Biodegradable-polymer drug-eluting stents vs. bare metal stents vs. durable-polymer drug-eluting stents: a systematic review and Bayesian approach network meta-analysis

Kang, Si-Hyuck,Park, Kyung Woo,Kang, Do-Yoon,Lim, Woo-Hyun,Park, Kyung Taek,Han, Jung-Kyu,Kang, Hyun-Jae,Koo, Bon-Kwon,Oh, Byung-Hee,Park, Young-Bae,Kandzari, David E.,Cohen, David J.,Hwang, Seung-Sik The European Society of Cardiology 2014 European heart journal Vol.35 No.17

<P><B>Background</B></P><P>The aim of this study was to compare the safety and efficacy of biodegradable-polymer (BP) drug-eluting stents (DES), bare metal stents (BMS), and durable-polymer DES in patients undergoing coronary revascularization, we performed a systematic review and network meta-analysis using a Bayesian framework.</P><P><B>Methods and results</B></P><P>Study stents included BMS, paclitaxel-eluting (PES), sirolimus-eluting (SES), endeavor zotarolimus-eluting (ZES-E), cobalt–chromium everolimus-eluting (CoCr-EES), platinium–chromium everolimus-eluting (PtCr-EES), resolute zotarolimus-eluting (ZES-R), and BP biolimus-eluting stents (BP-BES). After a systematic electronic search, 113 trials with 90 584 patients were selected. The principal endpoint was definite or probable stent thrombosis (ST) defined according to the Academic Research Consortium within 1 year.</P><P><B>Results</B></P><P>Biodegradable polymer-biolimus-eluting stents [OR, 0.56; 95% credible interval (CrI), 0.33–0.90], SES (OR, 0.53; 95% CrI, 0.38–0.73), CoCr-EES (OR, 0.34; 95% CrI, 0.23–0.52), and PtCr-EES (OR, 0.31; 95% CrI, 0.10–0.90) were all superior to BMS in terms of definite or probable ST within 1 year. Cobalt–chromium everolimus-eluting stents demonstrated the lowest risk of ST of all stents at all times after stent implantation. Biodegradable polymer-biolimus-eluting stents was associated with a higher risk of definite or probable ST than CoCr-EES (OR, 1.72; 95% CrI, 1.04–2.98). All DES reduced the need for repeat revascularization, and all but PES reduced the risk of myocardial infarction compared with BMS.</P><P><B>Conclusions</B></P><P>All DESs but PES and ZES-E were superior to BMS in terms of ST within 1 year. Cobalt–chromium everolimus-eluting stents was safer than any DES even including BP-BES. Our results suggest that not only the biodegradability of polymer, but the optimal combination of stent alloy, design, strut thickness, polymer, and drug all combined determine the safety of DES.</P>

약물 방출 스텐트의 약물 방출 및 기계적 특성에 Ethylene Vinyl Alcohol와 Cellulose Acetate Butyrate가 미치는 영향

장부남 ( Bunam Jang ),강성남 ( Sung Nam Kang ),금창헌 ( Chang Hun Kum ) 한국키틴키토산학회 2017 한국키틴키토산학회지 Vol.22 No.1

Although drug-eluting stents have reduced the problem of restenosis, such stents exhibit side effects such as inhibition of re-endothelialization and inflammatory reactions due to persistent drug reactions and sensitivity of polymers. To solve this problem, suppressing the continuous drug reaction by controlling drug release behavior induce rapid vascular re-endothelization. In this study, we attempted to control drug release from a paclitaxel- and cilostazol-containing stent using ethylene vinyl alcohol (EVOH). We then used a scanning electron microscope and atomic force microscope to observe changes on the surface of the drug-releasing stent following the inclusion of EVOH in comparison with stent without EVOH. There were almost no differences on the surface of the drug-eluting stent due to EVOH. The drug release was initially higher in the EVOH-containing stent compared to the stent without EVOH, and the degradation behavior of the polymer not affected by addition of EVOH. Cytotoxicity of the stent containing EVOH was evaluated. EVOH did not exhibit any cytotoxicity due to the degree of controlled release of the drug. Additionally, mechanical property of stent was confirmed by using EVOH and cellulose acetate butyrate (CAB). Radial force increased in stent with EVOH compared to without EVOH although flexibility was not changed. These results suggest that the application of EVOH to drug-eluting stents does not affect the degradation behavior of the stent surface and polymer, but it could be expected to suppress the sustained and excessive response of the drug by rapid release of the drug.

관상동맥 약물 방출 스텐트 삽입 후 스텐트 골절에 대한 임상결과 및 예후

김인수(In Soo Kim),한재복(Jae Bok Han),장성주(Seong Joo Jang) 대한방사선과학회(구 대한방사선기술학회) 2014 방사선기술과학 Vol.37 No.2

본 연구에서는 관상동맥 중재술로 관상동맥 약물방출 스텐트(drug-eluting stent, DES) 삽입 후 스텐트 골절에 대한 임상적 특성, 결과 및 예후에 대하여 연구하였다. 약물방출 스텐트 시술을 받고 추적 관상동맥조영술을 실시한 4,701명 환자에서 스텐트 골절이 발생한 환자는 32명(남:여=19:13, 평균연령 62.44±9.8세, 0.68%)이었다. DES의 종류별 스텐트 골절의 빈도는 SES(sirolimus- eluting stents) 19(59.4%), PES(paclitaxel-eluting stents) 9명(28.1%), BES(biolimus A9-eluting stents) 2명(6.3%), EES(everolimus-eluting stents) 1명(3.1%), EPC(endothelial progenitor cell capture stent) 1명(3.1%), ZES(zotarolimus-eluting stents) 0명(0%) 이었다. 표적 병변은 우관상동맥 13명(40.6%) 좌전하행지 16명(50.0%), 좌회선지 3명(9.4%)이었다. 각 혈관의 병변 형태는 복잡병변인 B2, C형이 25명(69.4%)이었다. 스텐트 골절 환자 중 스텐트 내 협착은 17명(53.1%)이었으며, 스텐트 골절 병변에 대한 치료는 내과적 관찰 16명(50.0%), 동종의 관상동맥 DES 시술 3명(9.4%), 이종의 관상동맥 DES 시술 10명(31.3%), 관상동맥 풍선 확장술 3명(9.4%)이었다. 추적검사에서는 32.9±12.4개월 동안 스텐트 골절로 인한 사망을 포함한 심장사는 발생하지 않았다. 결론적으로 관상동맥 중재술로 관상동맥 DES를 시술받은 추적관찰 대상 환자에서 3.7년 추적관찰 기간동안 스텐트 골절 발생률은 0.68%로 나타났으며, PES보다 SES에서 많은 발생 빈도를 보였다. 좌전하행지와 복잡병변에 대한 시술 후 스텐트 골절이 많이 발생하였다. 또한 스텐트 골절 정도와 협착 병변이 중대한 경우에만 관상동맥 중재술을 실시하였으며, 추적관찰 기간 중 스텐트 골절이 있는 환자는 병용 항혈소판 요법을 지속적으로 투여하였다. 특히 사망을 포함한 주요 심장사건에 관련하여 스텐트 골절과 연관된 심장사의 발생률은 매우 낮은 것으로 나타났다. 본 연구를 통해서 스텐트가 가지고 있는 특성 스텐트 디자인이 폐쇄형(closed cell) 디자인 SES에서 발생 빈도가 높음을 제시함으로써 스텐트 개발에 도움이 될 거라 판단된다. Many studies have suggested that in the era of Drug-Eluting Stents(DES) are one of the causes of In-Stent Restenosis(ISR) of Stent Fracture(SF). The present study sought to evaluate clinical characteristics of patients with stent fracture after successful DES implantation. The 4,701 patients were selected for analysis who underwent a follow-up coronary angiography irre-spective of ischemic symptoms. The overall incidence of SF was 32 patients(male:female=19:13, Av. age 62.44±9.8year, 0.68%). Fractures of Sirolimus-Eluting Stents(SES), Paclitaxel-Eluting Stents(PES), Biolimus A9-Eluting Stents(BES), Everolimus-Eluting Etents(EES), Endothelial Progenitor Cell Capture Stent(EPC) and Zotarolimus-Eluting Stents(ZES) are accounted for 19(59.4%), 9(28.1%),2(6.3%),1(3.1%),1(3.1%)and 0(0%) respectively. SF developed in the left Anterior Dscending(LAD) artery in 16 patients(50%) and in complex(type B2, C) lesions in 25 patients(69.4%). Ten patients were treated with heterogenous DES, the rest being treated with either homogenous DES(3 patients), plain old balloon angioplasty(3 patients), or conservative medical treatment(17 patients). None of the patients with SF suffered from cardiac death dur-ing a follow-up period of 32.9±12.4 months. The overall rate of DES fracture over up to 3.7 years of follow-up was 0.68% with higher incidence in SES than in PES. SF frequently occurred in the LAD artery and in complex lesions. Of the patients with SF, coronary intervention was performed only when the binary restenosis lesion was significant. During the follow-up, patients with SF have continued on combination antiplatelet therapy. There is a very low rate of major adverse cardiac events(post-detection of SF), especially cardiac death associated with SF.

A Case of Stent Strut Fracture of a Paclitaxel-Eluting Stent at the Time of Stent Implantation in a Complex Coronary Lesion

이현숙,허승호,남창욱,조윤경,김형섭,한성욱,김권배,김윤년 대한심장학회 2008 Korean Circulation Journal Vol.38 No.7

Several cases of stent strut fractures (SSFs) have recently been reported following drug-eluting stent (DES) implantation Although SSF is a rare complication, it has been suggested to be a cause of restenosis. To date, a number of cases of stent fracture have been associated with sirolimus-eluting stents and they occurred from 2 days to about 2 years after the initial procedure. We report here on a case of paclitaxel-eluting stent fracture at the time of stent placement in a calcified coronary lesion. Several cases of stent strut fractures (SSFs) have recently been reported following drug-eluting stent (DES) implantation Although SSF is a rare complication, it has been suggested to be a cause of restenosis. To date, a number of cases of stent fracture have been associated with sirolimus-eluting stents and they occurred from 2 days to about 2 years after the initial procedure. We report here on a case of paclitaxel-eluting stent fracture at the time of stent placement in a calcified coronary lesion.

Everolimus-Eluting Xience V/Promus Versus Zotarolimus-Eluting Resolute Stents in Patients With Diabetes Mellitus

Park, K.W.,Lee, J.M.,Kang, S.H.,Ahn, H.S.,Kang, H.J.,Koo, B.K.,Rhew, J.Y.,Hwang, S.H.,Lee, S.Y.,Kang, T.S.,Kwak, C.H.,Hong, B.K.,Yu, C.W.,Seong, I.W.,Ahn, T.,Lee, H.C.,Lim, S.W.,Kim, H.S. Elsevier 2014 JACC. Cardiovascular interventions Vol.7 No.5

Objectives: This study sought to compare everolimus-eluting stents (EES) versus Resolute zotarolimus-eluting stents (ZES) in terms of patient- or stent-related clinical outcomes in an ''all-comer'' group of patients with diabetes mellitus (DM) who underwent percutaneous coronary intervention. Background: DM significantly increases the risk of adverse events after percutaneous coronary intervention. The efficacy and safety of second-generation drug-eluting stents, in particular EES versus ZES, in patients with DM have not been extensively evaluated. Methods: Patients with DM (1,855 of 5,054 patients, 36.7%) from 2 prospective registries (the EXCELLENT [Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting] registry and RESOLUTE-Korea [Registry to Evaluate the Efficacy of Zotarolimus-Eluting Stent]) who were treated with EES (n = 1,149) or ZES (n = 706) were compared. Stent-related outcome was target lesion failure (TLF), and patient-oriented composite events were a composite of all-cause mortality, any myocardial infarction, and any revascularization. Results: Despite a higher risk patient profile in the ZES group, both TLF (43 of 1,149 [3.7%] vs. 25 of 706 [3.5%], p = 0.899) and patient-oriented composite events (104 of 1,149 [9.1%] vs. 72 of 706 [10.2%], p = 0.416) were similar between the EES and ZES in patients with DM at 1 year. In those without DM, EES and ZES also showed comparable incidence of TLF (39 of 1,882 [2.1%] vs. 33 of 1,292 [2.6%], p = 0.370) and patient-oriented composite events (119 of 1,882 [6.3%] vs. 81 of 1,292 [6.3%], p = 0.951), which were all significantly lower than in the DM patients. These results were corroborated by similar findings from the propensity score-matched cohort. Upon multivariate analysis, chronic renal failure was the most powerful predictor of TLF in DM patients (hazard ratio: 4.39, 95% confidence interval: 1.91 to 10.09, p < 0.001). Conclusions: After unrestricted use of second-generation drug-eluting stents in all-comers receiving percutaneous coronary intervention, both EES and ZES showed comparable clinical outcomes in the patients with DM up to 1 year of follow-up. DM compared with non-DM patients showed significantly worse patient- and stent-related outcomes. Nonetheless, overall incidences of TLF were low, even in the patients with DM, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents in this high-risk subgroup of patients.

The assessment of the performance of drug-eluting stent using computational fluid dynamics

서태원,Abdul I. Barakat 한국유변학회 2009 Korea-Australia rheology journal Vol.21 No.4

Numerical investigations have been conducted on the assessment of the performance of drug-eluting stent. Computational fluid dynamics is applied to investigate the flow disturbances and drug distributions released from the stent in the immediate vicinity of the given idealized stent in the protrusion into the flow domain. Our simulations have revealed the drug concentration in the flow field due to the presence of a drug-eluting stent within an arterial segment. Wall shear stress increases with Reynolds number for a given stent diameter, while it increases with stent diameter for a given Reynolds number. The drug concentration is dependent on both Reynolds number and stent geometry. In pulsatile flow, the minimum drug concentration in the zone of inter-wire spacing occurs at the maximum acceleration of the inlet flow while the maximum drug concentration gains at the maximum deceleration of the inlet flow. These results provide an understanding of the flow physics in the vicinity of drug-eluting stents and suggest strategies for optimal performance of drug-eluting stent to minimize flow disturbance.

The assessment of the performance of drug-eluting stent using computational fluid dynamics

Seo, Tae-Won,Barakat, Abdul I. The Korean Society of Rheology 2009 Korea-Australia rheology journal Vol.21 No.4

Numerical investigations have been conducted on the assessment of the performance of drug-eluting stent. Computational fluid dynamics is applied to investigate the flow disturbances and drug distributions released from the stent in the immediate vicinity of the given idealized stent in the protrusion into the flow domain. Our simulations have revealed the drug concentration in the flow field due to the presence of a drug-eluting stent within an arterial segment. Wall shear stress increases with Reynolds number for a given stent diameter, while it increases with stent diameter for a given Reynolds number. The drug concentration is dependent on both Reynolds number and stent geometry. In pulsatile flow, the minimum drug concentration in the zone of inter-wire spacing occurs at the maximum acceleration of the inlet flow while the maximum drug concentration gains at the maximum deceleration of the inlet flow. These results provide an understanding of the flow physics in the vicinity of drug-eluting stents and suggest strategies for optimal performance of drug-eluting stent to minimize flow disturbance.

스텐트 재협착 병변에서 약물코팅 풍선카테터과 약물용출 스텐트의 예후 분석

이두환,송종남,박신의,최남길,한재복,김인수 한국방사선학회 2019 한국방사선학회 논문지 Vol.13 No.3

Although the development of Drug-eluting stent (DES) improved the ISR significantly more than the Bare metal stent (BMS), the coronary stent restenosis (ISR) treatment still has a high recurrence rate. This study is compared the efficacy of DEB with that of DES implantation in patients with ISR. Among 4,316 patients who underwent coronary stent implantation at the Chonnam National University Hospital between November 2012 and December 2016, 187 patients developed ISR on follow-up coronary angiography (66.3 ± 11.0 years, 123 males) were enrolled and divided into two groups according to revascularization method as group I (DEB group; n= 127) and group II (DES group; n= 60). Primary end point was defined as major adverse cardiac events (MACEs), composite of cardiac death (CD), myocardial infaction (MI), target lesion revascularization (TLR) and stent thrombosis (ST) during two-year follow-up between the two groups. There were no differences in the baseline characteristics and angiographic findings except that prevalence of device length was shorter (21.1 ± 5.3 vs. 25.3 ± 9.6 mm, p<0.002) in group I.Two-year MACE were not different in the two groups (8.7%vs.10.0%, p=0.789). The incidences of cardiac death (0%vs.0%, p=1.000), MI (1.6%vs.6.7%, p=0.085), TLR(8.7% vs. 10.0%, p=0.789) and ST (0% vs. 0%, p=1000). DEB demonstrated comparable risk reduction for MACEs compared with DES in patients with ISR during two-year follow-up. DEB might be good alternative for the treatment of ISR in patients with ISR 약물용출 스텐트(drug-eluting stents, DES)는 일반 금속 스텐트에 비하여 재협착을 현저하게 줄였지만, 여전히 관상동맥 스텐트 재협착은 비율이 높다. 2012년 11월부터 2016년 12월까지의 일 대학교병원 심혈관센터에서 경피적 관상동맥 스텐트 삽입술 후 관상동맥 조영술에서 스텐트 재협착 환자 187명 그룹 I (약물코팅 풍선카테터 사용, n=127명), 그룹 II (약물용출 스텐트 사용, n=60명)로 분류하여 치료효과, 주요심장사건, 사망 발생률, 심근경색, 표적병변 재개통술 그리고 스텐트 혈전등을 2년 동안 추적 분석하였다. 임상적 특성는 두 그룹간 차이는 없었고(21.1 ± 5.3 vs. 25.3 ± 9.6 mm, p<0.002), 혈관조영검사에서 약물코팅 풍선카테터 사용 그룹에서 스텐트 재협착 길이가 짧았다. 주요심장사건은 8.7%vs.10.0%, p=0.789, 사망발생률 0%vs.0%,p=1.000, 심근경색 1.6%vs.6.7%, p=0.085, 표적병변 재개통술 8.7% vs. 10.0%, p=0.789 그리고 스텐트 혈전증 0% vs. 0%, p=1000에서 양군 간에 차이를 보이지 않았다. 약물코팅 풍선카테터가 약물방출 스텐트와 비교하여 2년 추적 검사 결과 주요심장사건에서 차이가 없었고, 약물코팅 풍선카테터는 스텐트 재협착 병변에서 약물방출 스텐트와 함께 선택할 수 있는 좋은 치료방법이라고 사료된다.

Intravascular imaging analysis of a drug-eluting balloon followed by a bare metal stent compared to a drug-eluting stent for treatment of de novo lesions

최원석,채인호,박진주,김선화,강시혁,오일영,윤창환,조영석,연태진,최동주 대한내과학회 2019 The Korean Journal of Internal Medicine Vol.34 No.4

Background/Aims: After a study comparing drug-eluting stents (DESs) to sequential treatment with drug-eluting balloons (DEBs) and bare metal stents (BMSs), we retrospectively analysed strut malapposition and neointimal hyperplasia in de novo coronary lesions using optical coherence tomography (OCT) or intravascular ultrasonography (IVUS). Methods: We obtained OCT data from 16 patients (eight per group) and IVUS data from 40 patients (20 per group). OCT or IVUS was performed after the index procedure and after 9 months. Parameters including obstruction volume due to neointimal hyperplasia (neointimal hyperplasia volume/stent volume, %), strut malapposition (% of malapposed struts), and intra-individual inhomogeneity of in-stent restenosis were compared. Results: Although obstruction volume due to neointimal hyperplasia was significantly higher in the DEB-BMS group (14.90 ± 15.36 vs. DES 7.03 ± 11.39, p = 0.025), there was no difference in strut malapposition between the two groups (DEB-BMS 1.99 ± 5.37 vs. DES 0.88 ± 2.22, p = 0.856). The DEB-BMS group showed greater intra- individual inhomogeneity of in-stent restenosis pattern than the DES group. Conclusions: Treatment with DEB followed by BMS failed to improve strut malapposition despite higher in-stent neointimal growth, probably because of the inhomogeneous inhibition of in-stent neointimal hyperplasia by DEB. DEB technology should be improved to obtain even drug delivery to the vessel wall and homogeneous prevention of neointimal growth comparable to contemporary DES.

<i>In vitro</i> and <i>in vivo</i> evaluation of a novel polymer-free everolimus-eluting stent by nitrogen-doped titanium dioxide film deposition

Park, Dae Sung,Bae, In-Ho,Jeong, Myung Ho,Lim, Kyung Seob,Sim, Doo Sun,Hong, Young Joon,Lee, So-Youn,Jang, Eun Jae,Shim, Jae-Won,Park, Jun-Kyu,Lim, Han Chul,Kim, Han Byul Elsevier 2018 Materials Science and Engineering C Vol.91 No.-

<P><B>Abstract</B></P> <P>Inflammation and thrombosis are linked to the use of polymer-based drug-eluting stents (DES). The aim of this study was to develop a polymer-free everolimus (EVL)-eluting stent using nitrogen-doped titanium dioxide (N-TiO<SUB>2</SUB>) and verify its efficacy by <I>in vitro</I> and <I>in vivo</I> assessment in a porcine coronary model. Various analytical approaches such as scanning electron microscopy and atomic force microscopy, electron spectroscopy, Fourier transform infrared spectrometry and contact angle measurement were employed for the characterization. As a part of biocompatibility assessment, platelet adhesion and smooth muscle cell (SMC) proliferation were examined. Bare metal stent (BMS), N-TiO<SUB>2</SUB> stent, everolimus-eluting N-TiO<SUB>2</SUB> (N-TiO<SUB>2</SUB>-EVL) stent, and commercialized EVL-eluting stent (EES) were randomly placed in forty coronary arteries in twenty pigs. After four weeks of implantation, the stents were subjected to histological and quantitative analysis. The N-TiO<SUB>2</SUB> film used in this study was well coated without any cracks or peeling. Surface hydrophilicity (88.8% of angle decrement) could be associated with the decrease in surface roughness post N-TiO<SUB>2</SUB> deposition (37.0%). The platelet adhesion on the N-TiO<SUB>2</SUB> surfaces was less than that on the BMS surface. The proliferation of SMC was suppressed in the N-TiO<SUB>2</SUB>-EVL group (30.2%) but not in the BMS group. In the animal study, the percent area restenosis was significantly decreased in the N-TiO<SUB>2</SUB>-EVL group compared to that in the BMS group. The results (BMS; 47.0 ± 11.00%, N-TiO<SUB>2</SUB>-EVL; 31.7 ± 10.50%, and EES; 29.1 ± 11.21%, <I>n</I> = 10, <I>p</I> < 0.05) were almost at par with those of the commercialized EVL-eluting stent. The introduction of N-TiO<SUB>2</SUB> deposition during fabrication of polymer-free DES may be an efficient accessorial process for preventing in-stent restenosis and thrombosis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> N-TiO<SUB>2</SUB> surfaces can help to reduce the platelet adhesion. </LI> <LI> In porcine model, N-TiO<SUB>2</SUB> everolimus decreased in-stent restenosis and fibrin deposition. </LI> </UL> </P>