Relation of stent design and stent surface material to subsequent in-stent intimal hyperplasia in coronary arteries determined by intravascular ultrasound

Relation of Stent Design and Stent Surface Material to Subsequent In-Stent Intimal Hyperplasia in Coronary Arteries Determined by Intravascular Ultrasound Rainer Hoffmann, MD, Gary S. Mintz, MD, Philipp K. Haager, MD, Togul Bozoglu, Eberhard Grube, MD, Michael Gross, MD, Christian Beythien, MD, Harald Mudra, MD, Ju¨rgen vom Dahl, MD, and Peter Hanrath, MD A variety of different stent designs and coatings have become available. This study sought to determine the impact of stent design and gold-coating of stents on intimal hyperplasia (IH) in human atherosclerotic coronary arteries in relation to known predictors of restenosis. Angiographic and intravascular ultrasound (IVUS) studies were performed at 6-month follow-up on 311 native coronary lesions of 311 patients treated with 99 Multi-Link stents, 74 InFlow steel stents, 73 InFlow goldcoated stents, 41 Palmaz-Schatz stents, 12 NIR steel stents, and 12 gold-coated NIR Royal stents. Lumen and stent cross-sectional area (CSA) were measured at 1-mm axial increments. Mean IH CSA (stent CSA ⴚ lumen CSA) and mean IH thickness were calculated and averaged over the total stent length. IVUS demonstrated different

levels of IH for the 6 stents. Mean IH thickness ranged from 0.20 ⴞ 0.13 mm for Multi-Link stents to 0.43 ⴞ 0.14 mm for InFlow goal-coated stents (p <0.001). Multivariate analysis proved non–Multi-Link stent design (odds ratio 3.45, 95% confidence intervals 1.13 to 11.11, p <0.034) and gold coating (odds ratio 3.78, 95% confidence intervals 1.88 to 7.54, p <0.001) to be the only independent predictors of IH thickness >0.3 mm. In conclusion, stent design and surface material have an important impact on the IH response to stents implanted in human coronary arteries. However, the differences in IH thickness between the analyzed stents were relatively small compared with the absolute lumen dimensions. 䊚2002 by Excerpta Medica, Inc. (Am J Cardiol 2002;89:1360 –1364)

eduction of restenosis is the main advantage of stenting compared with conventional percutaneR ous transluminal coronary angioplasty. Intimal hy-

amount of IH reaction than the binary restenosis rate obtained by angiographic analysis.11 In this IVUS follow-up study that included 6 different stent types (4 different designs and gold coated as well uncoated steel stents), the importance of stent design and stent surface material for IH was analyzed in comparison with known patient, lesion, and procedure-related predictors of restenosis.

1,2

perplasia (IH) is the mechanism of stent restenosis.3 Several patient and lesion-related predictors of stent restenosis have been defined from angiographic studies.4 – 6 These analyses predominantly included the Palmaz-Schatz stent. Thus, stent design and stent surface material have not been considered as possible predictors of restenosis. Stent design has been shown in histologic restenosis studies to have an important impact on the amount of IH.7–9 In addition, an angiographic study has shown that gold coating of stents increases restenosis rates compared with a steel stent surface.10 Angiographic parameters of restenosis are related to the luminal dimensions at the smallest point within the stent or lesion length. Intravascular ultrasound (IVUS) studies allow improved assessment of tissue proliferation throughout the stented vessel length, thus permitting a more precise analysis of the From the Medical Clinic I, University RWTH Aachen, Aachen, Germany; Cardiovascular Research Foundation, New York, New York; Department of Cardiology, Heart Center Siegburg, Siegburg; Department of Cardiology, University Clinic Charite, Berlin; Department of Cardiology, University Hamburg, Hamburg; and Department of Cardiology, Krankenhaus Neuperlach, Munich, Germany. Manuscript received January 18, 2002; revised manuscript received and accepted February 21, 2002. Address for reprints: Rainer Hoffmann, MD, Medical Clinic I, University RWTH Aachen, Pauwelsstraße 30, 52057 Aachen, Germany. E-mail: [email protected].

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©2002 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 89 June 15, 2002

METHODS

Patients and lesions: Consecutive patients from 4 studies who required IVUS follow-up at 6 months were included in this study. A differenct stent design was used in each study. Lesion inclusion criteria were similar for the 4 studies. Coronary lesions had to be located in a native artery of 2.5 to 4.0 mm diameter and lesion length (up to 15 mm for Multi-Link stents [Guidant, Santa Clara, California], Palmaz-Schatz stents [Johnson & Johnson, Warren, New Jersey), and NIR stents [Scimed, Maple Grove, Michigan], and up to 18 mm for InFlow stents [InFlow Dynamics, Munich, Germany]) had to be covered by 1 stent. Lesion exclusion criteria were diffuse disease, left main stenosis, and location in a restenotic, ostial, or bifurcated lesion. In 2 studies, stents of steel or gold surface were included. Ninety-nine ACS RX Multi-Link HP stents, 74 InFlow coronary steel stents, 73 InFlow gold stents, 41 Palmaz-Schatz stents, 12 NIR stainless steel stents, and 12 NIR Royale gold-surfaced stents were included. The ACS RX Multi-Link HP stent, the NIR 0002-9149/02/$–see front matter PII S0002-9149(02)02347-0

TABLE 1 Patient Demographics

Age (yrs) Men Diabetes mellitus Cigarette smoker Systemic hypertension Hyperlipidemia* Unstable angina

InFlow SS (n ⫽ 74)

InFlow Au (n ⫽ 73)

ML (n ⫽ 99)

PS (n ⫽ 41)

NIR SS (n ⫽ 12)

NIR Au (n ⫽ 12)

p Value

59 ⫾ 8 64 (86%) 14 (19%) 55 (74%) 47 (64%) 41 (56%) 14 (19%)

60 ⫾ 9 63 (86%) 8 (11%) 52 (71%) 34 (47%) 52 (71%) 13 (18%)

58 ⫾ 11 81 (82%) 21 (21%) 61 (62%) 53 (54%) 52 (53%) 21 (21%)

60 ⫾ 10 32 (78%) 12 (30%) 18 (45%) 27 (66%) 28 (68%) 7 (17%)

59 ⫾ 9 10 2 6 5 7 3

60 ⫾ 9 8 3 6 6 7 2

0.867 0.536 0.311 0.029 0.144 0.245 0.887

*Hyperlipidemia: serum cholesterol ⬎240 mg/dl or a history of elevated cholesterol requiring treatment. AU ⫽ gold surface; ML ⫽ Multi-Link; PS ⫽ Palmaz-Schatz; SS ⫽ stainless steel surface.

steel stent, and the NIR Royale stent were premounted on noncompliant high-pressure balloons. The InFlow steel and gold stents as well as the Palmaz-Schatz stent were manually crimped on a noncompliant highpressure balloon. The Multi-Link stent has a corrugated ring stent design. The NIR stents have a uniform cellular design. The InFlow and Palmaz-Schatz stents are tubular slotted stents. There were 259 men and 52 women in the study (mean age 59 ⫾ 10 years). The studies were approved by the institutional ethics committees and patients gave written informed consent for the studies. Stent length ranged from 9 to 18 mm based on the length of the coronary lesion. Stents were implanted according to standard protocols using an implantation pressure of ⱖ9 atm. Direct stenting was not part of any protocol. IVUS follow-up rates were 83% for the Multi-Link stents, 75% for the InFlow stents, 87% for the Palmaz-Schatz stents, and 81% for the NIR stents. Follow-up intervals were 5.7 ⫾ 1.3 months for the Multi-Link stents, 6.0 ⫾ 2.0 months for the InFlow stents, 6.4 ⫾ 1.2 months for the Palmaz-Schatz stents, and 6.1 ⫾ 1.2 months for the NIR stents (p ⫽ 0.114). Angiographic analysis: Cine angiograms were analyzed according to standard methods using a computer-assisted, automated, edge-detection algorithm (CAAS II System, PieMedical, Maastricht, The Netherlands).12 The external diameter of the contrast-filled catheter was the calibration standard; minimal lumen diameter and diameter stenosis were measured from the worst view. Intravascular ultrasound imaging and analysis: IVUS studies were performed using 2 commercially available systems: the Boston scientific system (Cardiovascular Imaging Systems, Sunnyvale, California) or the Endosonics system (Endosonics, Rancho Cordova, California). With both systems, the transducer was withdrawn automatically at 0.5 mm/s beginning approximately 10 mm beyond the stented lesion to perform an imaging sequence up to the aorto-ostial junction. IVUS studies were recorded on s-VHS tape for off-line analysis. Analysis of IVUS studies included cross-sectional area (CSA) measurements of the stent and lumen at 1-mm axial increments throughout the stent length. CSA measurements by IVUS have been validated.13 At the proximal and distal reference segments, only lumen CSA was measured. Area measurements were

performed with a commercially available program for computerized planimetry (TapeMeasure, Indec Systems, Capitola, California). If the neointimal tissue encompassed the imaging catheter, the lumen CSA was assumed to be the physical size of the imaging catheter (0.9 mm2). The following calculations were performed within the stent length: (1) IH CSA (mm2) ⫽ stent CSA ⫺ lumen CSA; (2) mean stent diameter (mm) ⫽ 2*公(stent CSA/␲); (3) mean lumen diameter (mm) ⫽ 2*公(lumen CSA/␲); and (4) mean IH thickness (mm) ⫽ (mean stent diameter ⫺ mean lumen diameter at follow-up)/2. The results for each stent were averaged over the stent length to obtain mean values. Statistical analysis: Statistical analysis was performed using SAS (Statistical Analysis Systems, SAS Institute, Inc., Cary, North Carolina). Continuous data are presented as mean ⫾ 1 SD. Categorical data are presented as frequencies. Comparisons between groups were performed using chi-square statistics and Fisher’s exact test for categorical variables, and paired and unpaired t tests for continuous variables. Factorial analysis of variance with Bonferroni’s correction (p ⬍0.0083 being significant for post hoc comparisons) was used to compare the 4 stainless steel stent designs. Univariate and multivariate regression analyses were used to identify predictors of IH thickness at follow-up. Variables included in the model were stent design, stent surface material, stent implantation pressure, maximal balloon diameter, age, gender, cardiovascular risk factors, reference vessel diameter, minimal lumen diameter before intervention, and mean stent CSA. Univariate parameters with significant impact (p value ⬍0.2) were entered into the multivariate model. A p value of 0.05 was considered statistically significant.

RESULTS Patient demographics are listed in Table 1. Analysis of the six stent types: Angiographic and procedural findings are shown in Table 2. NIR gold stents were implanted in slightly larger vessels than the other stent types and lesion length tended to be longer for NIR gold stents and Palmaz-Schatz stents than for the other stent types. Otherwise, there were no differences between the lesion characteristics of the applied 6 stent types. Palmaz-Schatz stents were implanted with higher pressure and larger balloons, indicating a more aggressive implantation technique

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TABLE 2 Angiographic and Procedural Data

Vessel LAD location Lesion length (mm) Preintervention Reference (mm) MLD (mm) DS (%) Postintervention MLD (mm) DS (%) Acute gain (mm) Impl. pressure (atm) Balloon diameter (mm) Stent length (mm) Follow-up MLD (mm) DS (%) Late loss (mm)

InFlow SS (n ⫽ 74)

InFlow Au (n ⫽ 73)

ML (n ⫽ 99)

46% 7.4 ⫾ 3.0

41% 7.2 ⫾ 2.7

39% 7.1 ⫾ 3.3

2.80 ⫾ 0.51 0.81 ⫾ 0.39 70 ⫾ 13

2.76 ⫾ 0.52 0.77 ⫾ 0.40 72 ⫾ 13

2.89 ⫾ 0.67 0.89 ⫾ 0.61 68 ⫾ 19

2.56 9 1.78 13.7 3.14 12.0

⫾ ⫾ ⫾ ⫾ ⫾ ⫾

0.42 11 0.61 2.5 0.35 3.7

1.70 ⫾ 0.71 30 ⫾ 24 1.13 ⫾ 0.64

2.66 3 1.86 12.9 3.22 13.3

⫾ ⫾ ⫾ ⫾ ⫾ ⫾

0.52 13 0.42 2.4 0.40 2.8

1.50 ⫾ 0.62 47 ⫾ 19 1.17 ⫾ 0.66

2.64 10 1.75 13.5 3.24 14.7

⫾ ⫾ ⫾ ⫾ ⫾ ⫾

0.63 16 0.62 3.3 0.35 1.6

1.80 ⫾ 0.80 32 ⫾ 36 0.84 ⫾ 0.76

PS (n ⫽ 41) 53% 10.5 ⫾ 3.5 3.02 ⫾ 0.48 0.89 ⫾ 0.46 70 ⫾ 32 3.07 0 2.15 14.9 3.41 14.0

⫾ ⫾ ⫾ ⫾ ⫾ ⫾

0.55 24 0.58 2.8 0.29 0.0

2.02 ⫾ 0.89 34 ⫾ 27 0.99 ⫾ 0.84

NIR SS (n ⫽ 12) 25% 9.0 ⫾ 3.1 2.92 ⫾ 0.74 0.99 ⫾ 0.27 63 ⫾ 9 2.78 1 1.79 14.9 3.33 14.8

⫾ ⫾ ⫾ ⫾ ⫾ ⫾

0.49 13 0.53 1.5 0.33 2.7

2.02 ⫾ 0.69 30 ⫾ 31 0.88 ⫾ 0.72

NIR Au (n ⫽ 12) 25% 10.1 ⫾ 3.6 3.31 ⫾ 0.82 1.21 ⫾ 0.45 62 ⫾ 13 3.29 2 2.08 13.3 3.29 11.9

⫾ ⫾ ⫾ ⫾ ⫾ ⫾

0.88 19 0.75 1.6 0.40 3.6

2.15 ⫾ 0.99 36 ⫾ 38 1.14 ⫾ 0.79

DS ⫽ diameter stenosis; Impl. ⫽ implantation; LAD ⫽ left anterior descending; MLD ⫽ minimal lumen diameter; other abbreviations as in Table 1.

TABLE 3 Intravascular Ultrasound Measurements at Follow-up InFlow SS (n ⫽ 74) Reference lumen CSA (mm2) Stent CSA (mm2) Stent/reference lumen CSA IH CSA (mm2) IH thickness (mm)

8.5 7.9 0.93 3.1 0.36

⫾ ⫾ ⫾ ⫾ ⫾

2.6 2.1 0.28 1.2 0.13

InFlow Au (n ⫽ 73) 8.4 8.1 0.96 3.7 0.43

⫾ ⫾ ⫾ ⫾ ⫾

2.7 2.7 0.31 1.3 0.14

ML (n ⫽ 99) 8.6 7.8 0.91 1.8 0.20

⫾ ⫾ ⫾ ⫾ ⫾

3.1 2.3 0.30 1.1 0.13

PS (n ⫽ 41) 9.0 9.0 1.0 2.6 0.26

⫾ ⫾ ⫾ ⫾ ⫾

2.6 1.7 0.25 1.5 0.19

NIR SS (n ⫽ 12) 8.8 8.6 0.98 2.9 0.31

⫾ ⫾ ⫾ ⫾ ⫾

2.6 2.0 0.28 0.7 0.07

NIR Au (n ⫽ 12) 10.2 9.0 0.88 3.4 0.35

⫾ ⫾ ⫾ ⫾ ⫾

3.1 2.9 0.26 1.1 0.08

Abbreviations as in Table 1.

than for the other stent types. Subsequently, acute gain was larger for Palmaz-Schatz stents, resulting in greater stent CSA (Table 3). Late loss ranged from 0.84 ⫾ 0.76 to 1.17 ⫾ 0.66 mm (p ⫽ 0.131). Mean IH CSA ranged from 1.8 ⫾ 1.1 to 3.7 ⫾ 1.3 mm2 between the stent types (p ⬍0.001). Similarly, mean IH thickness ranged from 0.20 ⫾ 0.11 mm for the MultiLink steel stent to 0.43 ⫾ 0.14 mm for the InFlow gold stent (p ⬍0.001). Stainless steel stents: There was no difference in late lumen loss between the 4 steel stent designs (Table 2). Follow-up diameter stenosis was similar among the groups (p ⫽ 0.253). Mean IH CSA varied with stent design (p ⬍0.001). It was significantly less in MultiLink stents than in each of the other 3 types, but similar in InFlow, Palmaz-Schatz, and NIR stents (Table 3). Mean IH thickness also varied among the designs from 0.20 ⫾ 0.13 mm for the Multi-Link to 0.36 ⫾ 0.13 mm for the InFlow stent (p ⬍0.001) (Figure 1). Gold surfacing: When InFlow gold and NIR gold stents were compared with InFlow steel and NIR steel stents, reference artery diameter, minimal lumen diameter before intervention, lesion length, stent length, and balloon diameter for stent implantation were similar (Table 2). Implantation pressures were lower for the goldcoated stents (p ⫽ 0.012). Final minimal lumen diameter was similar. There was a trend for a greater late loss index for gold stents (0.62 ⫾ 0.35 vs 0.51 ⫾ 0.44, p ⫽ 1362 THE AMERICAN JOURNAL OF CARDIOLOGY姞

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0.086). IVUS analysis (Table 3) showed that mean stent CSA for gold stents was similar to steel stents (p ⫽ 0.445). Mean IH CSA at follow-up was greater in goldsurfaced stents (3.6 ⫾ 1.3 vs 3.1 ⫾ 1.1 mm2; p ⫽ 0.006). Similarly, mean IH thickness was 20% greater for the InFlow gold stent compared with the InFlow steel stent, and 13% greater for the NIR gold stent compared with the NIR steel stent (both stent types together 0.42 ⫾ 0.14 vs 0.35 ⫾ 0.13 mm, p ⫽ 0.002). Considering only InFlow stents, IVUS analysis showed that mean stent CSA was similar between the InFlow steel stents and the InFlow gold stents, but mean IH CSA and thickness were greater in gold-surfaced stents (p ⫽ 0.005 and p ⫽ 0.001, respectively). Predictors of intimal hyperplasia: Univariate predictors of IH thickness were stent design, stent coating, and diabetes. Logistic regression analysis demonstrated InFlow stent design and gold coating to be univariate predictors for IH thickness ⬎0.3 mm. Multivariate analysis confirmed non–Multi-Link stent design, stent coating, and diabetes to be the only independent predictors of IH thickness (Table 4). In a multivariate logistic regression analysis, non–MultiLink stent design and gold coating were predictors of IH thickness of ⬎0.3 mm (Table 4).

DISCUSSION This IVUS study on 4 different stent designs and 2 different stent surface materials indicates that stent JUNE 15, 2002

There are only a limited number of clinical stent restenosis studies with direct comparison of different stent types. These studies have provided inconsistent results regarding the impact of stent design on restenosis in the clinical setting of human atherosclerotic coronary arteries. Several clinical trials demonstrated equivalency between different stents designs on binary restenosis rates, minimal lumen diameter at follow-up, and late loss.18,19 This has fueled uncertainty as to whether results of experimental animal restenosis models with controlled vascular injury induced to a nondiseased vessel may be translated to the complex human coronary lesion. It has only been reFIGURE 1. Mean (ⴞ SD) IH thickness for the different stent types. cently that differences in angiographic restenosis rates have been reported between different stent types. In 1 study of 4,510 patients, TABLE 4 Independent Predictors of Intimal Hyperplasia (IH) Thickness the angiographic restenosis rate after IH Thickness ⬎0.3 mm IH Thickness placement of stents was found to be 2 dependent on the inserted stent OR (95% CI) p value R p Value type.20 However, this study did not Non–Multi-Link Stent Design 3.45 (1.13–11.11) 0.034 0.019 0.014 control for similar lesion types beGold coating 3.78 (1.88–7.54) ⬍0.001 0.144 ⬍0.001 tween the analyzed stent types. An Diabetes mellitus — — 0.014 0.041 angiographic study comparing 2 CI ⫽ confidence interval; OR ⫽ odds ratio. stents of similar design but different strut thickness confirmed an increasing restenosis rate with greater strut design, stent surface material, and diabetes mellitus thickness, as suggested from histologic studies.21 Simhave an important impact on the amount of IH thick- ilarly, a gold-coated stent was shown to have an ness after coronary stent placement. increased restenosis rate compared with a steel stent of Predictors of restenosis: There are several studies similar design.10 In a study on 755 patients, the Githat have evaluated patient, lesion, and procedure- anturco-Roubin II (GR II) stent was shown to have a related predictors of angiographic restenosis after higher restenosis rate than the Palmaz-Schatz stent.22 stent placement.4,5,14 In these studies, diabetes melli- In that study, differences between the GR-II and the tus, lesion length, lesion plaque burden, number of Palmaz-Schatz stent were contributed mainly to stents, acute lumen gain, and the final obtained lumen greater acute stent recoil and increased tissue prolapse diameter were found to have an important impact on for the GR-II stent, resulting in different acute results. the binary angiographic restenosis rate. Because the This IVUS study demonstrates that IH is deterPalmaz-Schatz stent was the predominantly included mined by stent design and stent surface material. stent in early stent restenosis studies, stent design and These factors had a greater impact than previously surface material have not been analyzed as factors described clinical and lesion-related predictors of rewith impact on stent restenosis. With the availability stenosis. The Multi-Link stent was found to induce the of more stent types, the importance of stent design and smallest IH thickness. The Multi-Link stent combines surface material for subsequent IH and restenosis has a thin strut thickness with a corrugated-ring stent gained greater interest. design. Both factors have been demonstrated to be In animal restenosis models, the significant impact associated with less vessel trauma and subsequent IH. of stent design on the stent-vessel interaction and Absolute differences in IH thickness between the andegree of vessel injury has been demonstrated.7–9,15,16 alyzed stents were small compared with the lumen The stent design was shown to determine endothelial dimensions achieved within the stents despite the denudation during stent expansion and the depth of great relative differences. This indicates that the bistent strut incision. Vessel injury was found to be nary angiographic restenosis rate is a rather insensitive determined by strut thickness, the number of struts per parameter to determine differences in IH proliferation cross section, and stents with a tubular-slotted or cor- induced by different stent types. rugated-ring design.8,16 Greater arterial injury is Impact of gold coating on intimal hyperplasia: The known to induce a pronounced inflammatory reaction greater IH found for gold-coated InFlow stents comand subsequently more IH.15,17 pared with InFlow steel stents agrees with a recent CORONARY ARTERY DISEASE/PREDICTORS OF INTIMAL HYPERPLASIA

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angiographic study.10 However, this present study extends the observation beyond the InFlow Gold stent. Although the number of NIR stents included in this study was small, there was a similar trend for increased IH thickness when comparing the NIR goldcoated stent with the NIR steel stent. Previous histologic studies on the porcine coronary artery model have confirmed for NIR stents that gold-coating enhances IH unless special heating procedures are performed to improve surface finish.23 1. Fishman D, Leon M, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri

L, Ricci D, Nobuyoshi M. A randomized comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994;331:496 –501. 2. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrichx G, Emanuelsson H, Marco J, Legrand V, Materne P. A comparison of balloon expandable stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994;331:489 –495. 3. Hoffmann R, Mintz GS, Dussaillant RG, Popma JJ, Pichard AD, Satler LF, Kent KM, Griffin J, Leon MB. Patterns and mechanisms of instent restenosis: a serial intravascular ultrasound study. Circulation 1996;94:1247–1254. 4. Kasaoka S, Tobis JM, Akiyama T, Reimers B, Di Mario C, Wong ND, Colombo A. Angiographic and intravascular ultrasound predictors of in-stent restenosis. J Am Coll Cardiol 1998;32:1630 –1635. 5. Bauters C, Hubert E, Prat A, Bougrimi K, van Belle E, McFadden EP, Amouyel P, Lablanche JM, Bertrand M. Predictors of restenosis after coronary stent implantation. J Am Coll Cardiol 1998;31:1291–1298. 6. Hoffmann R, Mintz GS, Mehran R, Popma JJ, Pichard AD, Kent KM, Satler LF, Hongshen W, Leon MB. Intravascular ultrasound predictors of angiographic restenosis in lesions treated with Palmaz-Schatz Stents. J Am Coll Cardiol 1998;31:43–49. 7. Barth KH, Virmani R, Froelich J, Takeda T, Lossef SV, Newsome J, Jones R, Lindisch D. Paired comparison of vascular wall reactions to Palmaz stents, Strecker tantalum stents, and Wallstents in canine iliac and femoral arteries. Circulation 1996;93:2161–2169. 8. Rogers C, Edelman ER. Endovascular stent design dictates experimental restenosis and thrombosis. Circulation 1995;91:2995–3001. 9. Garasic JM, Edelman ER, Squire JC, Seifert P, Williams MS, Rogers C. Stent and artery geometry determine intimal thickening independent of arterial injury. Circulation 2000;101:812–818. 10. Kastrati A, Scho¨ mig A, Dirschinger J, Mehilli J, von Welser N, Pache J,

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