Drug-Eluting Stent Strut Distribution: A Comparison between Cypher™ and Taxus® by Optical Coherence Tomography
March 2006
Recent studies have shown that the use of drug-eluting stents (DES) to deliver antiproliferative agents directly to the vessel wall dramatically reduces the rate of restenosis. However, differences among stent designs, drug delivery vehicles, and choices of pharmacologic agents can significantly affect the safety and efficacy of each device. Thus, focused study on the various constituents of delivery platforms, including the stent backbone, materials used as drug delivery vehicles and the physicochemical properties of the pharmacotherapeutic agents themselves is indicated.1,2 In addition, several clinical trials compared the Taxus®(Boston Scientific Corp., Natick, Massachusetts) and Cypher™ (Cordis Corp., Miami, Florida) stents, showing a difference in neointimal proliferation between these two devices, and suggesting that the drug delivery platform may account for this difference.3–8
Furthermore, a previous study using intravascular ultrasound (IVUS) demonstrated that the number and distribution of stent struts affect the amount of neointimal formation after sirolimus-eluting stent implantation.9 However, conventional IVUS provides a limited definition of vessel microstructure, such as dissection, tissue prolapse, stent strut and stent apposition on a size scale 10–12
Thus, the purpose of this study is to compare the stent strut distribution between various stent designs using OCT in a phantom model.
Materials and Methods
We developed an experimental model made of silicon tubing (inner diameter of 3 mm) angled at 0°, 30° and 60°. Testing was performed on the Cypher and Taxus stents which represent current FDA-approved DES systems, respectively. Each stent size used in this study was 3.0 mm. At the center of the phantom, all stents were deployed at nominal pressure.
After stent deployment, OCT was performed using the LightLab OCT imaging system, and a 0.014 inch Imagewire with 0.006 inch Micro-Optic core (LightLab, Westford, Massachusetts). The OCT Imagewire was advanced beyond the stent into the distal site of the phantom and withdrawn to the proximal site. OCT images were acquired at a frame rate of 15.6 Hz at 0.5 mm/second with an automatic pullback system, and were digitally archived. These procedures were performed in each stent three separate times.
Measurements were performed at two cross sections: maximum and minimum number of visualized stent strut sites (defined as max site and min site, respectively) within 3 mm from the center of the stent. At each cross section, the following were obtained: (1) number of visualized stent struts; (2) angle between stent struts (interstrut angle); (3) mean interstrut angle; (4) the delta mean angle was defined as the margin between each value of interstrut angle and mean interstrut angle (Figure 1).
Interobserver and intraobserver variabilities were assessed for all images and all measurements. Interobserver variability was calculated as the standard deviation of the difference between the measurements of the two independent observers and expressed as a percentage of the average value. Intraobserver variability was calculated as the standard deviation of the difference between the first and second determinations (a one-week interval) for a single observer, and expressed as a percentage of the average value. Interobserver and intraobserver variabilities for the measurement of the number of visualized stent struts were 0.7% and 1.2%, respectively; for measurement of the interstrut angle, they were 3.7% and 4.3%, respectively.
Statistical Analysis. Statistical analysis was performed using SPSS 13.0 software (SPSS Inc.). Data are presented as frequencies or mean ± standard deviation (SD). A p-value p p 1,2 Hwang and colleagues evaluated the impact of cell design and drug properties on drug delivery using Palmaz-Schatz® Crown stents (Cordis Corp.) in an in vivo model using bovine carotid arteries and a computational model. The results of their investigations challenged the prevailing view that DES delivered the drug and bathed the artery homogeneously, allowing complete drug delivery and saturation of the entire vessel wall. They found that even at steady-state conditions, sodium fluorescein delivered from the surface of the stent was visible in blood vessels in a pattern that directly represented the stent strut pattern.13
In the large clinical trials, the sirolimus-eluting balloon-expandable stent in the treatment of patients with de novo native coronary artery lesions (SIRIUS) and the international paclitaxel-eluting NIR® stent in the treatment of de novo lesions (TAXUS-II), restenotic lesions were frequently located near the stent margins or at the site of a gap between stents (64.5% in SIRIUS; 50.0% in TAXUS-II).14,15
Takebayashi and colleagues reported that maximum neointimal hyperplasia (IH) thickness occurred at the site of the maximal interstrut angle in 82% of sirolimus-eluting stents, along with a significant positive correlation between the IH cross-sectional area, IH thickness and the maximum interstrut angle.9 In addition, the meta-analysis of the various trials showed patients who received Cypher stents had a 36% reduction in the odds of target lesion revascularization, and a 32% reduction in the odds of angiographic restenosis compared with Taxus stents.7
These results demonstrate the following: (1) nonuniform stent strut distribution, such as a gap between stents and the stent edge, may be associated with a decrease in local drug delivery and may then cause restenosis; (2) the stent-strut configuration directly serves to determine the pattern and degree of drug delivery achieved by the stent; (3) optimal drug delivery requires symmetric expansion of stents with optical axial distribution of struts. Furthermore, factors such as the difference in the mechanism of drug action and the difference in coating materials may influence their local pharmacological effects. Sirolimus is an immunosuppressive drug with anti-inflammatory properties and is regarded as a cytostatic agent, while paclitaxel is an antineoplastic drug and is regarded as a cytotoxic agent.2,16,17 Although the polymer coating of the sirolimus-eluting stent allows for elution of 100% of the drug, most of which occurs within 1 month, the polymer coating of the paclitaxel-eluting stent allows for elution of only 10% of the drug over 2 months, with 90% of the paclitaxel agent remaining sequestered in the polymer indefinitely.18
The present study assigned a focus to the stent design and evaluated them by OCT, which may be approved by FDA in near future. It found that the stent strut distribution of two stents, Cypher and Taxus, the current FDA-approved drug-eluting systems, were significantly different. Although the numbers of visualized stent struts were similar, maximum interstrut angle and the delta mean angle of the Cypher stent were significantly smaller at both cross sections. These results demonstrated that the strut distribution of the Cypher stent was maintained more regularly among these stents. Interestingly, on the Taxus stent, although the change of maximum interstrut angle between the phantom angle 0° and 30° at the max site was minimal, it was larger at the min site. As for the curvature in the range of 0–30°, this range seems the to be the most common among lesions in the “real world” treated by percutaneous coronary intervention procedures. Stents have been categorized as closed-cell stents, open-cell stents and ring stents. Closed-cell stents retain the same area within any given stent cell, regardless of how stretched or compressed the stent becomes in the settings of curvature or lesion eccentricity. Open-cell stents are those in which the area enclosed by a single strut can vary greatly, meaning that the area may be quite small on the inner aspect of a curve, and much larger on the outer aspect of the curve. These characteristics of open-cell stents may have caused the results seen with the Taxus stent. The architectural features of the stent mentioned above may influence procedural deliverability, conformability, procedural success and the rate of restenosis in the BMS era, but no longer will these be the goal of stent design.
In the DES era, in addition to the physicochemical properties of the drug, geometric characteristics of the delivery device must be considered. Optimization of drug distribution therefore requires symmetric expansion of stents with optical axial distribution of struts.13
From the perspective of stent design, our observations by OCT suggest that stent designs that maintain regular strut distribution, despite expansion in various anatomical circumstances (for example, tortuous segments, bifurcations and ostial locations), will provide the most regular and predictable drug delivery.
Conclusions
There were significant differences in stent strut distribution between the two current FDA-approved drug-eluting stent systems studied (Cypher and Taxus). This study suggests that the Cypher stent maintains regular strut distribution despite expansion in various anatomical situations and appears to provide more regular and predictable drug delivery.
Study limitations. Any bench-top testing is intrinsically limited because it can never precisely reproduce in vivo conditions. Unfortunately, we have not yet evaluated clinical cases using OCT.
Acknowledgements. This study received the support from device manufacturers that donated OCT catheters and stents for testing. We also thank Heidi Bonneau, RN, MS, for her editorial review of this manuscript.
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