The Journal of Tehran University Heart Center Original Article Mid-Term Follow-Up of Drug-Eluting Stenting for In-Stent Restenosis: Bare-Metal Stents versus Drug- Eluting Stents Negar Faramarzi, MD, Mojtaba Salarifar, MD*, Seyed Ebrahim Kassaian, MD, FACC, Ali Mohammad Haji Zeinali, MD, Mohammad Alidoosti, MD, Hamidreza Pourhoseini, MD, Ebrahim Nematipour, MD, Mohammad Reza Mousavi, MD, Hamidreza Goodarzynejad, MD Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Received 01 March 2012; Accepted 06 August 2012 Abstract Background: Despite major advances in percutaneous coronary intervention (PCI), in-stent restenosis (ISR) remains a therapeutic challenge. We sought to compare the mid-term clinical outcomes after treatment with repeat drug-eluting stent (DES) implantation (“DES sandwich” technique) with DES placement in the bare-metal stent (DES-in-BMS) in a "real world" setting. Methods: We retrospectively identified and analyzed clinical and angiographic data on 194 patients previously treated with the DES who underwent repeat PCI for ISR with a DES or a BMS. ISR was defined, by visual assessment, as a luminal stenosis greater than 50% within the stent or within 5 mm of its edges. We recorded the occurrence of major adverse cardiac events (MACE), defined as cardiac death, non-fatal myocardial infarction, and the need for target vessel revascularization (TVR). Results: Of the 194 study participants, 130 were men (67.0%) and the mean ± SD of age was 57.0 ± 10.4 years, ranging from 37 to 80 years. In-hospital events (death and Q-wave myocardial infarction) occurred at a similar frequency in both groups. Outcomes at twelve months were also similar between the groups with cumulative clinical MACE at one-year follow-up of 9.6% and 11.3% in the DES-in-BMS and the DES-in-DES groups, respectively (p value = 0.702). Although not significant, there was a trend toward a higher TVR rate in the intra-DES ISR group as compared to the intra-BMS ISR group (0.9% BMS vs. 5.2% DES; p value = 0.16). Conclusion: Our study suggests that the outcome of the patients presenting with ISR did not seem to be different between the two groups of DES-in-DES and DES-in-BMS at one-year follow-up, except for a trend toward more frequent TVR in the DES-in-DES group. Repeat DES implantation for DES restenosis could be feasible and safe with a relatively low incidence of MACE at mid-term follow-up. J Teh Univ Heart Ctr 2013;8(1):14-20 This paper should be cited as: Faramarzi N, Salarifar M, Kassaian SE, Haji Zeinali AM, Alidoosti M, Pourhoseini H, Nematipour E, Mousavi MR, Goodarzynejad H. Mid-Term Follow-Up of Drug-Eluting Stenting for in-Stent Restenosis: Bare-Metal Stents versus Drug- Eluting Stents. J Teh Univ Heart Ctr 2013;8(1):14-20. Keywords: Angioplasty • Drug-eluting stent • Treatment outcome • Graft occlusion, vascular • Prognosis *Corresponding Author: Mojtaba Salarifar, Assistant Professor of Interventional Cardiology, Cardiology Department, Tehran Heart Center, North Kargar Street, Tehran, Iran. 1411713138. Tel: +98 21 88029257. Fax: +98 21 88029256. E-mail: [email protected]. 14 J Teh Univ Heart Ctr 8(1) JANUARY 8, 2013 http://jthc.tums.ac.ir Mid-Term Follow-Up of Drug-Eluting Stenting for In-Stent Restenosis... TEHRAN HEART CENTER Introduction daily at least 3-5 days before the procedure or a 300-600 mg oral loading dose before catheterization at the discretion of I n-stent restenosis (ISR) remains one of the most the operator, followed by a daily oral administration of 75 difficult challenges in coronary interventional therapy since mg of the drug. The patients were encouraged to continue patients with ISR are at a higher risk for the recurrence of Clopidogrel therapy for a minimum of 6 months between restenosis.1, 2 The drug-eluting stent (DES), as compared 2003 and 2004 and a minimum of 12 months from 2005 to the bare-metal stent (BMS), has shown impressive onwards. Platelet GP IIb/IIIa inhibitors were administered at results for the prevention of restenosis in primary lesions. the operator’s discretion. Nevertheless, due to the increased use of the DES, the rate Upon the completion of the procedure, the patients were of ISR after DES implantation is becoming increasingly transferred to a monitored unit, where vascular access prevalent.3-7 Although in two recent controlled randomized sheaths, if still in place, were removed. trials, the DES was demonstrated to be superior to In-hospital mortality was defined as death within the same conventional brachytherapy in treating patients with intra- hospital admission regardless of the cause after PCI. For BMS ISR,8, 9 data regarding the role of the DES in treating all the patients, 12-lead electrocardiography was obtained intra-DES ISR are limited. prior and following intervention to detect procedure-related The use of the DES for the treatment of intra-BMS ISR and ischemic changes and/or the appearance of a new pathologic intra-DES ISR, both, has risen as a result of the simplicity Q wave on the surface electrocardiogram. After the procedure, of this approach and its effectiveness.10-12 Be that as it may, all the patients were checked for creatine kinase MB fraction little is known about the mid- and long-term outcomes with enzyme sampling at 8 and 16 hours (normal values up to 35 this procedure, particularly for DES-in-DES stenting. The IU/L). The diagnosis of non-Q wave myocardial infarction aim of this study was, therefore, to compare the one-year (MI) was considered as creatine kinase MB fraction clinical outcomes of DES stenting in patients with ISR after elevation greater than three times of the normal values in the the BMS versus DES implantation. absence of new pathologic Q-waves on electrocardiograms following intervention. Emergency coronary artery bypass grafting (CABG) was defined as CABG performed within 24 Methods hours after the index percutaneous procedure. Target lesion revascularization (TLR) was defined as clinically indicated Baseline clinical and angiographic data were obtained percutaneous or surgical revascularization of the index lesion from a computerized database of prospectively recorded during the follow-up, and target vessel revascularization clinical and procedural information on standardized forms (TVR) was defined as the revascularization of the vessel during the in-hospital period and at follow-up. After the formerly treated via PCI during the index hospitalization exclusion of primary PCI patients (410), a total of 11,249 through a repeat percutaneous intervention or bypass surgery. consecutive patients with 14,898 lesions underwent stenting The primary end-points of this study were late major at Tehran Heart Center between February 2004 and March adverse cardiac events (MACE), defined as death, non-fatal 2010. Of these patients, those with a first episode of ISR MI, and the need for TVR. Cumulative MACE was defined in whom a single DES was implanted were regarded as as in-hospital and one-year follow-up MACE. the study population. For ISR treatment, 131 (67.5%) first- The data on the early outcomes and occurrence of death, generation stents and 63 (32.5%) second-generation stents new non-fatal MI, need for CABG, and subsequent need for were implanted. Patients in whom the operators were unable repeat PCI in both groups were recorded. Follow-up was to place a stent and those who received a minimum of two scheduled at one month, 6 months, and 12 months and was stents were excluded from the study. conducted by clinic visits. If the patients were unable to return A comparison was made between 114 consecutive patients to the clinics, follow-up was performed using telephone (114 lesions) with the ISR of the initial BMS treated with the interviews, mailing, and reviewing hospital records. All the DES and 80 consecutive patients (with 80 lesions) with the patients had at least data on a one-year follow-up. ISR of the initial DES treated with the DES. Angiographic analysis was conducted based on the Informed consent was obtained from all the patients, consensus opinion of two experienced interventionists. and the study protocol was approved by the local Ethics ISR was defined as a luminal narrowing of more than 50% Committee. inside the stent or a segment at 5 mm within its vicinity. Using standard percutaneous techniques, percutaneous Angiographic ISR was classified according to the previously coronary intervention (PCI) and intracoronary stent reported Mehran classification.1 implantation were performed by operators, who relied on For the statistical analyses, statistical software SPSS their own judgment to assess stent expansion. All the patients version 15.0 for Windows (SPSS Inc., Chicago, IL) was used. were on Aspirin and received a heparin bolus of 7500-10000 All the p values were two-tailed, with statistical significance IU. The patients also received oral Clopidogrel (75 mg) once defined as a p value ≤ 0.05. The Journal of Tehran University Heart Center15 J Teh Univ Heart Ctr 8(1) JANUARY 8, 2013 http://jthc.tums.ac.ir The Journal of Tehran University Heart Center Negar Faramarzi et al. The continuous variables are expressed as mean ± standard The target vessel was predominantly the left anterior deviation (SD), and the categorical data are presented as descending artery (LAD), followed by the right coronary absolute frequencies and percentages. The continuous artery (RCA) and the left circumflex artery (LCX) in variables were compared using the Student t-test, and the both groups, but the distribution pattern was significantly categorical variables were compared using the chi-square (or different between the two groups (p value = 0.008) (Table the Fisher exact test, as required). 2). The ISR target lesion was a chronic total occlusion in 9% The authors of this manuscript hereby certify that they of the patients and a bifurcation lesion in 7% of the patients. have fully complied with the principles of the European Bifurcations and diffuse lesions were more prevalent in the Association of Science Editors (EASE) guidelines for intra-BMS ISR group than in the intra-DES ISR group (p authors and translators of scientific articles.13 value = 0.05 and p value = 0.02, respectively). Calcification, ostial location, and tortuous lesions were seen similarly in both groups. Lesion length was similar in both groups with Results a similar reference vessel diameter and baseline percent diameter stenosis. The study population’s baseline demographic and clinical Post-procedural coronary angiography demonstrated characteristics are shown in Table 1, and the angiographic similar residual stenosis in both groups with a non-significant and procedural characteristics are depicted in Table 2. No final lumen area higher in the intra-BMS ISR group (p value significant differences in the baseline demographic and = 0.24). Both groups presented predominantly with a type clinical characteristics were found between the “DES- II diffuse pattern of restenosis according to the Mehran sandwich” group and the DES-in-BMS group, except that classification1, and there was no statistically significant the patients with BMS ISR had a significantly higher level of difference between the groups with regard to the pattern of creatinine (p value = 0.03). In both groups, there was a high restenosis. prevalence of hyperlipidemia (75.4% and 70.0% in the intra- As is shown in Table 3, in-hospital events (death and BMS ISR and in the “DES-sandwich” group, respectively; p Q-wave MI) occurred with a similar frequency in both value = 0.90), denoting that hyperlipidemia was a common groups. Outcomes at twelve months were also similar risk factor in these groups of patients. Clinical presentation between the groups with respect to death, Q-wave MI, TVR, was found to be acute MI in 16% of the patients with a non- TLR, and overall MACE (Table 4). Although not significant, significant increase in the patients with DES ISR. Unstable there was a trend toward a higher TVR rate in the intra-DES angina and stable angina were the presenting syndromes in ISR group as compared to the intra-BMS group (0.9% BMS 38% and 37% of the patients, respectively; they were similar vs. 5.2% DES; p value = 0.16). The Kaplan-Meier curve of between the BMS and DES groups. MACE-free survival is illustrated in Figure 1. Cumulative Table 1. Baseline clinical characteristics* All patients (n=194) Intra-BMS ISR (n=114) Intra-DES ISR (n=80) P values** Age (y) 57.04±10.36 57.50±9.88 56.38±11.03 0.458 Male sex 130 (67.0) 77 (67.5) 53 (66.3) 0.850 LVEF (%) 51.60±8.86 51.71±8.69 51.44±9.15 0.892 Creatinine (mg/dl) 1.13±0.28 1.17±0.30 1.08±0.24 0.034 Diabetes mellitus 50 (25.8) 29 (25.4) 21 (26.3) 0.899 Hypertension 89 (45.9) 55 (48.2) 34 (42.5) 0.429 Hyperlipidemia 142 (73.2) 86 (75.4) 56 (70.0) 0.400 Current cigarette smoking 44 (22.7) 25 (21.9) 19 (23.8) 0.766 Family history of CAD 60 (30.9) 37 (32.5) 23 (28.8) 0.582 Previous myocardial infarction 73 (37.6) 39 (34.2) 34 (42.5) 0.241 Previous CABG 8 (4.1) 2 (1.8) 6 (7.5) 0.067 Previous stroke 3 (1.5) 1 (0.9) 2 (2.5) 0.570 Presenting symptom 0.606 Stable angina 89 (45.9) 56 (49.1) 33 (41.3) Unstable angina 74 (38.1) 42 (36.8) 32 (40.0) Non-STEMI 21 (10.8) 10 (8.8) 11 (13.8) STEMI 10 (5.2) 6 (5.3) 4 (5.0) *Data are presented as mean±SD or n (%) **P values for intra-BMS ISR versus intra-DES ISR LVEF, Left ventricular ejection fraction; CAD, Coronary artery disease; CABG, Coronary artery bypass grafting; STEMI, ST-segment elevation; MI, Myocardial infarction; BMS, Bare metal stent; DES, Drug-eluting stent; ISR, In-stent restenosis 16 J Teh Univ Heart Ctr 8(1) JANUARY 8, 2013 http://jthc.tums.ac.ir Mid-Term Follow-Up of Drug-Eluting Stenting for In-Stent Restenosis... TEHRAN HEART CENTER Table 2. Baseline lesion and procedural characteristics of the study population* Intra-BMS ISR (n=114) Intra-DES ISR (n=80) P value Target vessel 0.008 Left anterior descending 68 (59.6) 56 (70.0) Left circumflex 13 (11.4) 9 (11.3) Right coronary artery 33 (28.9) 11 (13.8) Saphenous vein graft 0 4 (5.0) Type B+C lesion 100 (87.7) 65 (81.3) 0.507 2 Lesion length (mm) 25.62±10.60 23.54±11.98 0.203 Reference vessel diameter (mm) 3.11±0.42 3.10±0.44 0.800 Chronic total occlusion 11 (9.6) 6 (7.5) 0.602 Bifurcations 11 (9.6) 2 (2.5) 0.050 Proximal lesion treated 49 (43.0) 41 (51.3) 0.256 Diffuse lesion 87 (76.3) 49 (61.3) 0.024 Long tubular lesion 14 (12.3) 17 (21.3) 0.093 Ostial lesion 8 (7.0) 5 (6.3) 0.833 Mehran Type ISR 0.103 I 31 (27.2) 21 (26.3) II 25 (48.2) 49 (61.3) III 20 (17.5) 5 (6.3) IV 8 (7.0) 5 (6.3) Stent length (mm) 28.48±6.47 27.31±7.70 0.522 Stent diameter (mm) 3.01±0.36 3.05±0.39 0.470 Stent overlapping 8 (7.0) 6 (7.5) 0.898 Residual stenosis 5 (4.4) 7 (8.8) 0.238 *Data are presented as mean±SD or n (%) BMS, Bare metal stent; DES, Drug-eluting stent; ISR, In-stent restenosis Table 3. In-hospital clinical outcomes of the study population* Intra-BMS ISR (n=114) Intra-DES ISR (n=80) P value Cardiac mortality 1 (0.9) 0 0.999 Myocardial infarction 4 (3.5) 3 (3.8) 0.999 Overall events 5 (4.4) 3 (3.8) 0.806 *Data are presented as n (%) BMS, Bare metal stent; DES, Drug-eluting stent; ISR, In-stent restenosis Table 4. Clinical events at one-year follow-up* Intra-BMS ISR (n=109) Intra-DES ISR (n=77) P value Cardiac mortality 0 0 - Target vessel revascularization 1 (0.9) 4 (5.2) 0.162 Target lesion revascularization 3 (2.8) 1 (1.3) 0.642 Non-fatal myocardial infarction 2 (1.8) 1 (1.3) 0.999 *Data are presented as n (%) BMS, Bare metal stent; DES, Drug-eluting stent; ISR, In-stent restenosis clinical MACE at one-year follow-up was 9.6% and 11.3% year follow-up, except for a trend toward more frequent in the DES-in-BMS and DES-in-DES groups, respectively TVR in the DES-in-DES group. Moreover, regardless of the (p value = 0.702). type of the initial stent (DES or BMS), the patients with ISR more commonly presented with acute coronary syndrome. This latter finding confirms the results of several previous Discussion studies reporting that intra-BMS ISR may not be as benign as once believed.14-16 The main finding of the present study is that the outcome Even in the DES era, restenosis remains the Achilles’ in the patients presenting with ISR was not different between heel of PCI. The use of the DES during PCI may have the two groups of DES-in-DES and DES-in-BMS at one- failed to eradicate the incidence of restenosis, but it has The Journal of Tehran University Heart Center17 J Teh Univ Heart Ctr 8(1) JANUARY 8, 2013 http://jthc.tums.ac.ir The Journal of Tehran University Heart Center Negar Faramarzi et al. Figure 1. Kaplan-Meier estimations of total major adverse cardiac events-free survival MACE, Major adverse cardiac events; BMS, Bare-metal stent; DES, Drug-eluting stent achieved a dramatic decrease in this complication, which study, however, hypothesized that the DES re-stenting would is the main drawback of the BMS implantation in patients demonstrate a similar outcome in both intra-DES ISR and with de novo lesions.17 Two landmark randomized trials,8, 9 intra-BMS ISR, and the preliminary results showed that the the SISR (Sirolimus in-stent restenosis) and the TAXUS-V post-procedural and follow-up minimal luminal diameter in-stent restenosis (ISR), compared the DES with vascular (MLD) rates were higher in the BMS group than in the DES brachytherapy in patients with post-BMS restenosis and groups. As a result, performance of the Sirolimus-eluting recommended the DES as the preferred modality for stent seems superior in the BMS restenosis than in the DES the treatment of patients with ISR. A meta-analysis of restenosis, with the limitation of differences in baseline randomized trials also demonstrated that the use of the characteristics including pre-procedural MLD.17 DES effectively reduced the risk of ISR recurrence after the A number of researchers have investigated the DES implantation of the BMS and was associated with superior implantation for patients with intra-DES ISR. Lemos et al.21 results as compared to plain balloon angioplasty and vascular examined 24 patients treated with DES-in-DES placement brachytherapy. Thus, the DES should be recommended as for intra-DES ISR and reported a recurrence rate of 18.2%, the treatment of choice for intra-BMS restenosis.18 suggesting relatively better results than those obtained with Although the use of the DES is associated with low rates other modalities. Cosgrave et al.12 compared outcomes in of TVR in patients with intra-BMS ISR and is considered to 174 patients with 201 lesions following similar DES versus be standard therapy in this group of patients,8, 9, 18, 19 outcomes different DES placement for intra-DES ISR and reported are less known in patients with intra-DES ISR treated with similar rates of TVR (15.9% vs. 16.0%) at follow-up. Garg repeat DES implantation (“DES sandwich” technique).19 To et al.22 reported a striking 28.8% rate of one-year TVR after date, only one randomized clinical trial, the ISAR-DESIRE the treatment of 116 patients with intra-DES ISR using (Intracoronary Stenting and Angiographic Results: Drug repeat DES implantation. Notably, 19.2% of the patients in Eluting Stents for In-Stent Restenosis)20 has been published. this study had been previously treated for ISR, representing This trial examined the treatment of intra-DES ISR with a a higher risk cohort than that in previous reports. Park et similar DES (homo-DES) versus a different DES (hetero- al.23 reported a high rate (53.6%) of recurrent restenosis DES) and showed no statistically significant differences following the treatment of intra-DES ISR with the DES, regarding the one-year clinical end-points of TLR (17% vs. while Solinas et al.24 observed the focal pattern of restenosis 15%), death/MI (6.1% vs. 5.8%), or stent thrombosis (0.4% in 69.5% of the intra-DES ISR lesions, and the TVR rate in in both groups). The final results of the CRISTAL study, a their series was 8% at one year. More recently, Steinberg et multi-center randomized clinical trial comparing the homo- al.19 reported outcome differences between intra-BMS ISR and hetero-DES with balloon re-angioplasty for the treatment and intra-DES ISR following the treatment of 238 patients of intra-DES restenosis and a comparator group with intra- using the DES. They observed significantly higher rates of BMS restenosis, have not yet been published in full. That TVR in the patients with intra-DES ISR than in those with 18 J Teh Univ Heart Ctr 8(1) JANUARY 8, 2013 http://jthc.tums.ac.ir Mid-Term Follow-Up of Drug-Eluting Stenting for In-Stent Restenosis... TEHRAN HEART CENTER intra-BMS ISR (22.2% vs. 10.3%; p value = 0.01), with a using meta-analysis techniques. Eur Heart J 2003;24:266-273. trend toward higher overall MACE (16% vs. 25.2%; p value 3. Dangas GD, Claessen BE, Caixeta A, Sanidas EA, Mintz GS, Mehran R. In-stent restenosis in the drug-eluting stent era. J Am = 0.08). In our study, although there was a non-significant Coll Cardiol 2010;56:1897-907. trend toward increases in TVR in the intra-DES ISR group, 4. Saia F, Lemos PA, Arampatzis CA, Hoye A, Degertekin M, TVR and angiographic recurrent restenosis were not only Tanabe K, Sianos G, Smits PC, van der Giessen WJ, de Feyter PJ, van Domburg RT, Serruys PW. Routine sirolimus eluting stent similar between intra-BMS ISR and intra-DES ISR but were implantation for unselected in-stent restenosis: insights from the also lower than the rates published in the literature. This Rapamycin Eluting Stent Evaluated at Rotterdam Cardiology difference could not be easily explained; it may, however, Hospital (RESEARCH) registry. Heart 2004;90:1183-1188. be because of the different baseline characteristics and 5. Dibra A, Kastrati A, Mehilli J, Pache J, Schuhlen H, von Beckerath N, Ulm K, Wessely R, Dirschinger J, Schomig A. Paclitaxel- immeasurable differences in patient treatment in our study eluting or sirolimus-eluting stents to prevent restenosis in diabetic as compared to the above-mentioned studies. patients. N Engl J Med 2005;353:663-670. Our study has several limitations. First, quantitative 6. Kastrati A, Mehilli J, von Beckerath N, Dibra A, Hausleiter J, Pache J, Schuhlen H, Schmitt C, Dirschinger J, Schomig A. Sirolimus- coronary angiographic or volumetric ultrasound was not eluting stent or paclitaxel-eluting stent vs balloon angioplasty conducted. Using angiography alone precluded an analysis for prevention of recurrences in patients with coronary in-stent of the differences in the patterns of restenosis or neointimal restenosis: a randomized controlled trial. JAMA 2005;293:165- plaque morphologic characteristics, which may have 171. 7. Stone GW, Ellis SG, Cannon L, Mann JT, Greenberg JD, Spriggs D, confounded the present findings. Second, this study was O’Shaughnessy CD, DeMaio S, Hall P, Popma JJ, Koglin J, Russell retrospective in its nature and may be subject to selection ME. Comparison of a polymer-based paclitaxel-eluting stent with a bias. Finally, the study involved a small group in total and bare metal stent in patients with complex coronary artery disease: a randomized controlled trial. JAMA 2005;294:1215-1223. particularly the number of the patients in the intra-DES ISR 8. Holmes DR, Jr, Teirstein P, Satler L, Sketch M, O’Malley J, Popma group was too small to compare the outcome within the JJ, Kuntz RE, Fitzgerald PJ, Wang H, Caramanica E, Cohen SA. different types of the DES. Sirolimus-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the SISR randomized trial. JAMA 2006;295:1264-1273. 9. Stone GW, Ellis SG, O’Shaughnessy CD, Martin SL, Satler L, Conclusion McGarry T, Turco MA, Kereiakes DJ, Kelley L, Popma JJ, Russell ME. Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the TAXUS V ISR randomized Our results suggest that, regardless of the type of the initial trial. JAMA 2006;295:1253-1263. stent (DES or BMS), the patients with ISR more commonly 10. Torguson R, Sabate M, Deible R, Smith K, Chu WW, Kent KM, presented with acute coronary syndrome. This finding Pichard AD, Suddath WO, Satler LF, Waksman R. Intravascular confirms the results of several previous studies reporting that brachytherapy versus drug-eluting stents for the treatment of patients with drug-eluting stent restenosis. Am J Cardiol intra-BMS ISR may not be as benign as once believed. We 2006;98:1340-1344. also found that the outcome of the patients presenting with 11. Kim YH, Lee BK, Park DW, Park KH, Choi BR, Lee CW, Hong ISR was not different between the two groups of DES-in- MK, Kim JJ, Park SW, Park SJ. Comparison with conventional DES and DES-in-BMS at one-year follow-up, except that therapies of repeated sirolimus-eluting stent implantation for the treatment of drug-eluting coronary stent restenosis. Am J Cardiol there was a trend toward more frequent TVR in the DES-in- 2006;98:1451-1454. DES group. DES-in- DES implantation for restenosis seems 12. Cosgrave J, Melzi G, Corbett S, Biondi-Zoccai GG, Babic R, feasible and safe with a relatively low incidence of MACE at Airoldi F, Chieffo A, Sangiorgi GM, Montorfano M, Michev I, Carlino M, Colombo A. Repeated drug-eluting stent implantation one-year follow-up. for drug-eluting stent restenosis: the same or a different stent. Am Heart J 2007;153:354-359. 13. Ufnalska SB. Free help for Scientists and Translators. J Teh Univ Acknowledgment Heart Ctr 2011;6:206-210. 14. Chen MS, John JM, Chew DP, Lee DS, Ellis SG, Bhatt DL. Bare metal stent restenosis is not a benign clinical entity. Am Heart J This study was supported by Tehran Heart Center, Tehran 2006;151:1260-1264. University of Medical Sciences. We gratefully thank Dr. 15. Doyle B, Rihal CS, O’Sullivan CJ, Lennon RJ, Wiste HJ, Bell M, Bresnahan J, Holmes DR, Jr. Outcomes of stent thrombosis and Arash Jalali for statistical analyses. restenosis during extended follow-up of patients treated with bare- metal coronary stents. 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