First-generation Sirolimus-eluting Stents Research Articles

Ten-year clinical outcomes from a randomized trial comparing new-generation everolimus-eluting stent versus first-generation Sirolimus-eluting stent: Results from the RESET extended study.

New-generation drug-eluting stents (DES) achieved technological innovations and reported clinical advantages as compared with first-generation DES in clinical trials with 3-5 years follow-up. However, detailed clinical outcome data in very long-term follow-up is still scarce. To evaluate 10-year clinical outcomes after first- and new-generation DES implantation. In this extende follow-up study of the RESET, which is a largest randomized trial comparing everolimus-eluting stent (EES) with Sirolimus-eluting stent (SES), the study population consisted of 2892 patients from 84 centers. The primary efficacy and safety endpoints were target lesion revascularization (TLR) and a composite of death or myocardial infarction (MI), respectively. Complete 10-year follow-up was achieved in 87.9% of patients. Cumulative 10-year incidences of TLR and non-TLR were not significantly different between EES and SES (13.9% vs. 15.7%, Log-rank p = 0.20, and 33.4% vs. 31.3%, Log-rank p = 0.30). The cumulative 10-year incidence of death/MI was also not significantly different between the groups (32.5% vs. 34.4%, Log-rank p = 0.18). Cumulative 10-year incidence of definite stent thrombosis was numerically lower in EES than in SES (1.0% vs. 1.7%, Log-rank p = 0.16). The lower risk of EES relative to SES was significant for a composite endpoint of target lesion failure (TLF: 19.6% vs. 24.9%, Log-rank p = 0.001) and target vessel failure (TVF: 26.7% vs. 31.4%, Log-rank p = 0.006). During 10-yearof follow-up, the risks for primary efficacy and safety endpoints were not significantly different between new-generation EES and first-generation SES, although EES compared with SES was associated with a lower risk for composite endpoints such as TLF and TVF.

Comparison of Different Types of Drug-Eluting Stents for De Novo Long Coronary Artery Lesions.

Outcomes of percutaneous coronary intervention for diffuse long lesions remain relatively unfavorable. Prior clinical trials investigated the relative efficacy and safety of different types of drug-eluting stents (DES) in long lesions. This study sought to compare the relative performance of different types of DES for de novo long (≥25mm) coronary artery lesions. Using a pooled analysis of individual data of 1,450 patients from 3 randomized clinical trials, we compared angiographic and clinical outcomes of 5 different types of DES: 224 patients with cobalt-chromium everolimus-eluting stents (EES), 255 with platinum-chromium EES, 250 with Resolute zotarolimus-eluting stents, 245 with biodegradable polymer biolimus-eluting stents, and 476 with first-generation sirolimus-eluting stents (SES). The primary endpoint was in-segment late lumen loss at 9months. The primary endpoint was not significantly different between 4 second-generation DES and 1 first-generation SES (0.17 ± 0.41mm in cobalt-chromium EES; 0.11 ± 0.37 in platinum-chromium EES: 0.14 ± 0.38 in Resolute zotarolimus-eluting stents; 0.14 ± 0.38 in biodegradable polymer biolimus-eluting stents; or 0.10 ± 0.37 in SES, respectively, overall P = 0.38). Also, there were no significant between-group differences with respect to death, myocardial infarction, target-vessel revascularization, or stent thrombosis at 12months. In the multiple treatment propensity-score analysis, the risk of angiographic and clinical outcomes was also similar among several types of DES. In this patient-level pooled analysis, several second-generation DES showed similar angiographic and clinical outcomes in patients with de novo long coronary lesions. (Percutaneous Treatment of LONG Native Coronary Lesions With Drug-Eluting Stent-III [LONG-DES-III]; NCT01078038; Percutaneous Treatment of LONG Native Coronary Lesions With Drug-Eluting Stent-IV [LONG-DES-IV]; NCT01186094; and Everolimus-eluting [PROMUS-ELEMENT] vs. Biolimus A9-Eluting [NOBORI] Stents for Long-Coronary Lesions [LONG-DES-V]; NCT01186120).

＜Editors' Choice＞ Very long-term clinical outcomes after percutaneous coronary intervention for complex vs non-complex lesions: 10-year outcomes following sirolimus-eluting stent implantation.

ABSTRACTFew studies have reported the long-term outcomes (>10 years) following first-generation drug-eluting stent implantation. In this single-center retrospective study, we investigated the very long-term clinical outcomes after first-generation sirolimus-eluting stent (SES) implantation in patients with complex lesions. The study included 383 consecutive patients who underwent initial SES implantation between July 2004 and January 2006; 84 and 299 of these patients reported a history of percutaneous coronary intervention (PCI) for complex and noncomplex lesions, respectively. Complex PCI was defined as having at least one of the following features: left main trunk PCI, implantation of ≥3 stents, bifurcation lesions with implantation of 2 stents, total stent length >60 mm, or chronic total occlusion. The target lesion revascularization (TLR) rate was significantly higher in the complex PCI than in the noncomplex PCI group (29.4% vs 13.0%, P=0.001), and we observed a significant intergroup difference in the late TLR (>1 year) rates (21.6% vs 9.5%, P=0.008). Late TLR continued over 10 years at a rate of 2.4%/year in the complex PCI and 1.1%/year in the noncomplex PCI group. Cox regression analysis revealed that complex PCI was related to TLR both over 10 years (hazard ratio 2.29, P=0.003) and beyond 1 year (hazard ratio 2.32, P=0.01). Cardiac death was more common in the complex PCI than in the noncomplex PCI group, particularly 4 years after PCI (15.8% vs 7.5%, P=0.031). Sudden death was the major cause of cardiac death beyond 4 years in the complex PCI group. These data indicate that long-term careful follow-up is essential for patients implanted with SES, especially those treated for complex lesions.

Vascular Responses to First-Generation Sirolimus-Eluting Stents and Bare-Metal Stents Beyond 10 Years.

Background: There are limited data regarding differences in vascular responses between first-generation sirolimus-eluting stents (1G-SES) and bare-metal stents (BMS) >10 years after implantation.Methods and Results: We retrospectively investigated 223 stents (105 1G-SES, 118 BMS) from 131 patients examined by optical coherence tomography (OCT) >10 years after implantation. OCT analysis included determining the presence or absence of a lipid-laden neointima, calcified neointima, macrophage accumulation, malapposition, and strut coverage. Neoatherosclerosis was defined as having lipid-laden neointima. OCT findings were compared between the 1G-SES and BMS groups, and the predictors of neoatherosclerosis were determined. The median stent age at the time of OCT examinations was 12.3 years (interquartile range 11.0–13.2 years). There were no significant differences in patient characteristics between the 1G-SES and BMS groups. On OCT analysis, there was no difference in the prevalence of neoatherosclerosis and calcification between 1G-SES and BMS. Multivariable logistic regression analysis revealed that stent size, stent length, and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use were significant predictors of neoatherosclerosis. In addition, uncovered and malapposed struts were more prevalent with 1G-SES than BMS.Conclusions: After >10 years since implantation, the prevalence of neoatherosclerosis was no different between 1G-SES and BMS, whereas uncovered struts and malapposition were significantly more frequent with 1G-SESs.

Ten-year survival of patients undergoing coronary angioplasty with first-generation sirolimus-eluting stents and bare-metal stents

Compared to bare-metal stents (BMS), drug-eluting stents reduce stent restenosis and improve subsequent revascularization rates. The impact on patients’ survival has been the subject of debate. To assess the long-term (10-year) survival of patients undergoing percutaneous coronary intervention (PCI) with first-generation sirolimus-eluting stents (SES) in comparison with BMS. In a single-center registry, 600 consecutive patients who underwent successful PCI with SES between April 2002 and February 2003 were compared to 594 patients who underwent PCI with BMS between January 2002 and April 2002, just before the introduction of SES. Clinical and procedural data were collected at the time of intervention and 10-year survival status was assessed via the national life status database. All baseline characteristics were similar between groups except for smaller stent diameter (2.84±0.38 vs. 3.19±0.49 mm; p<0.001), greater stent length (18.50±8.2 vs. 15.96±6.10 mm; p<0.001) and higher number of stents per patient (1.95 vs. 1.46, p<0.001) in the SES group. Overall five- and 10-year all-cause mortality was 9.6% (n=110) and 22.7% (n=272), respectively. The adjusted HR for 10-year mortality in patients undergoing PCI with SES was 0.74 (95% CI 0.58-0.94; p=0.013), corresponding to a relative risk reduction of 19.8%. Other than PCI with BMS, older age, chronic kidney disease, chronic obstructive pulmonary disease and lower ejection fraction were independent predictors of 10-year mortality. To date, this is the longest follow-up study ever showing a potential survival benefit of first-generation sirolimus-eluting stents versus bare-metal stents, supporting prior observations on their sustained efficacy and safety relative to contemporary BMS. Em comparação com os stents de metal nulo (BMS), os stents com efeito de droga reduzem a restenose do stent e melhoram as taxas de revascularização subsequente. O impacto na sobrevivência dos pacientes tem sido objecto de debate. Avaliar a sobrevivência a longo prazo (10 anos) de pacientes submetidos a intervenção coronária percutânea (ICP) com stents sirolimus-eluting de primeira geração (SES) em comparação com a BMS. Num registo de um único centro, 600 pacientes consecutivos submetidos a ICP com SES entre Abril de 2002 e Fevereiro de 2003 foram comparados com 594 pacientes submetidos a ICP com BMS entre Janeiro de 2002 e Abril de 2002, imediatamente antes da introdução da SES. Os dados clínicos e processuais foram recolhidos no momento da intervenção e o estado de sobrevivência de 10 anos foi avaliado através da base de dados nacional do estado de vida. Todas as características de linha de base foram semelhantes entre os grupos, excepto para stents de menor diâmetro (2,84±0,38 vs. 3,19±0,49 mm; p<0,001), maior comprimento do stent (18,50±8,2 vs. 15,96±6,10 mm; p<0,001) e maior número de stents por paciente (1,95 vs. 1,46, p<0,001) no grupo SES. A mortalidade global de cinco e 10 anos por todas as causas foi de 9,6% (n=110) e 22,7% (n=272), respectivamente. A FC ajustada para mortalidade de 10 anos em pacientes submetidos a ICP com SES foi de 0,74 (95% CI 0,58-0,94; p=0,013), correspondendo a uma redução relativa do risco de 19,8%. Para além da ICP com SES, a idade avançada, doença renal crónica, doença pulmonar obstrutiva crónica e a fracção de ejecção inferior foram preditores independentes da mortalidade de 10 anos. Até à data, este é o estudo de seguimento mais longo a demonstrar um potencial benefício de sobrevida dos stents farmacológicos de primeira geração versus stents metálicos, em linha com estudos prévios que demonstram a sua eficácia e segurança quando comparados com SC contemporâneos.

Ten-year survival of patients undergoing coronary angioplasty with first-generation sirolimus-eluting stents and bare-metal stents

IntroductionCompared to bare-metal stents (BMS), drug-eluting stents reduce stent restenosis and improve subsequent revascularization rates. The impact on patients’ survival has been the subject of debate. ObjectiveTo assess the long-term (10-year) survival of patients undergoing percutaneous coronary intervention (PCI) with first-generation sirolimus-eluting stents (SES) in comparison with BMS. MethodsIn a single-center registry, 600 consecutive patients who underwent successful PCI with SES between April 2002 and February 2003 were compared to 594 patients who underwent PCI with BMS between January 2002 and April 2002, just before the introduction of SES. Clinical and procedural data were collected at the time of intervention and 10-year survival status was assessed via the national life status database. ResultsAll baseline characteristics were similar between groups except for smaller stent diameter (2.84±0.38 vs. 3.19±0.49 mm; p<0.001), greater stent length (18.50±8.2 vs. 15.96±6.10 mm; p<0.001) and higher number of stents per patient (1.95 vs. 1.46, p<0.001) in the SES group. Overall five- and 10-year all-cause mortality was 9.6% (n=110) and 22.7% (n=272), respectively. The adjusted HR for 10-year mortality in patients undergoing PCI with SES was 0.74 (95% CI 0.58-0.94; p=0.013), corresponding to a relative risk reduction of 19.8%. Other than PCI with BMS, older age, chronic kidney disease, chronic obstructive pulmonary disease and lower ejection fraction were independent predictors of 10-year mortality. ConclusionTo date, this is the longest follow-up study ever showing a potential survival benefit of first-generation sirolimus-eluting stents versus bare-metal stents, supporting prior observations on their sustained efficacy and safety relative to contemporary BMS.

7-Year Outcomes of a Randomized Trial Comparing the First-Generation Sirolimus-Eluting Stent Versus the New-Generation Everolimus-Eluting Stent: The RESET Trial

ObjectivesThe aim of this study was to compare 7-year outcomes between the first-generation sirolimus-eluting stent (SES) and the new-generation everolimus-eluting stent (EES) in a randomized clinical trial. BackgroundThere is a scarcity of very long-term (beyond 5 years) data from clinical trials investigating whether new-generation drug-eluting stents have clear clinical advantages over first-generation drug-eluting stents. MethodsRESET (Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial) is the largest randomized trial comparing EES with SES (NCT01035450). Among a total of 3,197 patients in the original RESET population from 100 centers, the present extended 7-year follow-up study was conducted in 2,667 patients from 75 centers after excluding those patients enrolled from centers that denied participation. Complete 7-year follow-up was achieved in 91.5% of patients. ResultsThe cumulative 7-year incidence of the primary efficacy endpoint of target lesion revascularization was not significantly different between EES and SES (10.2% vs. 11.7%; hazard ratio: 0.87; 95% confidence interval: 0.68 to 1.10; p = 0.24). The risk for the primary safety endpoint of death or myocardial infarction trended lower with EES than with SES (20.6% vs. 23.6%; hazard ratio: 0.85; 95% confidence interval: 0.72 to 1.005; p = 0.06). The cumulative 7-year incidence of definite stent thrombosis was very low and similar between EES and SES (0.9% vs. 1.0%; p = 0.82). The lower risk of EES relative to SES was significant for the composite secondary endpoint of target lesion failure (13.3% vs. 18.1%; hazard ratio: 0.72; 95% confidence interval: 0.59 to 0.88; p = 0.001). ConclusionsDuring 7 years of follow-up, the risk for target lesion revascularization was not significantly different between the new-generation EES and the first-generation SES.

Differential cutoff points and clinical impact of stent parameters of various drug-eluting stents for predicting major adverse clinical events: An individual patient data pooled analysis of seven stent-specific registries and 17,068 patients

BackgroundStent parameters (length and diameter) are well-known risk factors for adverse outcomes after percutaneous coronary intervention (PCI) with stenting. This study aimed to investigate the differential cutoff criteria and clinical impact of the length and diameter of various drug-eluting stents (DES) for predicting major cardiovascular events. MethodsUsing patient-level data from seven stent-specific, prospective DES registries, we evaluated 17,068 patients who underwent PCI with either various contemporary DES or first-generation DES between July 2007 and July 2015: 3053 treated with cobalt-chromium everolimus-eluting stents (CoCr-EES), 2976 with platinum-chromium EES (PtCr-EES), 2888 with Resolute zotarolimus-eluting stents (Re-ZES), 782 with Biomatrix biolimus-eluting stents (Bi-BES), 1868 with Nobori BES (No-BES), 1934 with Xience Prime cobalt-chromium EES (Pr-CoCr-EES), and 3567 with first-generation sirolimus-eluting stents (SES). Two clinical outcomes were assessed: target-vessel failure (TVF; a composite of cardiac death, target-vessel myocardial infarction, and target-vessel revascularization [TVR]) and TVR. ResultsStent length and stent diameter were important factors for predicting TVF or TVR in the entire cohort and in each DES cohort. For TVF risk prediction, the Youden index-based cutoff of stent length was highest with Bi-BES (45.0 mm) and lowest with No-BES (29.0 mm), and the cutoff of stent diameter was smallest with Pr-CoCr-EES (2.78 mm) and largest with No-BES (3.20 mm). For TVR risk prediction, the cutoff of stent length was the highest with PtCr-EES (48.0 mm) and the lowest with No-BES (29.0 mm), and the cutoff of stent diameter was smallest with CoCr-EES (2.72 mm) and largest with first-generation SES (3.30 mm). The 3-year TVF and TVR rates were substantially different according to the presence or absence of long lesions and small vessels determined using these cutoff points. ConclusionsFor contemporary PCI practice involving diverse types of DES, we identified differential cutoff points of stent length and diameter for predicting adverse clinical outcomes. The clinical impact of these stent parameters on outcomes and its magnitude varied according to different DES.Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01186133.

Coronary aneurysm formation after paclitaxel-coated balloon angioplasty for in-stent restenosis of first-generation sirolimus-eluting stent implanted 9years ago.

Coronary aneurysm formation after paclitaxel-coated balloon angioplasty for in-stent restenosis of first-generation sirolimus-eluting stent implanted 9years ago.

Initial pathological responses of second-generation everolimus-eluting stents implantation in Japanese coronary arteries: Comparison with first-generation sirolimus-eluting stents

BackgroundThe clinical benefit of second-generation drug-eluting stents (2nd DES) has been established, compared to first-generation drug-eluting stents (1st DES). However, pathological response after 2nd DES implantation remains unclear, particularly in the Japanese population. MethodsUsing specimens obtained by autopsy, we compared the histology between 2nd DES (41 sections) and 1st DES (38 sections) lesions within 1 year after stent implantation to evaluate early tissue reaction in Japanese patients. Stent segments were fixed with 10% buffered formalin and embedded in plastic, followed by hematoxylin–eosin and Masson's trichrome staining. Ratio of covered stent struts was calculated, and the area of fibrin deposition was morphometrically evaluated. The degree of inflammation around struts was examined semi-quantitatively (score 0–3). ResultsThe ratio of covered struts and mean fibrin area of 2nd DES were 0.69±0.05 and 658.0±173.4μm2. Those of 1st DES were 0.44±0.12 and 3107.5±1405.9μm2. In the 2nd DES, there was significantly less fibrin deposition and a higher covered struts ratio. The inflammation score was significantly lower in 2nd DESs compared to 1st DESs (1.02±0.16 vs. 1.19±0.54, p<0.05). ConclusionsHistopathological analysis showed advanced healing process in 2nd DES compared with 1st DES lesions. These results are consistent with clinical beneficial outcome of 2nd DES implantation.

Efficacy of everolimus-eluting stent implantation in patients with small coronary arteries (≤2.5 mm): outcomes of 3-year clinical follow-up

Previous studies have demonstrated that patients with small coronary artery lesions are at increased risk for late cardiac events after percutaneous coronary intervention. It remains uncertain whether second-generation drug-eluting stents have an advantage over first-generation drug-eluting stents in patients with small vessel lesions. Our aim was to compare in the 3-year clinical impact between second-generation everolimus-eluting stents (EES) and first-generation sirolimus-eluting stents (SES) in small vessel lesions. Four-hundred forty-four patients with small vessel lesions defined as reference diameter <2.5mm were treated with EES (237 patients, 265 lesions) or SES (207 patients, 220 lesions) and completed 3-year follow-up. We compared the major adverse clinical events (MACE) between the two groups. EES had no significant impact on the MACE rate compared with SES (4.6 vs. 7.2%, p=0.14). No significant differences were observed in the individual components of cardiac death (1.7 vs. 1.9%, p=0.78), myocardial infarction (1.3 vs. 3.4%, p=0.12), and ischemia-driven target lesion revascularization (2.3 vs. 4.6%, p=0.13) in EES and SES, respectively. Stent thrombosis, however, was significantly less in the EES group than in the SES group (0.7 vs. 3.4%, HR: 0.53, 95% CI 0.38-0.88, p<0.05). EES implantation did not significantly impact 3-year MACE rates compared to SES implantation in small vessel lesions. A significant reduction in the overall rate of stent thrombosis was observed in recipients of EES. While the SES group showed increasing rates of late and very late thrombosis, the EES group did not. EES offers a safe and effective treatment for small vessel lesions.

Angioscopic observation of extremely late arterial repair after intracoronary implantation of the first-generation sirolimus-eluting stents

BackgroundArterial repair delays after intracoronary implantation of Cypher sirolimus-eluting stents (SES), a representative first-generation drug-eluting stent. It remains unclear whether this delay would catch up with bare metal stents (BMS) during extremely long observation. The aim of this study was angioscopic observation of extremely late arterial repair after Cypher SES implantation. MethodsThirty-seven SES and 17 BMS were implanted into 22 and 9 patients with angina pectoris, respectively. Duration after implantation (DAI) ranged from 3 to 10.5years in both stents. Coronary angioscopy revealed neointimal stent coverage (NSC), presence of in-stent yellow plaque (YP), and mural thrombi (MT). NSC was semi-quantified into 4 grades (grade 0, no coverage; grade 1, thin coverage; grade 2, thick coverage; grade 3, fully embedded into neointima). ResultsIn the BMS-implanted lesions (BMSL), NSC was either grade 1 (24%) or grade 3 (74%), with rare YP and no MT. In the SES-implanted lesions (SESL), NSC was various, i.e. grade 0 (5%), grade 1 (59%), grade 2 (22%), and grade 3 (14%). YP and MT were observed in 27 and 24% of in SESL, respectively. In SESL with DAI>8years (n=5), NSC was either grade 1 (40%) or grade 3 (60%), although YP and MT were more frequently observed (60 and 40%, respectively). ConclusionsArterial repair after SES implantation caught up with BMS at around 8years with regards to NSC, although prevalence of YP and MT remained still greater in SESL than BMSL at extremely late phase.

Ten-year clinical outcomes after sirolimus-eluting stent implantation: Impact of an in-stent restenosis target lesion

Little is known about the long-term outcomes after first-generation sirolimus-eluting stent (SES) implantation. We aimed to investigate the clinical outcomes up to 10 years after SES implantation. The study population comprised 342 patients (504 lesions) who underwent SES implantation between January 2002 and December 2004. The median duration of follow-up was 3816 days (interquartile range [Q1-Q3], 3,705-3,883 days). The cumulative event rate of definite stent thrombosis was 3.9%. The cumulative rate of target lesion revascularization (TLR) at 1, 5, and 10 years was 8.7%, 18.8%, and 31.1%, respectively, and the annual rate of TLR was 3.1%. Clinically driven TLR occurred at relatively constant rate during 10 years (2.0% per year). In a multivariate analysis, higher body mass index, hemodialysis, in-stent restenosis (ISR) target lesion, and total stent length >30 mm were independent risk factors of TLR within 5 years. An independent risk factor of TLR beyond 5 years was ISR target lesion. Late TLR after SES implantation is a long-term hazard, lasting up to 10 years. The ISR target lesion is a risk factor of TLR during 10 years.

Serial Randomized Comparison of Strut Coverage of Everolimus- and First-Generation Sirolimus-Eluting Stents

BackgroundThere has not been sufficient data to evaluate the serial vascular healing pattern after everolimus-eluting stent (EES) implantation. Using optical coherence tomography, we compared serial changes in strut coverage of the EES and the first-generation sirolimus-eluting stent (SES). MethodsSixty patients were randomly assigned to receive either EES (n = 30) or first-generation SES (n = 30) for coronary artery disease. Serial optical coherence tomography evaluation immediately after the procedure, and 3- and 12-month follow-ups were performed in 50 patients with 54 stents (25 patients with 28 EES vs 25 patients with 26 SES). The percentage of uncovered struts was defined as the ratio of uncovered struts to total struts. The primary end point was the percentage of uncovered struts at 12-month follow-up. The secondary primary end point was the percentage of uncovered struts at the 3-month follow-up and the comparative percentage change (Δ) of uncovered struts at 3- and 12-month follow-ups of EES vs SES. ResultsThe percentage of uncovered struts was significantly lower in the EES group compared with the SES group (median value, 6.9%; interquartile range [IQR], 3.9-10.6% vs 11.1%; IQR, 5.5-29.4%, respectively) at the 3-month follow-up (P = 0.03), and at the 12-month follow-up (median value, 1.3%; IQR, 0.3-3.5% vs 3.6%; IQR, 1.0-9.4%; P = 0.02). The percentage Δ of uncovered struts from the 3- to the 12-month follow-up was similar (−7.0 ± 6.9% in EES vs −10.5 ± 13.6% in SES; P = 0.24). ConclusionsThe EES group showed more favourable stent strut coverage than the first-generation SES group at the early and late periods after stent implantation. These findings suggest that EES have a more beneficial effect for vascular healing.

0495: Clinical impact of second-generation everolimus eluting stent compared with first-generation sirolimus-eluting stent in diabetes mellitus patients

This study sought to study the second-generation everolimuseluting stent (EES) as compared with first-generation sirolimus-eluting (SES) in diabetes mellitus (DM) patients. All DM patients treated with EES or SES from January 2010, to December 2011 were included. The EES was compared with SES for the primary composite endpoint of clinically driven detected restenosis, definite stent thrombosis (ST), and all-cause mortality. In 226 percutaneous coronary intervention-treated DM patients, 353 stents were implanted (EES 118, SES 235). The EES was associated with significantly lower restenosis rates compared with SES (SES vs. EES: 16.7% vs. 2.8%, p=0,001, OR: 2.96; 95% CI: 1.57 to 5.57). Lower incidence of ST (SES vs. EES: 2,1% vs 0,8%, p=0,38) and mortality (SES vs. EES: 1,7 % vs 0%, p=0,15) was noted but did not reach statistical significance. In all-comer DM patients the use of EES was associated with improved outcomes compared with SES mainly driven by lower rates of clinically driven detected restenosis.

Abstract 13522: Vascular Healing in Drug-Eluting Stents: Differential Response of Limus-Eluting Stents in a Preclinical Model of Stent Implantation

Introduction: Recently, several clinical studies suggest that second-generation cobalt-chromium everolimus-eluting stents (CoCr-EES) lead to more favorable vascular healing than first-generation sirolimus-eluting stents (SES). However, it remains unclear the difference of vascular responses between CoCr-EES and SES. Methods: A total of 42 stents (14 bare-metal stents [BMS], 13 CoCr-EES, and 15 SES) were deployed in the iliac arteries of 31 Japanese White rabbits. Qquantitative real-time reverse-transcription polymerase chain reaction (QRT-PCR) analyses of the neointima were performed on days 30 and 90 after the stent implantation. Results: On day 30, the gene expression of the angiogenic growth factors (hepatocyte and basic fibroblast growth factors) and proteoglycans (decorin, biglycan and lumican) were more upregulated in the BMS than in the SES. However, at 90 days after stenting, the gene expression of proteoglycans and collagen was more upregulated in the SES than in the CoCr-EES and BMS. Conclusions: In contrast to CoCr-EES and BMS, SES strongly suppresses the vascular healing-related gene expression in the early phase, and then upregulates it in the late phase. These differences may lead to different clinical outcomes in humans.

Biodegradable Polymer-Based Sirolimus Coating Stent in a Porcine Coronary Restenosis Model

Durable polymer-based first-generation sirolimus-eluting stents (SES) reduce the risks of in-stent restenosis (ISR) and revascularization compared to bare metal stents (BMS). Therefore, drug eluting stents (DES), such as those using sirolimus and paclitaxel, have increasingly become available and used for the treatment of atherosclerotic coronary artery stenosis lesions. However, the permanent polymer in these DES can cause chronic inflammation and hypersensitive reactions in the stented artery after drug release. This may lead to delayed re-endothelialization, delayed arterial healing, and late stent thrombosis. In order to overcome the shortcomings of durable polymers, new DES using biodegradable polymers have been developed. DES with biodegradable polymers have been shown to be safe and effective in clinical trials. For example, biolimus A9-eluting stents (BES, Biomatrix, Biosensors Interventional Technologies Pte Ltd., Singapore) were developed as a third-generation drug eluting stent containing a bioabsorbadable polymer (PLA, poly-L-lactic acid) with the highly lipophilic sirolimus derivative biolimus A9. The objective of the present study was to evaluate a biodegradable polymer-based sirolimus coating on a novel bare-metal stent in a porcine coronary restenosis model.

First-generation versus second-generation drug-eluting stents in current clinical practice: updated evidence from a comprehensive meta-analysis of randomised clinical trials comprising 31 379 patients

BackgroundFirst-generation drug-eluting stents (DES) have become the most widely used devices worldwide for management of coronary artery disease. As remote follow-up data were becoming available, concerns emerged in regard to...

Balancing ischaemia and bleeding with dual antiplatelet therapy: a resolute endeavour

This editorial refers to ‘Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type’[†][1], by E. Camenzind et al. , on page 1932 and ‘Lack of association between dual antiplatelet therapy use and stent thrombosis between 1 and 12 months following Resolute zotarolimus-eluting stent implantation’[‡][2], by S. Silber et al. , on page 1949. The most devastating complication after stent implantation is sudden, thrombotic coronary occlusion, which results in myocardial infarction (MI) in 80–90% of patients and death in 20–30%. Dual antiplatelet therapy (DAPT) with aspirin and an ADP receptor antagonist is the foundation to prevent stent thrombosis (ST).1 Whereas drug-eluting stents (DES) are more effective than bare metal stents (BMS) in preventing restenosis and recurrent ischaemia, DES susceptibility to ST is increased by delayed endothelialization, polymer hypersensitivity, and other mechanisms,2 necessitating prolonged DAPT. Long-term DAPT may have additional benefits by preventing atherothrombotic events in patients with vascular disease.3 However, DAPT increases major bleeding, the occurrence of which is strongly associated with subsequent mortality.4 Striking the right balance between ischaemic and bleeding complications by fine-tuning the potency and duration of DAPT is essential to optimize DES outcomes. First-generation paclitaxel-eluting stents and sirolimus-eluting stents (SES) were approved based on the basis of double-blind randomized trials in which DAPT was used for 3–6 months. Thereafter, reports of late ST resulted in recommendations for DAPT for 1 year or longer, without randomized evidence to support this endorsement. These guidelines have been carried forward to newer generation DES, despite randomized trials demonstrating enhanced safety and effectiveness with these devices compared with their earlier … [1]: #fn-2 [2]: #fn-3

Late Adverse Events After Implantation of Sirolimus-Eluting Stent and Bare-Metal Stent

Late adverse events such as very late stent thrombosis (VLST) or late target-lesion revascularization (TLR) after first-generation sirolimus-eluting stents (SES) implantation have not been yet fully characterized at long term in comparison with those after bare-metal stent (BMS) implantation. Among 13 058 consecutive patients undergoing first percutaneous coronary intervention in the Coronary REvascularization Demonstrating Outcome study-Kyoto registry Cohort-2, 5078 patients were treated with SES only, and 5392 patients were treated with BMS only. During 7-year follow-up, VLST and late TLR beyond 1 year after SES implantation occurred constantly and without attenuation at 0.24% per year and at 2.0% per year, respectively. Cumulative 7-year incidence of VLST was significantly higher in the SES group than that in the BMS group (1.43% versus 0.68%, P<0.0001). However, there was no excess of all-cause death beyond 1 year in the SES group as compared with that in the BMS group (20.8% versus 19.6%, P=0.91). Cumulative incidences of late TLR (both overall and clinically driven) were also significantly higher in the SES group than in the BMS group (12.0% versus 4.1%, P<0.0001 and 8.5% versus 2.6%, P<0.0001, respectively), leading to late catch-up of the SES group to the BMS group regarding TLR through the entire 7-year follow-up (18.8% versus 25.2%, and 10.6% versus 10.2%, respectively). Clinical presentation as acute coronary syndrome was more common at the time of late SES TLR compared with early SES TLR (21.2% and 10.0%). Late catch-up phenomenon regarding stent thrombosis and TLR was significantly more pronounced with SES than that with BMS. This limitation should remain the target for improvements of DES technology.