In vivo evaluation of a biolimus eluting nickel titanium self expanding stent with overlapping balloon expandable drug eluting and bare metal stents in a porcine coronary model.

AIMS: Long lesions and complex vessel anatomy frequently require the use of overlapping stents to treat a lesion. The purpose of this study was to evaluate the long-term effects of overlapping the Axxess Biolimus A9 eluting stent (BES) with two of the most commonly used, commercially available drug eluting stents. These stents were compared to BxVelocity bare metal (BMS) stents in a porcine coronary stent-injury model. METHODS AND RESULTS: Nineteen juvenile farm swine, 25-35 kg in weight, 3-6 months in age were utilised. Each animal received an Axxess stent to their coronary artery as permitted by the individual animal's anatomy. A second stent, either a Cypher, sirolimus eluting stent (SES) or, a Taxus, paclitaxel eluting stent (PES), or a BxVelocity bare metal stent (BMS) were implanted in an overlapped fashion. The animals were then followed for either 28 or 180 days as specified by a randomisation scheme. At the end of each follow-up period, they were euthenised, and the vessels containing the overlapping stents were harvested, processed into histological sections, and analysed. Compared to bare metal stents, overlapped segments using DES exhibited delayed vascular healing compared to both the proximal and distal non-overlap sites at each of the follow-up time point. Overall, in the non-overlap stent segments, SES induced significantly more inflammation and neointimal hyperplasia compared to PES and BMS. CONCLUSIONS: In this study of BMS and two different types of DES overlapped with the Axxess Biolimus A9 eluting stent, we found that while there was a delay in the degree of vascular healing with DES compared to BMS, the specific type of DES that was overlapped with BES did not affect the behaviour of the overlap zone in terms of most of the histomorphometric measures at 28 or 180 days. This was true whether the stent was drug eluting or bare metal. More inflammation with delayed healing was seen in the SES compared to PES and BMS.

9-month clinical, angiographic, and intravascular ultrasound results of a prospective evaluation of the Axxess self-expanding biolimus A9-eluting stent in coronary bifurcation lesions: the DIVERGE (Drug-Eluting Stent Intervention for Treating Side Branches Effectively) study.

OBJECTIVES: This study sought to assess the safety and performance of the Axxess (Devax Inc., Lake Forest, California) self-expanding drug-eluting stent in coronary bifurcation lesions. BACKGROUND: Percutaneous treatment of coronary bifurcations is a predictor of adverse late outcomes, in part because of the lack of dedicated devices. METHODS: Patients with de novo bifurcation lesions were prospectively enrolled in a multicenter study. The Axxess stent was deployed at the level of the carina followed by additional sirolimus-eluting stents in the distal parent vessel (PV) and/or side branch (SB). All patients underwent clinical follow-up at 9 months; 150 were to receive control angiography and 76 were to receive intravascular ultrasound. The primary end point was the rate of major adverse cardiac events (MACE): a composite of death, myocardial infarction (MI), and target lesion revascularization (TLR). Secondary end points included in-segment restenosis, late loss, and percent neointimal volume obstruction. RESULTS: Overall, 302 patients were treated with 299 Axxess stents (99%). Additional stenting of 1 branch was performed in 21.7% of patients (17.7% PV, 4% SB), and of both branches in 64.7%. At 9 months, 99.3% of patients returned for clinical follow-up; from the angiographic and IVUS substudies, 93.3% and 89.4% returned. The cumulative 9-month MACE rate was 7.7% (0.7% death, 3.3% non-Q-wave MI, 1.0% Q-wave MI, 4.3% TLR). Subacute and late stent thrombosis occurred in 0.7% and 0.3% of patients. Total restenosis was 6.4% (3.6% PV, 4.3% SB), late loss was 0.20 +/- 0.41 mm in the PV and 0.17 +/- 0.34 mm in the SB. In the Axxess stent segment, percent neointimal volume obstruction was 4.3 +/- 5.2%. CONCLUSIONS: This prospective multicenter study confirms the safety and performance of the Axxess stent in bifurcation lesions. (Drug-Eluting Stent Intervention for Treating Side Branches Effectively; ACTRN12606000259549).

Six-month clinical and angiographic results of a dedicated drug-eluting stent for the treatment of coronary bifurcation narrowings.

Percutaneous intervention for coronary bifurcation lesions has been associated with increased clinical complication rates compared with nonbifurcation lesions, primarily as a result of restenosis. Therefore, there is a need for new techniques. The purpose of this study was to evaluate a new drug-eluting stent and implantation technique for the treatment of de novo coronary bifurcation lesions. The Axxess Plus trial was a prospective multicenter single-arm study that enrolled 139 patients. Each patient received a self-expanding, conically shaped nickel-titanium Axxess Plus biolimus A9-eluting stent at the level of the carina. Depending on the lesion anatomy, additional nonstudy stents were placed distally if necessary. Clinical and angiographic follow-up were scheduled at 6 months after the procedure. The overall rate of target lesion revascularization was 7.5% at 6 months. A mean of 2.4 stents were implanted per patient; 51.2% of patients received a stent to the side branch, 29.4% received balloon angioplasty only, and 20.6% of side branches were not treated. In-stent late loss in the Axxess stents was 0.09 mm. Incidences of angiographic in-stent restenosis were 7.1% in the parent vessel stents and 9.2% in the group receiving stents in the side branch (7.9% excluding bare metal stents placed distal to the Axxess stent), compared with 25% for balloon angioplasty treatment and 12% for no treatment. Late stent thrombosis was observed in 3 cases, 2 of which were associated with confirmed premature cessation of antiplatelet therapy. In conclusion, the Axxess Plus conical stent effectively treats bifurcation lesions alone or in conjunction with other drug-eluting stents.

Long-term effects of novel biolimus eluting DEVAX AXXESS plus nitinol self-expanding stent in a porcine coronary model.

OBJECTIVE: The purpose of this study was to evaluate the long-term effects of the DEVAX AXXESS biolimus eluting stent (BES) in a porcine coronary model, compared with those of bare metal stent (BMS) and polymer only stent (POS) controls. BACKGROUND: Excessive neointimal growth has been identified as a major cause of late failure of percutaneous coronary interventions. The effect of drug eluting from self-expanding stents for prevention of neointimal hyperplasia has not been studied before. The DEVAX AXXESS is a self-expanding nickel titanium stent, coated with antiproliferative compound-biolimus. METHODS: Twenty juvenile farm swine, 25-35 kg in weight, 3-6 months in age were used. Each animal received a stent to the left anterior descending artery, left circumflex or right coronary arteries as permitted per anatomy. The chronic vascular response after BES implantation was compared with that after BMS and POS implantation at 28, 90, and 180 days follow-up. RESULTS: The 28-day outcome by quantitative coronary angiography (QCA) showed significant increase in minimal luminal diameter (MLD) in the BES (MLD: 2.90 +/- 0.97, 2.39 +/- 0.90, 1.59 +/- 0.91; P = 0.009) compared with BMS and POS, respectively. By histomorphometric analysis, there was also a corresponding significant reduction in neointimal tissue proliferation in the BES (average neointimal area: 2.78 +/- 0.07, 5.46 +/- 0.66, 8.42 +/- 0.85; P = 0.002) compared with that in BMS and POS controls, respectively at 28-days follow-up. At 90 and 180 days, the mean neointimal area was not significantly different between the BES and the controls. CONCLUSIONS: BES favorably modulates the neointimal tissue formation for 28 days, in the porcine coronary model. Long-term inhibition of neointimal hyperplasia is not sustained most likely because of the delayed cellular proliferation and inflammation in the vessel wall.

The effect of variable release kinetics on Paclitaxel efficacy from a drug eluting stent in a porcine model.

AIMS: Paclitaxel is a potent and effective inhibitor of neointimal proliferation after coronary stenting. The Conor stent loaded with Paclitaxel can be programmed with multi-parameter matrix of dose, temporal release profiles and release pathways. The aim of this study was to determine the most efficacious dose and release pattern of Paclitaxel in a porcine model and parallels the PISCES trial. METHODS: 32 farm pigs were implanted with Conor stents loaded with 10 or 30 microg of Paclitaxel with, 10 or 30 day and mural or bidirectional release patterns. Angiographic and histomorphometric analysis was -performed at 30 and 90 days. RESULTS: All doses of Paclitaxel were angiographically superior to control (P < 0.01). At 30 days, intimal thickness was similar between Pisces D4 (30 microg/10 days, bidirectional release), D5 (10 microg/30 day mural) and D6 (30 microg/30 day, mural) with D4 having the lowest intimal thickness (167+/-59 microm). There was a significant increase in the mural injury associated with D4 in comparison to all other doses (P < 0.00001). At 90 days D4 was significantly worse in comparison to Pisces D5 and D6; (P < 0.01) and Pisces D5 and D6 were similar to controls. CONCLUSIONS: 10 day release of Paclitaxel may be too short a period to inhibit neointimal proliferation after coronary stenting, or the rapid release of Paclitaxel may induce chemical injury causing secondary insult to the artery resulting in a rebound increase in intimal thickness at 90 days. These data parallel clinical findings in the PISCES trial.

Balloon-based radiation therapy for treatment of in-stent restenosis in human coronary arteries: results from the BRITE I study.

Catheter-based intracoronary radiation therapy demonstrated reduction of the recurrence rate of in-stent restenosis by 35%-50% when compared to conventional therapy. The objectives of this study were to determine the safety and feasibility of a new balloon-shaped source design and a higher applied dose to reduce the restenosis rates. Thirty-two patients with in-stent restenosis who met study eligibility criteria were successfully treated with standard PCI techniques. Following a successful intervention, a P-32 beta-balloon source was positioned to cover the angioplasty site and a dose of a 20 Gy at 1 mm from the surface of the source was administered. The primary endpoint was a composite of major adverse cardiac events (any death, MI, emergent CABG, or repeat target vessel revascularization) during 6 months of follow-up. At 6 months, only one patient underwent repeat PTCA to the target vessel (3%). There were no instances of death, emergency surgery, late thrombosis, total occlusions, or MI. Binary restenosis measured by QCA at the stented segment was 0% and for the whole analysis vessel was 7.5%. Beta-radiation delivered with a balloon P-32 source design for patients with in-stent restenosis results in lower than expected rate of angiographic and clinical restenosis and the absence of late complications.