scholarly journals Factors Influencing 1st and 2nd Generation Drug-Eluting Stent Performance: Understanding the Basic Pharmaceutical Drug-in-Polymer Formulation Factors Contributing to Stent Thrombosis Do We Really Need to Eliminate the Polymer?

2021 ◽  
Vol 24 ◽  
pp. 435-461
Author(s):  
Iva Srdanovic
Keyword(s):  
Stent Thrombosis ◽  
Biodegradable Polymers ◽  
Biodegradable Polymer ◽  
Metal Stents ◽  
Burst Release ◽  
Late Stent Thrombosis ◽  
Very Late Stent Thrombosis ◽  
2Nd Generation ◽  
Durable Polymer ◽  
Drug Eluting

Drug-eluting stents (DES) have a major role in treating cardiovascular disease. The evolution of bare metal stents into 1st generation durable-polymer DES (DP-DES) reduced the rate of in-stent restenosis (ISR) and the need for repeat-revascularization. However, clinical outcomes showed similar rates of late stent thrombosis (ST<1 year) and higher rates of very late stent thrombosis (ST>1 year) necessitating the advent of 2nd generation more biocompatible polymer DES and biodegradable-polymer DES (BP-DES) that reduced ST rates with shorter dual anti-platelet therapy (DAPT). Despite the improvements in drugs and polymer biocompatibility for both durable and biodegradable polymers, stent thrombosis remains an issue. Doubts remain about the safety and efficacy of the more biocompatible 2nd generation durable polymers in respect to vessel inflammatory and thrombogenic response as compared to biodegradable polymers despite clinical trial and meta-analyses evidence indicating that 2nd generation DP-DES are non-inferior to BP-DES for stent thrombosis. A long-term presence of the polymer can cause inflammation and thrombogenesis. However, the cause of stent thrombosis is multi-factorial from a drug-in-polymer formulation perspective; e.g., drug release kinetics, drug physiochemical and pharmacological properties, degradation kinetics; polymer biocompatibility and hemocompatibility and coating properties. It appears that the focus should be on controlling burst release and developing more biocompatible, durable polymers, especially considering the cost of PCI utilizing biodegradable, polymer-free and bioresorbable scaffolds. This may give an insight into certain DP-DES effectiveness as compared to BP-DES for the existing clinical data and improve future stent development.

Stent Thrombosis with Biodegradable Polymer Drug-Eluting Stents versus Durable Polymer Sirolimus-Eluting Stents: An Update Meta-Analysis

Cardiology ◽  
2015 ◽  
Vol 130 (2) ◽  
pp. 96-105 ◽  
Author(s):  
Lin Zhu ◽  
Yi Ning Lv ◽  
Li Yu Wang
Keyword(s):  
Stent Thrombosis ◽  
Biodegradable Polymer ◽  
Meta Analysis ◽  
Drug Eluting Stents ◽  
Late Stent Thrombosis ◽  
Cardiac Events ◽  
Comparable Rate ◽  
Very Late Stent Thrombosis ◽  
Durable Polymer ◽  
Drug Eluting

Objective: Durable polymer sirolimus-eluting stents (DP-SES) are associated with a low risk of stent thrombosis; biodegradable polymer drug-eluting stents (BP-DES) were designed to reduce these risks. However, their benefits are still variable. Method: We undertook a meta-analysis of randomized trials identified by systematic searches of Medline, Embase, and the Cochrane Database. Results: Eleven studies (9,676 patients) with a mean follow-up of 22.6 months were included. Overall, compared with DP-SES, BP-DES significantly lowered the rate of definite or probable stent thrombosis (RR, 0.73; 95% CI, 0.55-0.97; p = 0.03; I2 = 0.0%) due to a decreased risk of very late stent thrombosis (RR, 0.26; 95% CI, 0.11-0.63; p = 0.00; I2 = 0.0%). However, BP-DES were associated with a comparable rate of early and late stent thrombosis. Meanwhile, BP-DES were associated with a broadly equivalent risk of target vessel revascularization (RR, 0.90; 95% CI, 0.78-1.03; p = 0.13; I2 = 0.0%), cardiac death (RR, 0.89; 95% CI, 0.72-1.09; p = 0.24; I2 = 0.0%), myocardial infarction (RR, 1.03; 95% CI, 0.84-1.26; p = 0.79; I2 = 0.0%), and major adverse cardiac events (MACE; RR, 0.91; 95% CI, 0.83-1.0; p = 0.08; I2 = 0.0%). Furthermore, angiographic data showed that in-stent and in-segment late luminal loss were similar between the two groups. Conclusions: Compared with DP-SES, BP-DES were associated with a lower rate of very late stent thrombosis and an equivalent risk of MACE. Larger randomized studies are needed to confirm this finding.

Abstract 2564: No Late and no Very Late Stent Thrombosis with a Drug-Eluting Stent of the Second Generation: 2 Years Results from the Randomized NOBORI-I Trial

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Sigmund Silber ◽  
Bernard Chevallier ◽  
Patricl Serruys ◽  
E. Garcia ◽  
Gregorio Maranon ◽  
...  
Keyword(s):  
Stent Thrombosis ◽  
Biodegradable Polymer ◽  
Vessel Wall ◽  
First Generation ◽  
Second Generation ◽  
Late Stent Thrombosis ◽  
Very Late Stent Thrombosis ◽  
Drug Elution ◽  
Durable Polymer ◽  
Drug Eluting

Background: Late (after 30 days to 1 year) and very late (after 1 year) stent thrombosis is a continuous concern for drug-eluting stents (DES) of the first generation. These stents are characterized by their durable polymer and a ,,360 degree“ elution of the antiproliferative drug not only into the vessel wall, but also into the blood stream. Therefore, the second generation Nobori stent was developed with a biodegradable polymer and a drug elution restricted only to the vessel wall (abluminal coating). The drug, Biolimus A9, is a potent antiproliferative and antiinflammatory Limus derivative. Methods: The NOBORI-I trial was a prospective randomized study designed to compare the Nobori stent with the Taxus stent (2:1) in pats with single de-novo native coronary lesions, a vessel diameter of 2.5–3.5 mm and a lesion length below 25 mm. Predilatation was required. The primary endpoint was in-stent late lumen loss (LL) at 9 months. The study was designed as a noninferiority trial. 363 pats were enrolled in 29 sites in Europe, Asia and Australia. Clopidogrel (in addition to ASA) was recommended for at least 6 months. Results: With an in-stent LL of 0.12 mm in the Nobori and 0.33 mm in the Taxus group (p <0.001) the primary endpoint was reached, with a significant result also for superiority. The results for late and very late stent thrombosis are depicted in the table . Dual antiplatelet therapy was present at one year in 52% of the pats in the Nobori and in 55% of the pats in the Taxus group. After 2 years, it was maintained in 25% of the Nobori and in 20% of the Taxus pats. Conclusions: As compared to a DES of the first generation with a durable polymer and circumferential drug release, the second generation Nobori stent with its biodegradable polymer and a drug-elution restricted to the vessel wall seems to be safer. Due to the limited power of this study regarding safety, higher number of patients are needed to corrobarate these promising findings.

scholarly journals Very Late Stent Thrombosis 42 Months after Implantation of Sirolimus-Eluting Stent and Discontinuation of Antiplatelet Therapy

2009 ◽  
Vol 2009 ◽  
pp. 1-2 ◽  
Author(s):  
Dirk Sibbing ◽  
Karl-Ludwig Laugwitz ◽  
Lorenz Bott-Flügel ◽  
Jürgen Pache
Keyword(s):  
Stent Thrombosis ◽  
Safety Concern ◽  
Bare Metal Stents ◽  
Drug Eluting Stent ◽  
Metal Stents ◽  
Late Stent Thrombosis ◽  
Stent Deployment ◽  
Very Late Stent Thrombosis ◽  
Drug Eluting ◽  
Sirolimus Eluting Stent

Although safety profiles of sirolimus-eluting stents do not seem to differ in short-to-medium term from those of bare-metal stents, late stent thrombosis after deployment of drug-eluting stents has emerged as a potential safety concern in the era of high-pressure stent implantation. Here, we describe the case of a patient with acute myocardial infarction due to stent thrombosis of a sirolimus-eluting stent 42 months after stent deployment and 5 weeks after discontinuation of aspirin treatment. To the best of our knowledge, this is one of the most delayed cases of sirolimus-eluting stent thrombosis described so far. The case emphasizes the potential risk that late stent thrombosis can unpredictably occur at any time point after drug-eluting stent deployment.

Sign in / Sign up

Export Citation Format

Share Document