional pharmacologic intervention. If we consider common side effects, such as headache, gastrointestinal symptom, palpitation and tachycardia, which are not tolerable to a considerable number of patients, 15,16) the addition of cilostazol for the purpose of preventing target lesion revascularization should be reserved. Study limitations: First, this study is a subgroup analysis of a randomized, controlled trial although the analysis was prespecified. Second, the number of patients was relatively small for the comparison of clinical outcomes. The reduction of late loss by cilostazol was consistently observed regardless of stent type, diabetic status, or lesion length. The actual distribution of late loss in all lesions was down-shifted in the TAT group more than in the DAT group; thus, we could acknowledge the anti-proliferative effect of cilostazol. A study including a larger numbers of patients may enable us to translate sensitive variables, like difference in late loss, into less sensitive variables, like difference in clinical outcome. Third, only two types of the first generation DESs were compared in this study. Conclusion Cilostazol has a modest, consistent anti-proliferative effect, regardless of the type of DES, lesion length, or diabetic status. However, such an anti-proliferative effect does not lead to a significant reduction in the rate of TLR, due to the nonlinear relationship between angiographic late loss and TLR. Acknowledgment The authors appreciate statistical advice of Dr. Si- Hyuck Kang and Dr. Yun Gi Kim. We also thank Ms. Tae-Eun Kim (research coordinator), Mr. Jiyeob Lee (senior cardiovascular technologist), Ms. Sunyoung Yoo (QCA researcher) and Ms. Eunjung Park (QCA researcher) for their cordial support. Disclosures Conflicts of interest: None. References 1. Douglas JS Jr, Holmes DR Jr, Kereiakes DJ, et al; Cilostazol for Restenosis Trial (CREST) Investigators. Coronary stent restenosis in patients treated with cilostazol. Circulation 2005; 112: Suh JW, Lee SP, Park KW, et al. Multicenter randomized trial evaluating the efficacy of cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease: results of the CILON-T (influence of CILostazolbased triple antiplatelet therapy ON ischemic complication after drug-eluting stent implantation) trial. J Am Coll Cardiol 2011; 57: Jeong YH, Lee SW, Choi BR, et al. Randomized comparison of adjunctive cilostazol versus high maintenance dose clopidogrel in patients with high post-treatment platelet reactivity: results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With Clopidogrel Resistance) randomized study. J Am Coll Cardiol 2009; 53: Fu Q, Yokoyama N, Takada K, Ishikawa S, Isshiki T. Comparison of platelet P2Y(12) ADP receptor-mediated pathway in triple versus dual antiplatelet therapy as assessed by VASPphosphorylation in Japanese patients undergoing coronary stenting. Int Heart J 2010; 51: Lee SW, Park SW, Kim YH, et al. Drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients withdiabetes mellitus the DECLARE-DIABETES Trial (A Randomized Comparison of Triple Antiplatelet Therapy with Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetic Patients). J Am Coll Cardiol 2008; 51: Lee SW, Park SW, Kim YH, et al. 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