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)

Update on stents: Recent studies on the TAXUS® stent system in small vessels

Small vessel size (<3 mm) has been identified as an independent predictive factor of restenosis after percutaneous coronary intervention when using bare metal stents (BMS). It remains controversial whether BMS placement in small vessels has an advantage over balloon angioplasty in terms of angiographic and clinical outcomes. The advent of drug eluting stents (DES), either paclitaxel-eluting stents (PES) or sirolimus-eluting stents (SES), has strongly impacted interventional cardiology by significantly reducing restenosis and the need for repeat revascularization. Therefore, it was also expected that DES could substantially reduce restenosis in smaller vessels. However, even in the DES era, small vessel size remains an independent predictor of angiographic and clinical restenosis. To date, only a few studies systematically investigate the clinical effect of DES placement in small vessels. In addition, some potential issues with the use of DES have been raised, such as late stent thrombosis and late restenosis. In order to (i) establish the superiority of DES over BMS; (ii) verify the efficacy and safety of DES; and (iii) critically assess the superiority of one DES over the other in patients with small coronary arteries, further multicenter, randomized clinical trials with larger sample size are warranted

Effect of olmesartan on the levels of circulating endothelial progenitor cell after drug-eluting stent implantation in patients receiving statin therapy

AbstractBackgroundThe endothelial progenitor cell (EPC) plays an important role in repairing vascular injury. Statins and angiotensin II receptor blockers increase the level of circulating EPCs. However, it is unknown whether the angiotensin II receptor blocker olmesartan synergistically acts with statins to increase the levels of circulating EPCs. Moreover, the association between the levels of circulating EPCs and endothelial dysfunction after implantation of drug-eluting stents (DESs) has not been evaluated.MethodsNine patients with stable coronary artery disease underwent percutaneous coronary intervention (PCI) and received DES implantation. All patients received olmesartan in addition to statin therapy after PCI. The dose of olmesartan was based on the physician's discretion as per the patients’ blood pressure. The levels of circulating EPCs were analyzed at baseline, post-PCI, and 1, 2, 3, and 8 months after PCI. Coronary angiography and the acetylcholine provocation test were performed on all patients at 8 months.ResultsAlthough the angiotensin II level significantly changed, the levels of circulating EPCs did not change during 8 months of olmesartan treatment (3.1±0.6cells/ml, 2.5±0.8cells/ml, 2.0±0.6cells/ml, 2.9±0.9cells/ml, 3.0±0.4cells/ml, 3.4±0.8cells/ml, p=0.64). The patients were subsequently divided into two groups based on whether the level of circulating EPCs was less or greater than 4cells/ml at 8 months. There were no significant differences in the mean vessel diameter of each segment (proximal, proximal edge, distal edge, and distal) after the acetylcholine provocation test between the two groups.ConclusionsLow-to-moderate doses of olmesartan might not increase the level of circulating EPCs in patients receiving statin therapy. There might be no association between the levels of circulating EPCs and the degree of coronary vasospasm in the acetylcholine provocation test 8 months after DES implantation

Update on stents: Recent studies on the TAXUS&reg; stent system in small vessels

Shuzou Tanimoto, Joost Daemen, Patrick W SerruysThoraxcenter, Erasmus Medical Center, Rotterdam, The NetherlandsAbstract: Small vessel size (&lt;3 mm) has been identified as an independent predictive factor of restenosis after percutaneous coronary intervention when using bare metal stents (BMS). It remains controversial whether BMS placement in small vessels has an advantage over balloon angioplasty in terms of angiographic and clinical outcomes. The advent of drug eluting stents (DES), either paclitaxel-eluting stents (PES) or sirolimus-eluting stents (SES), has strongly impacted interventional cardiology by significantly reducing restenosis and the need for repeat revascularization. Therefore, it was also expected that DES could substantially reduce restenosis in smaller vessels. However, even in the DES era, small vessel size remains an independent predictor of angiographic and clinical restenosis. To date, only a few studies systematically investigate the clinical effect of DES placement in small vessels. In addition, some potential issues with the use of DES have been raised, such as late stent thrombosis and late restenosis. In order to (i) establish the superiority of DES over BMS; (ii) verify the efficacy and safety of DES; and (iii) critically assess the superiority of one DES over the other in patients with small coronary arteries, further multicenter, randomized clinical trials with larger sample size are warranted.Keywords: paclitaxel, stent, coronary artery disease, restenosi

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