Drug Eluting Stent Implantation for High Risk Patients and Novel Technologies in Percutaneous Coronary Intervention

Percutaneous coronary intervention is a major treatment strategy for patients with coronary artery disease, and currently coronary stents are widely used in the world.1 Although stent implantation itself has shown to reduce restenosis by preventing both early elastic recoil and late vascular remodeling compared to balloon angioplasty, in-stent restenosis (ISR) still occurs in 10-40% of patients and has been the ‘Achilles’ heel’ of coronary interventions, frequently resulting in repeated revascularization.2,3 Restenosis after coronary stenting occurs secondary to the accumulation of smooth muscle cells and extracellular matrix proteoglycans.4 Despite the sophistication of the new techniques and enormous advance in devices, ISR requiring repeat procedure has been considered as a main limitation of coronary stenting. The advent of drug eluting stents (DES), which consist of a drug (immunosuppressive or antiproliferative drug), a polymer and a metallic platform, has revolutionized the practice of interventional cardiology by significantly reducing the rates of restenosis and repeat revascularization as compared to bare metal stents.5 After the first approval of DES, a large number of patients with coronary artery disease have undergone percutaneous revascularization with DES. However, many trials conducted in the ‘real world’ showed that the problem of restenosis was not completely resolved and still persists. Effect of DES for patients at high risk for ISR, such as acute myocardial infarction, small coronary vessels, aorto-ostial lesions, or lesions of chronic total occlusion (Part 1 of this thesis), have not been fully investigated. In addition, certain potential safety concerns regarding the widespread use of DES have arisen. The most notable drawback of DES is that they could increase the risk of thrombotic complication, especially late stent thrombosis6, although its incidence is low.7 The increased risk of thrombosis with DES utilization may be associated with altered endothelial function8 and/or delayed vascular healing9 induced by cytotoxic and cytostatic drug use. Localized hypersensitivity reactions to the polymer coating of DES and drug itself may also contribute to stent thrombosis.10 To retain the positive clinical aspects of DES and overcome their drawbacks, new concept stents have been developed (Part 2 of this thesis)

Late Stent Recoil of the Bioabsorbable Everolimus-Eluting Coronary Stent and its Relationship With Plaque Morphology

Objectives This study sought to evaluate late recoil of a novel bioabsorbable everolimus-eluting coronary stent (BVS), which is composed of a poly-L-lactic acid backbone, coated with a bioabsorbable polymer containing everolimus. Background Little is known about the mechanical behavior of bioabsorbable polymer stents after deployment in diseased human coronary arteries. Methods The study population consisted of 16 patients, who were treated with elective BVS implantation for single de novo native coronary artery lesions and were followed at 6 months. All patients underwent an intravascular ultrasound examination at post-procedure and follow-up. A total of 484 paired cross-sectional areas (CSAs) were acquired and analyzed. Late absolute stent recoil was defined as stent area at post-procedure ( X) - stent area at follow-up (Y). Late percent stent recoil was defined as (X - Y)/X X 100. In each CSA, plaque morphology was assessed qualitatively and classified as calcific, fibronecrotic, or fibrocellular plaque. Results Late absolute and percent recoil of the BVS was 0.65 +/- 1.71 mm(2) (95% confidence interval [CI]: 0.49 to 0.80 mm(2)) and 7.60 +/- 23.3% (95% CI: 5.52% to 9.68%). Calcified plaques resulted in significantly less late recoil (0.20 +/- 1.54 mm(2) and 1.97 +/- 22.2%) than fibronecrotic plaques (1.03 +/- 2.12 mm(2) and 12.4 +/- 28.0%, p = 0.001 and p = 0.001, respectively) or fibrocellular plaque (0.74 +/- 1.48 mm(2) and 8.90 +/- 19.8%, p = 0.001 and p = 0.001, respectively). Conclusions The BVS shrank in size during the follow-up period. The lesion morphology of stented segments might affect the degree of late recoil of the BVS. ( ABSORB Everolimus Eluting Coronary Stent System First in Man Clinical Investigation; NCT00300131) (J Am Coll Cardiol 2008; 52: 1616 - 20) (c) 2008 by the American College of Cardiology Foundatio

Characterization of edge effects with paclitaxel-eluting stents using serial intravascular ultrasound radiofrequency data analysis: The BETAX (BEside TAXus) study

Introduction and objectives. At present, the effect of paclitaxel on tissue structure at the edges of Taxus® stents is unknown. The objective of this study was to investigate in vivo the temporal changes occurring at the edges of paclitaxel-eluting stents using intravascular ultrasound radiofrequency (IVUS-RF) data analysis. Methods. The study included 24 patients who had a total of 26 paclitaxel-eluting stented segments. In all patients, IVUS-RF imaging was performed 5 mm proximally and 5 mm distally to the stent edges 6 months after stent implantation. For subsequent analysis, proximal and distal segments were divided into five 1-mm subsegments. Results. In the first two subsegments adjacent to the proximal edge of the stent, the vessel wall had grown to compensate for plaque growth without affecting the vessel lumen, while in the remaining three subsegments there was overcompensation (i.e., the vessel wall increased to greater than the plaque size). Consequently, the lumen had increased in size. At the distal edge of the stent, overcompensation was observed in all five subsegments and the lumen had increased in size. In general, proximal and distal growth was due to an increase in fibrolipid plaque (P<.001 and P<.001, respectively) along with a decrease in the necrotic core (P=.014 and P<.001, respectively) and the presence of dense calcium (P<.001 and P<.001, respectively). Conclusions. Serial expansive vascular remodeling was observed at proximal and distal stent edges. Remodeling occurred in response to tissue growth, which was mainly due to increased fibrofatty tissue