Dynamics of Arterial Wall Transport for Small Hydrophobic Drugs

2012 ◽  
Author(s):  
Franz Bozsak ◽  
Jean-Marc Chomaz ◽  
Abdul I. Barakat
Keyword(s):  
Smooth Muscle ◽  
Stent Implantation ◽  
Side Effect ◽  
Arterial Wall ◽  
Drug Eluting Stents ◽  
Adverse Side Effect ◽  
Late Stent Thrombosis ◽  
Increased Risk ◽  
Drug Eluting ◽  
Small Hydrophobic

Drugs used in drug-eluting stents (DES) to inhibit proliferation of smooth muscle cells (SMCs) also limit re-endothelialization at the site of stent implantation [1]. Thus, treated patients face an increased risk of late-stent thrombosis. Avoiding this adverse side effect represents one of the major challenges in the design of next-generation DES.

scholarly journals Coronary Aneurysm Occurring Late after Drug-Eluting Stent Implantation

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Etan Abergel ◽  
Ariel Roguin
Keyword(s):  
Case Report ◽  
Stent Thrombosis ◽  
Stent Implantation ◽  
Healing Process ◽  
Late Stent Thrombosis ◽  
Very Late Stent Thrombosis ◽  
Coronary Stent Implantation ◽  
Increased Risk ◽  
Drug Eluting

Drug-eluting stents may affect the normal healing process of the vessel wall and the remodeling process and may lead to late stent malapposition (LSM). The known incidence of this phenomen originates from short-term angiographic follow-up studies. We describe a case report of very late stent malapposition and marked positive vessel remodeling 3 years after sirolimus-eluting coronary stent implantation. Angiography performed one year after stent implantation was normal. Thus, the abnormalities developed sometime between years 1 and 3. The cause is unknown, but it is reasonable to suggest a local effect of the medication/polymer of the stent. LSM rate and aneurysmal formation is higher in DES than in BMS and may be associated with increased risk for late stent thrombosis. Currently, the risk of very late stent thrombosis after DES implantation is of major concern. As observed in this case report, LSM might occur and develop very late. This has significant consequences especially to the many asymptomatic patients with DES implanted many years ago and the recommendation of dual antiplatelet therapy. More studies with late and very late follow up are needed to better define this finding, its mechanism, how to avoid it, and how to treat it properly.

The CXCR4 antagonist POL5551 is equally effective as sirolimus in reducing neointima formation without impairing re-endothelialisation

2012 ◽  
Vol 107 (02) ◽  
pp. 356-368 ◽  
Author(s):  
Karim Hamesch ◽  
Pallavi Subramanian ◽  
Xiaofeng Li ◽  
Klaus Dembowsky ◽  
Eric Chevalier ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Neointimal Hyperplasia ◽  
High Dose ◽  
Neointima Formation ◽  
Late Stent Thrombosis ◽  
Cxcr4 Antagonist ◽  
Increased Risk ◽  
Drug Eluting ◽  
Stent Coating ◽  
Deficient Mice

SummaryImpaired endothelial recovery after the implantation of drug-eluting stents is a major concern because of the increased risk for late stent thrombosis. The disruption of the chemokine axis CXCL12/CXCR4 inhibits neointima formation by blocking the recruitment of smooth muscle progenitor cells. To directly compare a CXCR4-targeting treatment strategy with drugs that are currently used for stent coating, we studied the effects of the CXCR4 antagonist POL5551 and the drug sirolimus on neointima formation. Apolipoprotein E-deficient mice were treated with POL5551 or sirolimus continuously for 28 days after a carotid wire injury. POL5551 inhibited neointima formation by 63% (for a dosage of 2 mg/kg/day) and by 70% (for a dosage of 20 mg/kg/day). In comparison, sirolimus reduced the neointimal area by 69%. In contrast to treatment with POL5551 during the first three days after injury, injection of POL5551 (20 mg/kg) once per day for 28 days diminished neointimal hyperplasia by 53%. An analysis of the cellular composition of the neointima showed a reduction in the relative smooth muscle cell (SMC) and macrophage content in mice that had been treated with a high dose of POL5551. In contrast, the diminished SMC content after sirolimus treatment was associated with a neointimal enrichment of macrophages. Furthermore, endothelial recovery was impaired by sirolimus, but not by POL5551. Therefore, the inhibition of CXCR4 by POL5551 is equally effective in preventing neointima formation as sirolimus, but POL5551 might be more beneficial because treatment with it results in a more stable lesion phenotype and because it does not impair re-endothelialisation.

ANISOTROPIC TRANSPORT THROUGH POLYMER LAYER AND POROUS ARTERIAL WALL WITH BINDING IN DRUG-ELUTING STENTS USING THE FEM

2018 ◽  
Author(s):  
fabiane aparecida dos santos frazzoli ◽  
Rachel Manhaes de Lucena ◽  
Norberto Mangiavacchi ◽  
José da Rocha Miranda Pontes ◽  
Gustavo Rabello dos Anjos ◽  
...  
Keyword(s):  
Arterial Wall ◽  
Polymer Layer ◽  
Drug Eluting Stents ◽  
Drug Eluting ◽  
Anisotropic Transport

Abstract 40: Hospital Variation in Premature Clopidogrel Discontinuation following Drug Eluting Stent Placement and Adverse Cardiovascular Outcomes from the VA Clinical Assessment, Reporting, and Tracking System for Cath Labs (CART-CL)

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Rebecca Vigen ◽  
Thomas M Maddox ◽  
Colin O'Donnell ◽  
Deepak L Bhatt ◽  
Thomas T Tsai ◽  
...  
Keyword(s):  
Tracking System ◽  
Adverse Outcomes ◽  
Drug Eluting Stents ◽  
Drug Eluting Stent ◽  
Hospital Level ◽  
Pharmacy Refill ◽  
Hospital Variation ◽  
Increased Risk ◽  
Drug Eluting ◽  
Clopidogrel Therapy

Background: Clopidogrel is recommended for 1 year following drug eluting stent (DES) placement and premature discontinuation has been associated with adverse outcomes. The extent of variation in premature discontinuation across hospitals within an integrated healthcare system is unknown. Accordingly, we assessed variation in premature clopidogrel discontinuation across all VA PCI sites and whether there was an association between hospitals with higher rates of premature discontinuation and adverse outcomes. Methods: We used the VA CART-CL registry which includes all PCIs with drug eluting stents performed between 10/01/08 and 09/30/09 at 55 VA cath labs that used CART. We evaluated the frequency of patients who prematurely discontinue clopidogrel at 6 and 9 months using pharmacy refill data. Multivariable regression assessed the association between premature discontinuation and all-cause mortality and/or myocardial infarction (MI). We then grouped sites into quartiles of premature discontinuation and evaluated the association between hospital level premature discontinuation and adverse outcomes. Results: Of the 7,022 patients who received a DES, 6.3% discontinued by 6 months, and 10.2% by 9 months. After risk adjustment, patients who discontinued clopidogrel prematurely had increased risk of adverse events with HR of 5.42 at 6 months (95% CI 4.22 – 6.99), and 6.24 at 9 months (95% CI 4.98 – 7.83). There was a significant trend in the unadjusted rates within quartiles toward increased risk of adverse outcomes among hospitals with greater rates of patients who discontinue prematurely by 6 months (p < 0.01 for trend, OR 1.65 CI 1.07 – 2.62 for comparison between quartile 1 and 4). Conclusion: Premature discontinuation of clopidogrel is associated with adverse outcomes among patients who receive drug eluting stents. Hospitals with higher rates of premature discontinuation of clopidogrel have higher rates of adverse outcomes. Hospital-level interventions to reduce early discontinuation of clopidogrel therapy have the potential to improve outcomes of patients who receive a DES.

Numerical Simulation of Transport Through Polymer Layer and Porous Arterial Wall of Sirolimus and Paclitaxel in Drug-eluting Stents

2021 ◽  
Author(s):  
Haroldo Rosman Junior ◽  
Rachel Manhaes de Lucena ◽  
Norberto Mangiavacchi ◽  
José da Rocha Miranda Pontes ◽  
Sean McGinty
Keyword(s):  
Numerical Simulation ◽  
Arterial Wall ◽  
Polymer Layer ◽  
Drug Eluting Stents ◽  
Drug Eluting

scholarly journals 10-Year Paclitaxel Dose-Related Outcomes of Drug-Eluting Stents Treated Below the Knee in Patients with Chronic Limb-Threatening Ischemia (The PADI Trial)

2020 ◽  
Vol 43 (12) ◽  
pp. 1881-1888 ◽  
Author(s):  
Louise C. D. Konijn ◽  
Thijs Wakkie ◽  
Marlon I. Spreen ◽  
Pim A. de Jong ◽  
Lukas C. van Dijk ◽  
...  
Keyword(s):  
Bare Metal Stents ◽  
Drug Eluting Stents ◽  
Metal Stents ◽  
Survival Analyses ◽  
Below The Knee ◽  
Increased Risk ◽  
Significant Difference ◽  
Drug Eluting ◽  
Related Mortality

Abstract Purpose Recently, two meta-analyses concluded that there appears to be an increased risk of long-term mortality of paclitaxel-coated balloons and stents in the superficial femoral and popliteal artery, and paclitaxel-coated balloons below the knee. In this post hoc study of the PADI Trial, we investigated the long-term safety of first-generation paclitaxel-coated drug-eluting stents (DES) below the knee and the dose–mortality relationships of paclitaxel in patients with chronic limb-threatening ischemia (CLI). Materials and Methods The PADI Trial compared paclitaxel-coated DES with percutaneous transluminal angioplasty with bail-out bare-metal stents (PTA ± BMS) in patients with CLI treated below the knee. Follow-up was extended to 10 years after the first inclusion, and survival analyses were performed. In addition, dose-related mortality and dose per patient weight-related mortality relations were examined. Results A total of 140 limbs in 137 patients were included in the PADI Trial. Ten years after the first inclusion, 109/137 (79.6%) patients had died. There was no significant difference between mortality in the DES group compared with the PTA ± BMS group (Log-rank p value = 0.12). No specific dose-related mortality (HR 1.00, 95% CI 0.99–1.00, p = 0.99) or dose per weight mortality (HR 1.05, 95% CI 0.93–1.18, p = 0.46) relationships were identified in the Cox-proportional Hazard models or by Kaplan–Meier survival analyses. Conclusions There is a poor 10-year survival in both paclitaxel-coated DES and PTA ± BMS in patients with CLI treated below the knee. No dose-related adverse effects of paclitaxel-coated DES were observed in our study of patients with CLI treated below the knee. Level of Evidence The PADI Trial: level 1, randomized clinical trial

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