Interventional Cardiology

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1 Clinical Investigations Interventional Cardiology Does stent design affect probability of restenosis? A randomized trial comparing Multilink stents with GFX stents Yuji Yoshitomi, MD, PhD, a Shunichi Kojima, MD, PhD, b Michiko Yano, MD, a Toshihiko Sugi, MD, a Yuji Matsumoto, MD, a Masao Saotome, MD, a Kyoe Tanaka, MD, a Michiko Endo, MD, a and Morio Kuramochi, MD, PhD a Shizuoka, Japan Background Experimental studies have revealed that stent configuration influences intimal hyperplasia. The purpose of this study was to evaluate clinical outcomes for 2 stent designs in a randomized trial with quantitative coronary angiography (QCA) and intravascular ultrasonography (IVUS). Methods We randomly assigned 100 patients with 107 lesions and symptomatic coronary artery disease to deployment of a Multilink stent (Advanced Cardiovascular Systems, Guidant, Santa Clara, Calif) or a GFX stent (Applied Vascular Engineering, Santa Rosa, Calif) with IVUS guidance. QCA and IVUS studies were performed before and after intervention and at follow-up (4.2 ± 1.0 months). Results There were no significant differences in baseline characteristics and QCA and IVUS parameters before and after intervention between the 2 groups. However, minimal lumen diameter at follow-up was significantly larger in the Multilink group (2.46 ± 0.59 vs 2.08 ± 0.79 mm, P <.05). Maximal in-stent intimal hyperplasia was significantly larger in the GFX group (2.9 ± 1.7 vs 1.8 ± 1.2 mm 2, P <.01). The restenosis rate differed between the 2 groups (Multilink 4% vs GFX 26%, P =.003). In multiple stepwise logistic regression analysis, the only predictor that significantly correlated with restenosis was stent type (P <.01). The odds ratio for the GFX stent treated vessels was (95% confidence interval ). Conclusions With deployment of the GFX stent, a thicker neointima develops within the stent. Stent configuration may affect clinical outcomes. (Am Heart J 2001;142: ) See related Editorial on page 378. In an animal model it has been suggested that stent surface material and geometric configuration may be more important than operator-dependent variables in determining the degree of neointimal hyperplasia and thrombosis. 1 In addition, design characteristics such as hoop strength and metallic surface area have been shown to influence neointimal formation. 2,3 Several randomized trials to compare one stent with a reference stent (Palmaz-Schatz stent) have been carried out. 4-6 Although a number of new stents have been developed and are cur- From the a Division of Cardiology, and the b Department of Clinical Research, Tohsei National Hospital, Shizuoka, Japan. Submitted February 29, 2000; accepted October 26, Reprint requests: Yuji Yoshitomi, MD, PhD, Division of Cardiology, Tohsei National Hospital, 762-1, Nagasawa, Shimizu-cho, Suntoh-gun, Shizuoka 411, Japan. ytommy@sage.ocn.ne.jp Copyright 2001 by Mosby, Inc /2001/$ /1/ doi: /mhj rently under evaluation, the exact relationship between stent design and clinical outcome is unclear. Several studies suggested that intravascular ultrasonography (IVUS) helps to identify patients with suboptimal stent results. 7-9 Also, according to specific IVUS criteria, this tomographic imaging modality has an impact on restenosis. 9,10 Furthermore, IVUS permits direct visualization of intensely echoreflective stainless-steel stent struts and, as a result, measurement of neointimal thickness. The ACS Multilink stent (Advanced Cardiovascular Systems, Guidant, Santa Clara, Calif) is a new device that is more flexible than the Palmaz-Schatz stent, and it has a high degree of axial and radial strength. 11,12 On the other hand, the AVE GFX stent (Applied Vascular Engineering, Santa, Rosa, Calif), the fourth generation of AVE Micro stent, has the radial strength of a tubular stent and the flexibility of a coil. 13 We conducted a randomized study to compare the early and late clinical and angiographic outcomes of Multilink and GFX stent implantation with IVUS guidance.

2 446 Yoshitomi et al American Heart Journal September 2001 Methods This was a single center, randomized, single-blinded study. The protocol was approved by our institutional review board on clinical study. Study patients The study population consisted of patients with symptomatic ischemic heart disease and acute myocardial infarction within 6 hours of the onset of chest pain. They had single-vessel or native multivessel disease with >75% stenosis of the culprit lesion and underwent stent implantation as a primary choice or the stenting after percutaneous transluminal coronary angioplasty with extensive dissection or a suboptimal result. The exclusion criteria were (1) lesion length >20 mm, (2) a reference vessel diameter <2.75 mm, (3) acute myocardial infarction with cardiogenic shock, (4) the presence of multiple focal lesions or diffuse disease, (5) serious disease in the left main coronary artery, (6) saphenous vein graft stenosis, (7) previous bypass surgery, and (8) ostial lesions. All patients gave their written, informed consent to participate in the study, after possible risks and benefits of the protocol were explained. Stent implantation procedure Baseline angiography and IVUS were performed after the administration of 0.5 mg of intracoronary nitroglycerin. Patients were randomized to GFX or Multilink stent implantation. Randomization into 2 groups was done by means of sealed envelopes after conventional angioplasty. After removal of the delivery system and administration of 0.5 mg of intracoronary nitroglycerin, angiography and IVUS imaging was performed. Because the Multilink stent used in this series of patients was only 15 mm long, for longer lesions which could not be covered by a single stent 2 stents were permitted. The angiographic criteria for successful stenting were (1) a quantitative estimate of residual coronary stenosis <20% of the lumen diameter within the stent, (2) the stent was effectively positioned at the intended site, and (3) anterograde flow of Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 perfusion. An optimal stent expansion was defined as minimal stent area 90% of the average reference lumen areas or 100% of lumen area of the reference segment with the lowest lumen area. 14 Medical therapy and follow-up Heparin therapy was stopped within 24 hours after angioplasty. Patients were administered aspirin (243 mg/d) and ticlopidine (200 mg/d) or cilostazol (200 mg/day) after stenting for 3 months. 15 We measured serial creatine phosphokinase levels in patients with acute coronary syndrome. Creatine kinase levels were also measured at the next day of intervention in other patients. We did not use abciximab. Patients were asked to return for clinical evaluation at 3 and 6 months after the procedure. Follow-up angiography was performed at 4 months, or earlier if clinically indicated. Clinical evidence of procedural success was defined as angiographic evidence of success without a major complication (death, myocardial infarction, or coronary artery bypass graft surgery) during the hospitalization. Quantitative coronary angiographic analysis All cineangiograms were analyzed with a computer-assisted automated edge detection algorithm by 2 observers who did not know the protocol and outcomes. At least 2 orthogonal projections were selected for analysis. Quantitative coronary angiography (QCA) was carried out with use of the 8F guiding catheter for calibration. Reproducibility of QCA was described previously. 15,16 Acute gain and late loss were adapted to represent the improvement in minimal lumen diameter (MLD) achieved at intervention (MLD after stenting minus MLD before ballooning) and the change at follow-up (MLD after stenting minus MLD at follow-up), respectively. Angiographic restenosis was defined as a follow-up percent diameter stenosis 50%. IVUS imaging protocol IVUS imaging was performed with a system (Cardiovascular Imaging Systems, San Jose, Calif) that used a 30-MHz, singleelement, beveled transducer mounted on the end of a flexible shaft and rotated at 1800 revolutions/min within either a 2.9F long monorail/common distal lumen imaging sheath or a 3.2F short monorail imaging sheath. The transducer was withdrawn within the stationary imaging sheath at a speed of 0.5 mm per second with a motorized transducer pullback device. Studies were recorded on a high-resolution s-vhs videotape for offline analysis. A complete ultrasonographic imaging run was performed from beyond the culprit lesion to the aorto-ostial junction after administration of 0.5 mg of intracoronary nitroglycerin. Quantitative IVUS analysis IVUS images were analyzed offline with the Cardiovascular Imaging System (San Jose, Calif). With use of computerized planimetry, we measured the vessel area and lumen area at the lesion site and at the reference segments. 17 The plaque + media area was calculated as vessel area minus lumen area. Percent plaque burden was calculated as plaque + media area/vessel area 100. The lumen area at the stent level was assessed by planimetry at multiple levels (at least 3), and the smallest area was chosen. The same anatomic image slice was analyzed before and after intervention. Symmetry index was calculated by minimal stent diameter divided by maximal stent diameter. Maximal in-stent tissue growth was in-stent intimal hyperplasia at the maximal site at follow-up. The differences in repeated measurements of the vessel area, stent area, and lumen area were 4.0% ± 2.3%, 3.7% ± 2.0%, and 3.3% ± 3.0%, with correlation coefficient values of 0.93, 0.96, and 0.92, respectively. Statistical analysis The West study with Multilink stent reported that the restenosis rate was 12%, whereas the restenosis rate of Microstent (Applied Vascular Engineering, Santa Rosa, Calif) was 30%. 18,19 Therefore we assumed that the difference of the restenosis rate was 18% between the 2 groups. The sample size was calculated accordingly; 2 groups of 59 patients were needed (α 5%, β 20%, 2-sided situation). Data were expressed as mean ± SD and percentage. Comparison of continuous variables between the groups was performed with the paired or unpaired Student t test (two tailed). Comparisons of categorical variables were made by χ 2 tests. Subgroup QCA data in GFX group was compared by analysis of variance for repeated measures. Univariate logistic

3 American Heart Journal Volume 142, Number 3 Yoshitomi et al 447 Table I. Baseline clinical characteristics Multilink GFX stent stent (n = 51) (n = 49) Age (y) 63 ± 9 63 ± 10 Sex (M/F) 38/13 38/11 Diagnosis Angina pectoris 15 (29%) 13 (27%) Unstable angina pectoris 3 (6%) 4 (8%) Previous myocardial infarction 20 (39%) 19 (39%) Acute myocardial infarction 13 (25%) 13 (27%) Risk factor Hypertension 26 (51%) 29 (59%) Diabetes mellitus 18 (35%) 16 (33%) Hypercholesterolemia 22 (43%) 18 (37%) Smoking 34 (67%) 38 (78%) Coronary arteriography Single-vessel disease 23 (45%) 27 (55%) Multivessel disease 28 (55%) 22 (45%) Previous angioplasty 5 (10%) 6 (12%) Previous coronary artery bypass grafting 0 0 Antiplatelet therapy Ticlopidine 6 (12%) 7 (14%) Cilostazol 45 (88%) 42 (86%) Follow-up angiography (mo) 4.3 ± ± 1.5 Values are expressed as mean ± SD or number (%) of patients. Table II. Baseline angiographic and procedural characteristics Multilink GFX stent stent (55 lesions) (52 lesions) Stented artery Left anterior descending artery 28 (51%) 25 (48%) Right circumflex artery 18 (33%) 15 (29%) Left circumflex artery 9 (16%) 12 (23%) Lesion type* A 9 (16%) 7 (13%) B1 17 (31%) 16 (31%) B2 25 (45%) 28 (54%) C4 (7%) 1 (2%) Specific indication for stenting Elective 46 (84%) 35 (67%) Suboptimal results 1 (2%) 4 (8%) Threatened closure 0 2 (4%) Primary stenting 8 (15%) 11 (21%) Multiple stenting 9 (16%) 0 Stent length (mm) 12 NA 9 (17%) (100) NA 18 NA 31 (60%) 24 NA 12 (23%) Data are expressed as number (%). NA, Not available. *American College of Cardiology/American Heart Association criteria. regression analysis was used to select the independent predictive factors for angiographic restenosis within the entire study population. Covariates examined included clinical characteristics (age, sex, diagnosis, and risk factors), stent type, stent balloon size, stent length, number of stents, final balloon size, lesion morphologic features (target vessel, American College of Cardiology/American Heart Association type), and QCA factors (lesion length, reference diameter, preprocedural and postprocedural MLD, and percent diameter stenosis (DS) before and after the procedure). Univariate predictors of angiographic restenosis with a P value <.05 were entered into a multivariate logistic regression model with stepwise selection. Differences were considered statistically significant at a value of P <.05. Results Baseline characteristics From January 1997 through December 1998, 100 patients with 107 lesions were enrolled in this study. The baseline clinical and angiographic characteristics are shown in Table I. There were no significant differences in age, sex, diagnosis, and risk factors. Baseline angiographic and procedural characteristics There were no significant differences in lesion location and lesion type (Table II). Two Multilink stents were implanted into 9 lesions because of long lesions or coronary dissections. Six lesions were implanted with 24-mm GFX stents because of coronary dissections. There were no significant differences in reference diameter and preprocedural MLD between the 2 groups (Table III). No patient crossed over to another Table III. Quantitative coronary angiographic results Multilink GFX stent stent (n = 55) (n = 52) Reference diameter (mm) Pre 3.15 ± ± 0.59 Post 3.18 ± ± 0.51 Follow-up 3.08 ± ± 0.54 MLD (mm) Pre 0.50 ± ± 0.39 Post 2.95 ± ± 0.52 Follow-up 2.46 ± 0.59* 2.08 ± 0.79 % Diameter stenosis Pre 81 ± ± 12 Post 7 ± 10 8 ± 12 Follow-up 21 ± 13* 33 ± 23 Lesion length (mm) 10.1 ± ± 5.7 Stent balloon size (mm) 3.4 ± ± 0.3 Post inflamation 52 (95%) 43 (83%) Final balloon size (mm) 3.5 ± ± 0.3 Maximal inflation pressure (mm) 16.2 ± ± 2.6 Difference in MLD (mm) Acute gain 2.35 ± ± 0.55 Late loss 0.52 ± ± 0.72 Angiographic success (%) Clinical success (%) Restenosis 2/50 (4%) 12/47 (26%) Target lesion revascularization rate at 6 mo 2/53 (4%) 6/48 (13%) Data are expressed as mean ± SD or number (%). Pre, Before intervention; Post, after stent implantation. *P <.05 versus GFX stent. P <.01 versus GFX stent. P =.003 versus GFX stent.

4 448 Yoshitomi et al American Heart Journal September 2001 Table IV. Subgroup analysis of quantitative coronary angiographic results in GFX group 12 mm (n = 9) 18 mm (n = 31) 24 mm (n = 12) Reference diameter (mm) Pre 2.98 ± ± ± 0.43 MLD (mm) Pre 0.70 ± ± ± 0.34 Post 2.99 ± ± ± 0.52 Follow-up 1.69 ± ± ± 0.82 % DS Pre 77 ± 6 87 ± ± 11 Post 8 ± 9 8 ± 13 8 ± 14 Follow-up 42 ± ± ± 23 Lesion length (mm) 6.2 ± ± ± 4.9 Stent balloon size (mm) 3.3 ± ± ± 0.2 Difference in MLD (mm) Acute gain 2.29 ± ± ± 0.55 Late loss 1.38 ± ± ± 0.65 Restenosis 2/8 (25%) 6/27 (22%) 4/12 (33%) Target lesion revascularization rate at 6 mo 1/8 (13%) 3/28 (11%) 2/12 (17%) Data are expressed as mean ± SD or number (%). Pre, Before intervention; Post, after stent implantation. stent group. Procedural success and clinical success were similar in the 2 groups. Follow-up One patient in the Multilink group and 2 patients in the GFX group who had acute myocardial infarction died from ventricular arrhythmia after successful primary stenting during hospitalization. The ventricular arrhythmias were confirmed by cardiac care unit monitoring. One patient in the Multilink group and 1 patient in the GFX group showed subacute occlusion. No patients had Q-wave myocardial infarction or coronary artery bypass graft surgery. One patient in the Multilink group and 1 patient in the GFX group had femoral hematomas but neither required surgical repair or transfusion. Clinical follow-up could be completed for all study patients, whereas a repeat angiography was performed at 4.2 ± 1.0 months in 91 patients with 97 lesions (91% of the study population), 50 lesions of the Multilink group (91%) and 47 lesions of the GFX group (90%). Angiography was not repeated in 9 patients, 3 patients died during hospitalization, 2 patients showed subacute occlusion, and 4 patients refused the procedure. A total of 8 patients underwent repeat angioplasty during 6 months after stent implantation. All 8 patients who underwent target lesion revascularization had recurrent angina. No case of myocardial infarction was observed during the follow-up period. Quantitative coronary angiographic results The QCA parameters before and after intervention were similar between the 2 groups (Table III). However, MLD at follow-up was greater in the Multilink group than in the GFX group (P <.01). Acute gain was similar, but late loss was larger in the GFX group than in the Multilink group. There was a significant difference in the angiographic restenosis rate: 4% in the Multilink group and 26% in the GFX group (P =.003). In the GFX group, 73% of restenosis lesions had a stent length of 12 or 18 mm. There were no significant differences in QCA parameters before and after intervention between restenotic lesions and no restenotic lesions. Table IV shows subgroup analysis in the GFX group. There were no significant differences in QCA parameters. The restenosis rate did not differ among the 3 subgroups. Table V shows the results of another subgroup analysis. There were similar results in patients with acute coronary syndrome (group A) or stable angina pectoris and old myocardial infarction (group S). The MLD at follow-up of the Multilink group was greater than that of the GFX group in both groups A and S (P <.05). A significant difference appeared between the Multilink group and the GFX group in the restenosis rate in group S (P <.05) but without a significant difference in group A. Among patients who underwent primary stenting, there were no significant differences in QCA parameters before and after intervention and at follow-up between the GFX and Multilink groups. All these lesions revealed no restenosis at follow-up. IVUS results Because IVUS studies were not performed in 16 lesions as a result of tortuosity of the culprit lesion, IVUS data were available for 91 lesions both before and after intervention. Online analysis showed that 1 of the

5 American Heart Journal Volume 142, Number 3 Yoshitomi et al 449 Table V. Quantitative coronary angiographic results in subgroups Multilink stent GFX stent Group A Group S Group A Group S (n = 16) (n = 39) (n = 17) (n = 35) Reference diameter (mm) 3.27 ± ± ± ± 0.56 MLD (mm) Pre 0.30 ± ± ± ± 0.36 Post 2.95 ± ± ± ± 0.58 Follow-up 2.50 ± 0.54* 2.45 ± 0.60* 2.05 ± ± 0.81 % DS Pre 90 ± ± ± ± 10 Post 8 ± 11 6 ± ± 13 7 ± 12 Follow-up 24 ± 11* 20 ± ± ± 23 Lesion length (mm) 9.8 ± ± ± ± 4.4 Difference in MLD (mm) Acute gain 2.59 ± ± ± ± 0.53 Late loss 0.49 ± ± ± ± 0.72 Restenosis 0/11 (0%) 2/39 (5%)* 4/14 (29%) 8/33 (24%) Target lesion revascularization rate at 6 mo 0/14 (0%) 2/39 (5%) 1/14 (7%) 5/34 (15%) Data are expressed as mean ± SD or number (%). Group A, Acute coronary syndrome; Group S, stable angina pectoris or previous myocardial infarction; Pre, before intervention; Post, after stent implantation. *P <.05 versus GFX stent. P <.01 versus GFX stent. 2 criteria for optimal stent expansion was not reached in 15 of 92 lesions (16%) from final IVUS assessment (8 lesions in the Multilink group and 7 lesions in the GFX group). IVUS images were available for 75 of 97 lesions with angiographic follow-up. Table VI shows IVUS results. Vessel area, lumen area and plaque burden at proximal and distal reference segments were similar in the 2 groups. There were no significant differences in vessel area, lumen area, and plaque + media area at the lesion site before and after intervention between the 2 groups. However, maximal in-stent tissue growth was lower in the Multilink group than in the GFX group (P <.01). There were no significant differences in IVUS parameters before and after intervention between restenotic lesions and no restenotic lesions. Predictors of restenosis By univariate logistic regression analysis, stent type, stent length, and hypercholesterolemia were significant variables. In multiple stepwise logistic regression analysis the only predictor that significantly correlated with restenosis was stent type (P <.01). The odds ratio for the GFX stent treated vessels was (95% confidence interval ). Discussion This study shows that a Multilink stent is more favorable with regard to neointimal hyperplasia and restenosis rate compared with a GFX stent. Stent design may influence the clinical outcomes. Table VI. Intravascular ultrasonographic measurements Multilink stent GFX stent Proximal reference segment n = 46 n = 45 Vessel area (mm 2 ) 15.6 ± ± 3.6 Lumen area (mm 2 ) 8.6 ± ± 3.2 Plaque burden (%) 45 ± ± 14 Distal reference segment n = 46 n = 45 Vessel area (mm 2 ) 12.1 ± ± 4.6 Lumen area (mm 2 ) 6.9 ± ± 2.8 Plaque burden (%) 43 ± ± 14 Lesion site Before intervention n = 46 n = 45 Vessel area (mm 2 ) 14.2 ± ± 3.8 Lumen area (mm 2 ) 2.1 ± ± 0.6 Plaque + media area (mm 2 ) 12.1 ± ± 3.6 Plaque burden (%) 84 ± 6 85 ± 5 After intervention n = 47 n = 45 Minimal lumen area (mm 2 ) 8.4 ± ± 2.2 Symmetric index 0.87 ± 0.08* 0.90 ± 0.08 At follow-up n = 40 n = 35 Minimal lumen area (mm 2 ) 6.8 ± 2.6* 5.5 ± 2.4 Maximal in-stent tissue 1.8 ± ± 1.7 growth (mm 2 ) Data expressed are mean value ± SD. Maximal in-stent tissue growth, In-stent intimal hyperplasia at the maximal site at follow-up. *P <.05 versus GFX stent. P <.01 versus GFX stent. Previous studies By comparison of the slotted tube design with the tubular corrugated ring flexible design, such as the Multilink stent, in an animal model, it was shown that the

6 450 Yoshitomi et al American Heart Journal September 2001 latter leads to lower injury to the wall, lower platelet accumulation, and less restenosis at 3 months. 1 In addition, it has been shown that the lower-hoop-strength, high-profile tantalum Strecker stent evokes a greater degree of neointimal formation than the lower-profile, higher-hoop-strength Palmaz-Schatz stent and Wall stent in the dog. 20 To resolve the issue of whether stent configuration plays a major role in determining long-term outcome, large randomized trials are under way comparing various stent designs. 4-6 The ACS Multilink Stent Clinical Equivalence in de Novo Lesions Trial (ASCENT) randomized to either Palmaz-Schatz or Multilink stent implantation demonstrated that the angiographic restenosis rates tend to be lower for the Multilink stent (21% vs 16%). 5 Equivalence between the Palmaz-Schatz stent and the Micro Stent II was shown in the Study of Micro-Stent s Ability to Limit Restonosis Trial (SMART) (23% vs 25%). 4 The Gianturco-Roubin II stent had a more binary restenosis rate than the Palmaz-Schatz stent. 6 The reasons for these differences may be due in part to a higher acute residual stenosis after stent implantation in the Gianturco-Roubin II stent treated vessels. However, it is questionable what practical purpose will be served for comparing all the available stents with the standard (Palmaz-Schatz stent), which has excessive rigidity, an articulation, and incomplete expansion. Stent design There are at least 5 parameters that differ from stent to stent design, including longitudinal flexibility versus rigidity, hoop strength, gauge of wire, type of material, and differences in surface area. The Multilink stent is carved from a stainless steel cylinder and is composed of 12 corrugated rings interconnected by 33 articulations, with a strut thickness of inch and a metallic surface area of <15% after expansion. 21 The GFX stent consists of connected stainless steel segments, with strut thickness of inch and a metallic surface area of >20% after expansion. 21 In this study MLD, percent DS, and maximal in-stent tissue growth at follow-up differed between the 2 groups. The wire thickness of the GFX stent is nearly 2-fold greater than that of the Multilink stent. Increased neointimal formation with larger stent wire thickness has been reported. 1,22 Moreover, in one study where a coil stent with different gap sizes was implanted in animal models, it was shown that the proliferative response is enhanced when no gaps are left between coils. 3 The differences in metallic surface area, strut thickness, and configuration may be related to extent of intimal hyperplasia. IVUS-guided stent implantation IVUS imaging has been used extensively over the last few years in an effort to improve our understanding of stent deployment characteristics and to define IVUS guidelines for implantation. Previous studies showed that the restenosis rate after use of the Multilink stent was 17% to 20%. 18,23 However, IVUS-guided stent implantation was not performed in these previous studies. IVUS-guided stent deployment produced a significantly greater MLD than did angiography-guided stenting. MLD and stent area after intervention in this study were larger than previous studies. 11,18 Hoffmann et al 24 reported that predictors of angiographic restenosis were postinterventional MLD and lumen area. Larger postprocedural MLD and lumen area may be related to the differences in the Multilink-treated vessels. On the other hand, the GFX group showed a higher restenosis rate than the Multilink group did, although the lumen area after stent implantation was similar in the 2 groups. A recent study suggests that the restenosis rate after the GFX stent without IVUS guidance is 30%. 25 An experimental study suggested that geometric configuration of stents may be more important than postinterventional MLD in determining neointimal hyperplasia. 1 There are very few IVUS-guided studies to examine whether stent configuration influences in-stent restenosis in humans. Our study supports that stent configuration is more closely related to intimal hyperplasia rather than postinterventional lumen area. Study limitations The relatively small number of patients eligible for analysis in this study may render it difficult to generalize the results and to apply them to other patient populations with possibly different lesion characteristics (eg, smaller culprit vessels and diffuse lesions). Restenosis trials with <90% angiographic follow-up suffered from selection bias. 26 However, our follow-up rate was 91%. The majority of the patients returned for angiographic and IVUS studies. Although this study was a prospective, randomized study, the major limitation of the study was that we cannot achieve a sample size because of ethical reasons. If restenosis similarly occurred in the 2 groups, the estimated restenosis rate was 4 of 59 (7%) in the Multilink group and 14 of 59 (24%) in the GFX group. This showed a statistical significance (P =.01). Because of these results, this trial was discontinued. In addition, our follow-up angiography at 4 months may be too short to fully evaluate the restenosis after stenting. However, there was no significant difference in followup periods between the 2 groups. We used 2 Multilink stents in 16% of lesions and 24- mm GFX stents in 23% of lesions. Several reports suggested that predictors of in-stent restenosis after Palmaz-Schatz stent implantation were diabetes, stent length, multiple stents, and smaller final MLD. 27,28 However, these studies evaluated the first-generation

7 American Heart Journal Volume 142, Number 3 Yoshitomi et al 451 stents, such as the Palmaz-Schatz stent. Stent type is an additional factor associated with in-stent restenosis. Conclusions The Multilink stent had favorable clinical outcomes compared with the GFX stent. The mechanisms underlying these differences are probably related to the design of the configuration and the thickness of the wire between the 2 stents. We thank the nurses and physicians who helped us in this study and Ms Hiromi Hosaka for secretarial assistance. References 1. Rogers C, Edelman ER. Endovascular stent design dictates experimental restenosis and thrombosis. Circulation 1995;91: Fontaine AB, Spigos DG, Eaton G, et al. Stent induced intimal hyperplasia: are there fundamental differences between flexible and rigid stent design? J Vasc Interv Radiol 1994;5: Tominaga R, Kambic HE, Emoto H, et al. Effects of design geometry of intravascular endoprostheses on stenosis rate in normal rabbits. 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