Pharmaceutical aspects of drug eluting stents.

This review focuses on the pharmaceutical aspects of the development of drug eluting stents. It discusses the different processes that can be used to obtain a controlled release of a drug from the stent as well as the coatings therefore applied. Results obtained for stents already available on the market or in a far stage of development are discussed.

Two-year clinical results of a polymer-free, paclitaxel-eluting stent: the ELUTES trial.

Aims: The ELUTES Study was a dose-finding trial to determine clinical safety and angiographic efficacy of a polymer-free, paclitaxel-eluting stent. The aim of this paper is to present the longer term follow-up.

Methods And Results: 192 patients with de novo lesions were randomised to either control or one of four doses of paclitaxel directly applied to a Cook Incorporated V-Flex Plus stent without polymer.

Stent-based tempamine delivery on neointimal formation in a porcine coronary model.

Background: Tempamine is one of new class of antioxidant agents, the nitroxides, which have shown a wide range of biological effects like suppressing free radical driven reactions to maintain cell functions. The objectives of this study were to evaluate the effect of a biodegradable polymer coated stent loaded with tempamine on in-stent neointimal formation.

Methods: Stainless steel stents were dip coated in biodegradable elastomeric poly (ester-amide) (co-PEA) or in polymer solution mixed with 50% (wt%) and 100% (wt%) tempamine.

Effects of cytochalasin D-eluting stents on intimal hyperplasia in a porcine coronary artery model.

Objective: To investigate whether cytochalasin D-eluting stents (CDES) suppress intimal hyperplasia in porcine coronary arteries and to compare the efficacy of paclitaxel and cytochalasin D as inhibitors of vascular smooth muscle cell (SMC) proliferation and platelet aggregation in vitro.

Methods: Rabbit platelet-rich plasma and SMC cultures derived from rabbit aortas were exposed to 10(-8)-10(-5) M cytochalasin D or paclitaxel. Stents directly coated with 2 microg cytochalasin D (low-dose CDES, n=12) and bare stents (n=12) were randomly deployed in the right and left coronary artery of 12 pigs.

Stent-mediated methylprednisolone delivery reduces macrophage contents and in-stent neointimal formation.

Objective: Corticosteroids have a wide range of biological effects. Stent-based methylprednisolone delivery could effectively suppress peri-strut inflammation and neointima induced by a polymer matrix. We tested the safety and efficacy of local stent-mediated methylprednisolone delivery using a biological coating on in-stent neointimal formation in a porcine coronary stent model.

Use of a tacrolimus-eluting stent to inhibit neointimal hyperplasia in a porcine coronary model.

In-stent restenosis remains an unresolved problem which occurs in 5-20% of patients undergoing coronary stenting within the first 3-6 months. Neointimal formation is the main contributor to in-stent restenosis. Stent-induced arterial injury and peri-strut inflammation are involved in the process of neointimal formation by activating cytokines and growth factors which induce smooth muscle cell dedifferentiation, migration, and proliferation.

Direct stenting versus direct stenting followed by centered beta-radiation with intravascular ultrasound-guided dosimetry and long-term anti-platelet treatment: results of a randomized trial: Beta-Radiation Investigation with Direct Stenting and Galileo in Europe (BRIDGE).

Objectives: We sought to assess the efficacy of vascular brachytherapy (VBT) combined with stenting for the primary prevention of restenosis.

Background: Intravascular brachytherapy after stent implantation for de novo lesions has been abandoned for the present. We revisited this procedure by optimizing all procedural steps-the use of glycoprotein IIb/IIa blockers, direct stenting, adequate radiation coverage, avoidance of edge damage, source centering, intravascular ultrasound-guided dosimetry, and continuation of a dual anti-platelet regimen for one year.

Dexamethasone-eluting stent: an anti-inflammatory approach to inhibit coronary restenosis.

The long-term efficacy of percutaneous coronary interventions is still hampered by restenosis. Restenosis is the result of a complex pathophysiological process, which is thought to be caused by an exaggerated healing response induced by the vascular injury caused by the percutaneous coronary interventions and the implantation of a foreign body (the stent). There is increasing evidence that inflammation plays an important role in the initiation and development of neointimal hyperplasia and subsequent restenosis.

Electrochemical polishing of 316L stainless steel slotted tube coronary stents.

Surface smoothness is one of the properties determining the performance of stents. Therefore, surface polishing shows its importance in the exploitation and production of stents. The present study explores electrochemical polishing of 316L stainless steel slotted tube coronary stents produced by laser cutting.

Evaluation of fluorinated polymers as coronary stent coating.

In this report, some fluorinated polyphosphazenes and polymethacrylates were selected for evaluation as coronary stent coating. After applying the polymer film by dipcoating, the stents were implanted in porcine coronary arteries. No acute thrombotic occlusions were observed.

Comparison of neointimal formation in polymer-free paclitaxel stents versus stainless stents (from the ASPECT and ELUTES randomized clinical trials).

The investigators examined 326 pairs of angiograms from 2 randomized dose-finding (0.2 to 3.1 microg paclitaxel/mm(2) of stent surface area) clinical trials of polymer-free paclitaxel-eluting stents in de novo lesions (the ASian Paclitaxel-Eluting stent Clinical Trial [ASPECT] and the European evaLUation of Taxol Eluting Stent [ELUTES]).

The sequential changes in myocardial thickness and thickening which occur during acute transmural infarction, infarct reperfusion and the resultant expression of reperfusion injury.

Aim: Successful primary PTCA (with TIMI 3 reflow) in patients with acute transmural infarction has been observed to result in an immediate abnormal increase in wall thickness associated with persisting abnormal post-systolic thickening. To understand the sequential changes in regional deformation during: (i) the development of acute transmural infarction, (ii) upon TIMI grade 3 infarct reperfusion and (iii) during the subsequent expression of reperfusion injury the following correlative experimental study was performed in a pure animal model in which there was no distal dispersion of thrombotic material causing either no reflow or secondary microvascular obstruction.

Methods: In 10 closed-chest pigs, a 90 min PTCA circumflex occlusion was used to induce a transmural infarction.

Cellular mechanisms of contractile dysfunction in hibernating myocardium.

Ischemic heart disease is a leading cause of chronic heart failure. Hibernation (ie, a chronic reduction of myocardial contractility distal to a severe coronary stenosis and reversible on revascularization) is an important contributing factor. The underlying cellular mechanisms remain however poorly understood.

Inhibition of restenosis with a paclitaxel-eluting, polymer-free coronary stent: the European evaLUation of pacliTaxel Eluting Stent (ELUTES) trial.

Background: The use of a stent to deliver a drug may reduce in-stent restenosis. Paclitaxel interrupts the smooth muscle cell cycle by stabilizing microtubules, thereby arresting mitosis.

Methods And Results: On the basis of prior animal studies, the European evaLUation of the pacliTaxel Eluting Stent (ELUTES) pilot clinical trial (n=190) investigated the safety and efficacy of V-Flex Plus coronary stents (Cook Inc) coated with escalating doses of paclitaxel (0.

Methotrexate loaded SAE coated coronary stents reduce neointimal hyperplasia in a porcine coronary model.

Objective: To evaluate the effect of stent based methotrexate delivery on neointimal hyperplasia.

Methods: Stainless steel coronary stents and biological polymer coated (SAE) stents were randomly implanted in coronary arteries of pigs with a stent to artery ratio of 1.1:1.

Addition of cytochalasin D to a biocompatible oil stent coating inhibits intimal hyperplasia in a porcine coronary model.

Background: Polymer-based, drug-eluting stents, are currently under extensive investigation in the conquest against in-stent restenosis. Concern remains, however, about potential long-term lack of biocompatibility of the polymers used in these studies. Therefore, this study aimed to evaluate in porcine coronary arteries (1) the in vivo biocompatibility of a new natural, eicosapentaenoic acid oil stent-coating and (2) the efficacy of this coating in preventing in-stent restenosis when cytochalasin D--an inhibitor of actin filament formation, that interferes with cell proliferation and migration--was added.

Randomized study to compare balloon angioplasty and elective stent implantation in venous bypass grafts: the Venestent study.

The aim of the study was to compare acute and long-term angiographic and clinical outcome of balloon angioplasty and elective stenting in de novo lesions in the body of a saphenous vein graft (SVG). A total of 150 patients, with de novo lesions in SVG, were randomly assigned to balloon angioplasty or elective Wiktor I stent implantation. The angiographic restenosis rate at 6-month follow-up was 32.

The effect of reduced blood-flow on the coronary wall temperature. Are significant lesions suitable for intravascular thermography?

Aims: The purpose of this study was to investigate the relation between acute coronary flow reduction and arterial wall temperature.

Methods And Results: Five pigs with normal coronary arteries were catheterized. Arterial wall temperature was studied with a thermographic system that uses a 4-thermistor sensor tip.

Study of antirestenosis with the BiodivYsio dexamethasone-eluting stent (STRIDE): a first-in-human multicenter pilot trial.

The aim of this multicenter pilot study was to evaluate the acute safety and efficacy of the dexamethasone-eluting stent (0.5 microg/mm(2) of stent) implanted in patients with de novo single-vessel disease. This study included 71 patients, 42% of whom had unstable angina pectoris.

Local methylprednisolone delivery using a BiodivYsio phosphorylcholine-coated drug-delivery stent reduces inflammation and neointimal hyperplasia in a porcine coronary stent model.

Phosphorylcholine (PC)-coated stents have shown excellent blood and tissue biocompatibility in porcine coronary arteries. The purpose of this study was to determine the efficacy of local methylprednisolone (MP) delivery using PC-coated stents to inhibit inflammatory response and in-stent neointimal hyperplasia in an overstretched porcine coronary model. BiodivYsio (Biocompatibles, Farnham, Surrey, UK) PC-coated drug delivery (DD) stents and DD stents loaded with a high dose of MP (269 microg) were implanted in the coronary arteries of 20 pigs with a balloon/artery ratio of 1.

Long-term biocompatibility evaluation of a novel polymer-coated stent in a porcine coronary stent model.

Background: Polymer coatings have been used to modify the surface of stents and to serve as a matrix for local drug delivery.

Methods: Bare stainless steel stents or poly-bis-trifluorethoxy phosphazene (PTFEP) dip-coated stents (Coroflex, Germany) were randomly implanted into porcine coronary arteries with a balloon-to-artery ratio of 1.1-1.

Long term effects of nisoldipine on the progression of coronary atherosclerosis and the occurrence of clinical events: the NICOLE study.

Background: Earlier angiographic studies have suggested that calcium antagonists may prevent the formation of new coronary lesions and the progression of minimal lesions. Conversely, a meta-analysis suggested that these drugs may increase cardiovascular mortality and morbidity in patients with coronary heart disease.

Objective: To investigate whether nisoldipine retards the progression of coronary atherosclerosis or reduces the occurrence of clinical events.

Arterial wall temperature following coronary stent implantation in pigs: the role of post-stent inflammation.

Background: The purpose of this study was to investigate in vivo the arterial wall temperature after coronary stent implantation in pigs.

Methods: We performed cardiac catheterization in 20 pigs with normal coronary arteries. Arterial wall temperature was studied with a thermography system that uses a 4-thermistor sensor tip.