Dexamethasone-eluting Stents Research Articles

In vitro hemocompatibility and cytocompatibility of dexamethasone-eluting PLGA stent coatings

Drug-eluting stents (DESs) have been an important breakthrough for interventional cardiology applications since 2002. Though successful in reducing restenosis, some adverse clinical problems still emerged, which were mostly caused by the bare-metal stents and non-biodegradable polymer coatings, associated with the delayed endothelialization process. In this study, dexamethasone-loaded poly (lactic-co-glycolic acid) (PLGA) coatings were developed to explore the potential application of dexamethasone-eluting stents. Dexamethasone-eluting PLGA stents were prepared using ultrasonic atomization spray method. For other tests like stability and cytocompatibility and hemocompatibility tests, dexamethasone loaded coatings were deposited on 316L SS wafers. Fourier transform-infrared spectroscopy (FT-IR) results demonstrated that there was no chemical reaction between PLGA and dexamethasone. The balloon expansion experiment and surface morphology observation suggested that the stent coatings were smooth and uniform, and could also withstand the compressive and tensile strains imparted without cracking after stent expansion. The drug release behavior in vitro indicated that dexamethasone existed burst release within 1 day, but it presented linear release characteristics after 6 days. In vitro platelets adhesion, activation test and APTT test were also done, which showed that after blending dexamethasone into PLGA, the hemocompatibility was improved. Besides, dexamethasone and dexamethasone-loaded PLGA coatings could significantly inhibit the attachment and proliferation of smooth muscle cells.

Dexamethasone‐eluting Vascular Stents

Percutaneous transluminal angioplasty (PTA) with stenting is widely used in the treatment of vascular disorders, but restenosis remains a significant problem. Drug-eluting stents (DES) have been developed as an attempt to reduce the intimal response leading to restenosis. Drugs used in DES include mainly immunosuppressive and anti-proliferative compounds. Glucocorticoids are also an interesting possibility for those purposes because they have anti-proliferative effects in vascular smooth muscle cells and down-regulate the production of cytokines and growth factors driving inflammation and fibrosis. In this MiniReview, feasibility and safety of drug-eluting metal and biodegradable vascular stents are discussed with special emphasis on dexamethasone-eluting stents.

Dexamethasone-eluting stents had sustained favorable ischemic driven target lesion revascularization rates over 5 years: A randomized controlled prospective study

Dexamethasone-eluting stents had sustained favorable ischemic driven target lesion revascularization rates over 5 years: A randomized controlled prospective study

Urethral in situ biocompatibility of new drug‐eluting biodegradable stents: an experimental study in the rabbit

To assess the effect of drug-eluting properties on the degradation process and the biocompatibility of biodegradable drug-eluting urethral stents. Braided biodegradable 80 L/20D-PLGA (copolymer of polylactide and polyglycolide) stents with drug-eluting properties were used as the test material. The drugs analysed were indomethacin, dexamethasone and ciprofloxacine. 80 L/20D-PLGA stents without a drug coating served as controls. In all, 16 male rabbits were used and divided into four groups. The stents were inserted under general anaesthesia into the posterior urethra. After 1 month, the rabbits were killed and the urethra removed for histological and optic microscopy analyses. Control stents and the dexamethasone-eluting stents degraded totally during the follow-up period. Conversely, in both indomethacin- and ciprofloxacine-eluting stent groups, the degradation process was significantly delayed and they induced an increase in epithelial hyperplasia. Histological analysis showed that all the stents induced eosinophilia, but there were no significant differences in the intensity of acute or chronic inflammatory reactions and fibrosis. A drug-eluting capacity can be added to biodegradable stents. The addition of a drug influences the biodegradation time of PLGA urethral stents. Further studies are needed, to find the proper concentrations and releasing profiles of the drugs to achieve the desired bioactivity and biocompatibility properties.

Coating preparation and drug delayed release in vitro and in vivo of dexamethasone‐eluting intravascular stents

Coating preparation and drug delayed release <i>in vitro</i> and <i>in vivo</i> of dexamethasone‐eluting intravascular stents

Randomized comparison of dexamethasone-eluting stents with bare metal stent implantation in patients with acute coronary syndrome: Serial angiographic and sonographic analysis

The aim of this study is to compare the anti-inflammatory effect of the dexamethasone preloaded stent (Dexamet, Abbott, Galway, Ireland) with the bare metal stent (BMS; BiodivYsio, Biocompatibles Cardiovascular LTD, Galway, Ireland) in patients with acute coronary syndrome (ACS) assessed by angiographic (QCA) and intracoronary ultrasound (ICUS). One hundred twenty patients with ACS were randomly assigned to revascularization using the Dexamet stent (n = 60) or BMS (n = 60). Serial QCA analysis and ICUS analysis were performed during long-term follow-up (2.9 F; 20 MHz transducer; Volcano Corp, Brussels, Belgium). Power calculations were performed for QCA-derived differences of lumen loss. In addition, statistical analysis was performed (SPSS for Windows 12.0.1). The target lesion revascularization rate was lower in the Dexamet group (10 [16.67%] vs 20 [33.33%] patients; P = .031). The QCA revealed improved lumen restoration in the Dexamet stent group (lumen loss, 0.55 +/- 0.65 vs 1.07 +/- 0.92 mm [P = .001]; loss index, 0.20 +/- 0.23 vs 0.46 +/- 0.42 [P < .001]). The ICUS revealed greater neointimal proliferation in the BMS versus the Dexamet stent group (3.36 +/- 1.03 vs 3.05 +/- 1.38 mm2; P < .001). Death (n = 1) and the number of total occlusions of the stent segment (n = 1) were identical in both groups. Dexamet stents, in comparison with the BMS stents, reduced the target lesion revascularization rate in patients with ACS and lead to better lumen restoration during long-term follow-up.

Dexamethasone-eluting stents for the prevention of in-stent restenosis: Evidence for a differential effect in insulin-dependent and non-insulin-dependent diabetic patients

Diabetes mellitus (DM) is a strong predictor of in-stent restenosis. This may be due to a higher level of vascular inflammation. We hypothesized that diabetic patients will benefit from dexamethasone-eluting stents, since local inflammation and consequently neointimal growth are suppressed and no systemic side effects will occur. Methods 21 consecutive patients with DM with 32 lesions were treated with dexamethasone-eluting stents. Excluded were patients with triple vessel disease, bifurcation lesions, previous revascularization of the culprit vessel, and reference diameter smaller than 2.5 or larger than 3.75 mm. MACE (death, myocardial infarction, and revascularization) was counted at 12 months. At 6 months, angiographic follow-up was performed. Results Of the patients, 38% had insulin-dependent DM. Lesion type was type A/B1 in 56% and B2/C in 44%. Lesion length was 15.7 ± 8.4 mm and the reference diameter was 2.83 ± 0.53 mm. Event-free survival at 12 months was 62%. Any revascularization procedure was performed in 33% and target lesion revascularization in 24% of the patients. At 6 months in-stent late loss was 1.07 ± 0.64 mm. Binary restenosis occurred in 28.1% of the lesions. The event-free survival in insulin-dependent DM was worse compared to non-insulin-dependent DM (92.1 vs. 37.8%; p < 0.01). Patients with insulin-dependent DM had higher in-stent late loss compared to non-insulin-dependent DM patients (1.44 ± 0.83 vs. 0.83 ± 0.51 mm; p < 0.01). Conclusion Treatment with dexamethasone-eluting stents in patients with DM is associated with a relatively high restenosis rate. Our data suggest a differential effect of dexamethasone-eluting stents in insulin-dependent compared to non-insulin-dependent DM.

The favorable clinical and angiographic outcomes of a high-dose dexamethasone-eluting stent: Randomized controlled prospective study

Previous studies with dexamethasone-eluting stents could not elucidate the role of dexamethasone in the prevention of neointimal hyperplasia because they did not compare their results with a control group. We prospectively evaluated the clinical and angiographic outcomes of dexamethasone-eluting stents, comparing them with unloaded stents of an identical design. A total of 92 patients (98 lesions) were randomly assigned to the dexamethasone group (67 patients, 71 lesions) or control group (25 patients, 27 lesions). The inclusion criteria for a stent implantation were a de novo lesion with a diameter of 2.60 to 4.0 mm. BiodivYsio Drug Delivery phosphorylcholine-coated stents (Biocompatibles Ltd, Galway, Ireland) were immersed in a 20-mg/mL dexamethasone solution, yielding a total dexamethasone dose of 0.5 microg/mm2 per stent. The total major adverse cardiac events rate at 12 months was significantly lower in the dexamethasone group, as compared with the control group (10.4% [7/67] vs 28.0% [7/25], P = .037). The binary restenosis rate at 6 months was 11.9% (7/59) in the dexamethasone group and 42.9% (9/21) in the control group (P = .002). The use of dexamethasone-eluting stents was the only independent predictor for the major adverse cardiac event at 12 months (relative risk 0.20, 95% CI 0.06-0.68, P = .009) and binary restenosis at 6 months (relative risk 0.17, 95% CI 0.05-0.60, P = .006) by multivariate analysis. Dexamethasone-eluting stents exhibited an improvement in the clinical and angiographic outcomes, as compared with the control stents. These results suggest that dexamethasone may play an important role in the inhibition of the polymer-induced inflammation in the era of drug-eluting stents.

C-Reactive Protein, Clinical Outcome, and Restenosis Rates After Implantation of Different Drug-Eluting Stents

Sirolimus-eluting stents (SESs), paclitaxel-eluting stents (PESs), and dexamethasone-eluting stents (DEXs) have anti-inflammatory properties; thus, the decreased in-segment restenosis rate observed with the use of these stents might be related to a weaker postprocedural inflammatory response. One hundred sixty consecutive patients with stable coronary artery disease who underwent successful single-vessel/lesion coronary artery stenting were prospectively studied. Thin-strut bare metal stents were deployed in 39 patients, SESs in 30, PESs in 61, and DEXs in 30. The 4 groups were similar with respect to demographic and angiographic variables and prevalence of risk factors. C-reactive protein (CRP) was measured at baseline and 24 and 48 hours after the procedure. Maximal increase in CRP was calculated as the increase in CRP at 48 hours/CRP compared with baseline. Angiographic follow-up was performed after 12.9 +/- 1.3 months or sooner, if needed, on the basis of clinical evidence. All patients presented a postprocedural increase in CRP that peaked at 48 hours (median 10.0 mg/L). Maximal CRP increase was similar across the 4 groups (medians 3.5 mg/L in the bare metal stent group, 3.6 mg/L in the SES group, 4.0 mg/L in the PES group, 3.5 mg/L in the DEX group, p = 0.45). Incidences of angiographic binary restenosis (>50% lumen diameter decrease) were 20.5% in the bare metal stent group, 3.3% in the SES group, 4.9% in the PES group, and 36.6% in the DEX group (p = 0.0004 for SES and PES groups vs bare metal stent and DEX groups). Postprocedural increase in CRP was significantly correlated with clinical and angiographic outcomes. In conclusion, the acute postprocedural systemic inflammatory response induced by drug-eluting stent implantation appears to be similar to that induced by bare metal stents. However, the restenosis rate is lower for SESs and PESs than for DEXs and bare metal stents. Thus, the decreased incidence of stent restenosis that was observed after SES and PES deployment is unlikely to be related to a decreased acute systemic inflammatory response, but rather to an increased local resistance to inflammatory mediators.

Dexamethasone-eluting stents and plasma concentrations of adhesion molecules in patients with unstable coronary syndromes: Results of the historically controlled SESAME study

Plasma concentrations of intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin may increase after percutaneous coronary intervention (PCI). The aim of this study was to assess whether anti-inflammatory treatment with steroid-eluting stents influenced concentrations of adhesion molecules after PCI in patients with unstable coronary syndromes. Consecutive patients with unstable coronary syndromes who were prospectively assigned to undergo implantation of a dexamethasone-eluting stent were compared with a control group of consecutive historical patients who received a similar non-drugeluting stent in the period immediately preceding availability of the steroid-eluting stents. Circulating concentrations of adhesion molecules were measured before the procedure and at 6 and 24 hours after implantation. The study included 50 patients who received the dexamethasone-eluting stent (41 men, 9 women; mean [SD] age, 60 [9] years) and 50 historical controls who received the non-drug-eluting stent (40 men, 10 women; mean age, 63 [11] years). Baseline values for the adhesion molecules were similar in the 2 groups: in patients who received the dexamethasone-eluting stent, mean (SD) values were 210 (41) ng/mL for ICAM-1, 637 (119) ng/mL for VCAM-1, and 46 (9) ng/mL for E-selectin; in the control group, the corresponding values were 218 (42), 618 (140), and 43 (10) ng/mL. Circulating concentrations at 24 hours were significantly lower in patients receiving the drug-eluting stent compared with controls for both ICAM-1 (279 [49] vs 338 [60] ng/mL, respectively; P = 0.001) and VCAM-1 (772 [163] vs 896 [207] ng/mL; P = 0.004). There was no significant between-group difference in E-selectin concentrations at 24 hours (60 [10] vs 56 [11] ng/mL). In this study, dexamethasone-eluting stents reduced plasma concentrations of ICAM-1 and VCAM-1 after PCI in patients with unstable coronary syndromes compared with historical controls.

Histopathologic alterations following local delivery of dexamethasone to inhibit restenosis in murine arteries

Dexamethasone-eluting stents are currently under evaluation to prevent post-angioplasty restenosis. The efficacy and safety of dexamethasone as an anti-restenotic agent is still unclear. We assess the effect of perivascular delivery of dexamethasone on vascular pathology in a mouse model of restenosis. In this study we investigate the ability of both systemic and local dexamethasone treatment to inhibit neointima formation after cuff placement around C57BL/6 mouse femoral artery. As in the clinical situation, systemic dexamethasone treatment shows adverse side effects in animals, including weight loss. In contrast, local delivery of dexamethasone using a drug-eluting polymer cuff inhibits neointima formation and has no systemic adverse effects. Pathobiological examination of the experimental arteries, however, reveals a dose-dependent medial atrophy, a reduction in vascular smooth muscle cells and collagen content, an increase in apoptotic cell count and disruption of the internal elastic lamina. Our results demonstrate that although local dexamethasone delivery is effective as an inhibitor for neointima formation, it is dose-dependently associated with adverse vascular morphological changes pointing to a loss of vascular integrity.

Effect of dexamethasone-eluting stents on systemic inflammatory response in patients with unstable angina pectoris or recent myocardial infarction undergoing percutaneous coronary intervention

The effect of treatment with steroid-eluting stents on systemic inflammatory response was investigated in patients with unstable angina pectoris or recent myocardial infarction who underwent percutaneous intervention. Compared with controls, dexamethasone-eluting stents significantly reduced C-reactive protein peak levels 48 hours after the procedure; this effect persisted for 7 days and was particularly evident in patients with elevated (>/=3 mg/L) preprocedural C-reactive protein values. Patients receiving a dexamethasone-eluting stent had lower adverse events during follow-up.

Intravascular ultrasonic comparative analysis of degree of intimal hyperplasia produced by four different stents in the coronary arteries

Intravascular ultrasound studies were performed at angiographic follow-up on 121 native coronary lesions treated with 1 bare metal stent (n = 50), high-dose dexamethasone-eluting stents (n = 18), non-polymer-based paclitaxel-eluting stents (n = 18), or sirolimus-eluting stents (n = 35). Paclitaxel- and sirolimus-eluting stents reduced mean intimal hyperplasia thickness compared with bare metal stents by 49% and 90% (p = 0.048 and p <0.001), respectively, whereas mean intimal hyperplasia thickness treated with dexamethasone-eluting stents was similar to those lesions treated with bare metal stents.