Cypher Sirolimus-eluting Stent Research Articles

Ten-Year Outcomes of Sirolimus-Eluting Versus Zotarolimus-Eluting Coronary Stents in Patients With Versus Without Diabetes Mellitus (SORT OUT III)

We compared 10-year clinical outcomes in diabetes and nondiabetes patients treated with Endeavor zotarolimus-eluting (ZES) or Cypher sirolimus-eluting coronary stents (SES). A total of 1,162 patients were randomized to ZES (169 with diabetes) and 1,170 patients were randomized to SES (168 with diabetes). Patients were further stratified by diabetes status at the time of inclusion. A subgroup of patients with diabetes (n = 88) underwent angiographic re-evaluation 10 months after stent implantation. End points included a combined end point of death or myocardial infarction, and the individual end points of death, myocardial infarction, and revascularization. In patients with diabetes, we found no difference in the combined end point (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.53 to 1.24), death (OR 0.80, 95% CI 0.51 to 1.25), or in MI (OR 1.07, 95% CI 0.60 to 1.91). However, diabetics with ZES more frequently underwent coronary revascularization compared with SES patients (OR 1.93, 95% CI 1.05 to 3.66). In patients without diabetes, ZES and SES had similar 10-year rates of all end points (death: OR 1.13, 95% CI 0.93 to 1.39; MI: OR 0.80, 95% CI 0.61 to 1.05; revascularization: OR 0.81, 95% CI 0.61 to 1.09). Landmark analysis from 5 to 10 years showed no difference in outcomes between SES and ZES in either subgroup. In conclusion, at 10 years, SES and ZES performed similarly in patients with and without diabetes. Although coronary revascularization was more prevalent in diabetes patients with ZES, this may, in part, have been related to the angiographic follow-up that was offered to a subgroup of diabetes patients.

Comparative Efficacy of Sirolimus-Eluting Stents and Paclitaxel-Eluting Stents in East Asian Versus non-East Asian Patients: A Systematic Review & Meta-Analysis.

First-generation drug-eluting stents - such as the sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) - have become attractive options for percutaneous coronary intervention (PCI) and are still widely used in Asia. However, the effect of East Asian ethnicity on their efficacy remains unclear. Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials comparing the efficacy of the Cypher SES and Taxus PES. The outcomes of interest were stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), cardiac mortality, and all-cause mortality. Pooled 'East Asian' studies were compared against pooled 'non-East Asian' studies. SES significantly reduced stent thrombosis incidence in East Asian patients relative to PES. Irrespective of East Asian status, SES significantly reduced the incidence of TLR and TVR as compared to PES. The Cypher SES appears to be a superior choice over the Taxus PES for East Asian patients on account of its reduced risk of stent thrombosis in these patients. Irrespective of East Asian ethnic status, the Cypher SES also yields a significantly reduced incidence of TLR and TVR as compared to the Taxus PES. This article is protected by copyright. All rights reserved.

A randomized multicenter trial comparing the XIENCE everolimus eluting stent with the CYPHER sirolimus eluting stent in the treatment of female patients with de novo coronary artery lesions: The SPIRIT WOMEN study

BackgroundThe comparative performance of different drug-eluting stents (DES) among female patients has not been assessed in a randomized manner.ObjectivesThe SPIRIT Women Clinical Evaluation trial compared the durable polymer everolimus-eluting XIENCE stent (DP-EES) with the durable polymer sirolimus-eluting Cypher stent (DP-SES) in women undergoing percutaneous coronary intervention (PCI).MethodsA total of 455 female patients with stable CAD were randomly assigned to receive DP-EES (n = 304) or DP-SES (n = 151). The powered angiographic outcome of the trial was in-stent late lumen loss (LLL) at 9 months after the index procedure. Secondary angiographic end points included in-segment LLL, in-stent and in-segment binary restenosis and percent diameter stenosis. The primary clinical outcome was a composite of all-cause death, myocardial infarction (MI) or target vessel revascularization (TVR).ResultsAt 9-month follow-up, in-stent LLL was 0.19±0.38 mm and 0.11±0.37 mm in patients assigned to DP-EES and DP-SES, respectively. The one-sided upper 95% CI of the difference in in-stent LLL between the groups of 0.08 mm was 0.15 and therefore within the pre-specified non-inferiority margin of 0.17 mm (p for non-inferiority = 0.013). However, the test for superiority showed a borderline significant difference in terms of LLL between DP-EES and DP-SES (p for superiority = 0.044). There were no significant differences in binary restenosis (2.0% vs. 0.72%, p = 0.44) and percent diameter stenosis (14.97±12.17 vs. 13.36±10.82, p = 0.19). The rate of definite stent thrombosis at 12 months was lower in patients treated with DP-EES (0% vs. 2.0%, p = 0.036).ConclusionsAmong women undergoing PCI, DP-EES was associated with a small but probably clinically relevant increase in in-stent LLL at 9 months as compared to DP-SES and with a lower risk of definite stent thrombosis at 12 months.Trial registrationClinicalTrials.gov NCT01182428.https://clinicaltrials.gov/

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.

Abstract 652: Coronary Angioscopic Observation of Extremely Late Arterial Repair Catch-up after Sirolimus-eluting Stent Implantation

Sirolimus, a bio-suppressive drug, delays coronary arterial repair after implantation of Cypher sirolimus-eluting stents (SES), a representative first generation drug-eluting stent. It remains unclear, however, whether this delayed repair would catch up with bare metal stents (BMS) along extremely long observation. The aim of this study was angioscopic comparison of coronary arterial repair through a decade after implantation of SES and BMS. Enrolled were 31 patients with previous implantation of SES (n = 22) or BMS (n = 9). Duration after stent implantation (DSI) ranged from 3 to 10.5 years in both groups. Thirty-seven SES were implanted into the SES group and 17 BMS into the BMS group. The 54 stented segments were analyzed by quantitative coronary angiography (QCA) and non-obstructive coronary angioscopy (CAS). Under continuous flush of low-molecular-weight dextran, CAS visualized in-stent appearance, i.e. endothelial stent coverage (ESC), presence of yellow plaque (YP), and in-stent mural thrombi (ISMT). ESC was semi-quantified into 4 grades (grade 0, no coverage; grade 1, thin coverage; grade 2, decent coverage; grade 3, full coverage). QCA showed in-stent restenosis neither in SES- nor BMS-implanted segments (% diameter stenosis 14.8 ± 7.9 vs. 16.2 ± 8.2, respectively). Incidence of YP was 27% in SES and 6% in BMS (P < 0.03). Incidence of ISMT was 24% in SES, whereas never in BMS. ESC grade of BMS was either grade 1 (24%) or grade 3 (76%). SES-implanted segments were divided into two groups, i.e. DSI > 8 years (n = 5) and DSI < 8 years (n = 32). In the former (10.5 > DSI > 8 years), ESC grade of SES was either grade 1 (40%) or grade 3 (60%), being similar to ESC after BMS implantation. In the latter (8 > DSI > 3 years), however, ESC grade varied from grade 0 (6%), grade 1 (63%), grade 2 (25%), and grade 3 (6%). Incidence of YP or ISMT was 60% in the former, suggesting progression of neoatherosclerosis at extremely late phase. In conclusion, from the viewpoint of ESC, coronary arterial repair at SES implantation appeared to catch up with BMS at around 8 years later, although incidence of YP or ISMT remained still greater in SES than BMS at extremely late phase.

Comparison of Short- and Long-Term Cardiac Mortality in Early Versus Late Stent Thrombosis (from Pooled PROTECT Trials)

Studies have indicated varying mortality risks with timing of stent thrombosis (ST), but few have been adequately powered with prospective late follow-up. PROTECT randomized 8,709 subjects to either Endeavor zotarolimus-eluting or Cypher sirolimus-eluting stents. PROTECT Continued Access enrolled 1,018 patients treated with Endeavor zotarolimus-eluting stents. Subjects completed at least 4 and 3years of follow-up, respectively. ARC-defined definite and probable ST events were stratified by time from index procedure: early (≤30days), late (>30 and ≤360days), and very late (>360days). Rates of death and myocardial infarction were analyzed by ST timing. Median follow-up was 4.1years. There were 184 ST events (1.9%): 61 early, 27 late, and 96 very late. Patient and procedural characteristics were similar between timing groups. There was no difference in dual-antiplatelet therapy use at discharge (97%) or 1year (84%). Cardiac death in patients with ST at 4years occurred in 32.1% compared with 2.5% in patients without ST (p <0.001). Combined rates of cardiac death and myocardial infarction did not differ according to ST timing, yet early ST was more commonly associated with cardiac death at 4years than later ST (50.8% for early vs 18.5% for late vs 24.0% for very late; p <0.001). The relation between ST timing and outcomes did not differ between stent types. In conclusion, in prospective data, cardiac death was more common after early ST than later ST. Although ST remains infrequent, continued efforts to determine how to reduce ST, particularly within the first 30days, are warranted. (The PROTECT trial is registered with ClinicalTrials.gov, number NCT00476957.).

Outcomes following implantation of the Biolimus A9-eluting BioMatrix coronary stent: Primary analysis of the e-BioMatrix registry.

To assess the safety and efficacy of Biolimus A9-eluting stents (BES, BioMatrix™ and BioMatrix Flex™) in routine clinical practice. The LEADERS randomized trial has documented equivalent efficacy and superior safety of the BES when compared to a first generation Sirolimus-eluting Cypher(TM) stent. 5,472 patients from 57 centers, treated with BES, were enrolled in an international multicenter registry and followed clinically up to 2 years. Mean patient age was 63.2 ± 11 years, 24% of patients had diabetes, and 49.8% presented with an acute coronary syndrome. 99.3% of patients were discharged on dual antiplatelet therapy (DAPT), 83.3% remained on DAPT at 1 year and 30.6% at 2 years. The incidence of the composite primary end point [major adverse cardiac events (MACE) at 12 months] was 4.5% [cardiac death 0.9%, myocardial infarction 1.7%, clinically indicated target vessel revascularization (ci-TVR) 2.8%]. MACE incidence was 6.8% at 24 months (cardiac death 1.5%, myocardial infarction 2.4%, ci-TVR 4.3%). At 12 months, 32 patients (0.6%) had suffered at least one definite or probable stent thrombosis (ST), and 91 patients (1.7%) a major bleed (MB). Nine patients with ST (27.3%) and 7 patients with a MB (7.7%) died during the first year after the index procedure. Between 12 and 24 months after implantation, there were 18 (0.4%) additional MB and 8 (0.2%) additional ST. This large international cohort documents a low 12 and 24 months MACE incidence and a very low ST incidence in an unselected patient population undergoing BES implantation. The results are in keeping with those of the randomized controlled LEADERS trial. Even though ST with this stent was a rare event, it was still associated with significant mortality. MB remains a problem, and warrants improved tailoring of DAPT in recipients of drug eluting stents.

Long-Term Outcome of Sirolimus-Eluting and Zotarolimus-Eluting Coronary Stent Implantation in Patients With and Without Diabetes Mellitus (A Danish Organization for Randomized Trials on Clinical Outcome III Substudy)

We compared 5-year clinical outcomes in diabetic and nondiabetic patients treated with Endeavor zotarolimus-eluting stents (ZESs; Endeavor Sprint, Medtronic, Santa Rosa, California) or Cypher sirolimus-eluting stents (SESs; Cordis, Johnson & Johnson, Warren, New Jersey) coronary implantation. We randomized 2,332 patients to either ZESs (n = 1,162, n = 169 diabetic patients) or SESs (n = 1,170, n = 168 diabetic patients) stratified according to presence or absence of diabetes mellitus. End points included major adverse cardiac event (MACE), a composite of cardiac death, myocardial infarction, target vessel revascularization (TVR), and definite stent thrombosis. Among diabetic patients, MACE occurred more frequently in patients treated with ZESs than SESs (48 [28.4%] vs 31 [18.5%]; odds ratio [OR] 1.75, 95% confidence interval [CI] 1.05 to 2.93, p = 0.032) because of a higher rate of TVR (32 [18.9%] vs 14 [8.3%]; OR 2.57, 95% CI 1.32 to 5.02, p = 0.006). Among nondiabetic patients, ZES and SES had similar MACE rates at 5-year follow-up but SES was associated with a significantly higher risk of definite stent thrombosis (10 [1.0%] vs 23 [2.3%]; OR 0.43, 95% CI 0.20 to 0.91, p = 0.028). Moreover, during the last 4 years, ZES had fewer MACE, TVR, and stent thrombosis events among nondiabetic patients. In conclusion, SES remains superior to ZES in patients with diabetes throughout the 5-year follow-up, however, among nondiabetic patients, SES demonstrated a highly dynamic performance with favorable initial results followed by a late catch-up that included an overall higher risk of stent thrombosis.

Vascular healing and integration of a fully bioresorbable everolimus-eluting scaffold in a rabbit iliac arterial model.

We aimed to investigate a fully bioresorbable poly-l-lactide (PLLA) scaffold to assess vascular remodelling in comparison to a permanent polymeric metal DES. Twenty-five New Zealand white rabbits received an Absorb bioresorbable vascular scaffold (BVS, 1.0 and 1.1) or a CYPHER sirolimus-eluting stent (SES) in the iliac arteries. Twelve arteries were harvested at one month for scanning electron microscopy (SEM) analysis (BVS 1.1). The other implanted (BVS 1.0) arteries (n=32) were explanted at three, six and 36 months for light microscopic analysis. Re-endothelialisation assessed at one month was incomplete in both BVS and SES by SEM, with a trend towards greater coverage in SES (endothelialisation above strut: 32.2% vs. 60.6%, p=0.10). However, light microscopic analysis at later time points revealed greater endothelial coverage in BVS than in SES at 36 months (100.0% vs. 93.3%, p=0.05). Inflammation scores were comparable between arteries implanted with BVS and SES at three months (1.1 vs. 1.1, p=0.99), which decreased over time in the BVS implanted arteries (36 months: 0.0 vs. 0.2, p=0.05). At 36 months, BVS were completely resorbed, and resorption sites were replaced by connective tissue. BVS in the rabbit iliac artery model demonstrated ongoing vascular healing at three and six months, and complete vessel restoration, re-endothelialisation and no to minimal vascular inflammation at 36 months.

Abstract 458: Poor Progression of in-Stent Neoatherosclerosis in Patients With Everolimus-Eluting Stent Implantation: Coronary Angioscopic Observation

Very late stent thrombosis (VLST) is one of the most serious issues in the era of drug-eluting stents (DES). VLST has been attributed to delayed neointimal stent coverage (NSC) due to bio-suppressive drugs and vulnerability of in-stent neoatherosclerosis. The latter was recently proposed by pathologists as in-stent atherosclerotic lesions at chronic phase of coronary stenting. The aim of this study was angioscopic observation of in-stent vessel wall at 3 years after implantation of various generations of DES. Enrolled were 37 stented segments in 26 patients with stable angina (25 Cypher sirolimus-eluting stents, SES; 5 Endeavor zotarolimus-eluting stents, ZES; and 7 Xience V everolimus eluting stents, EES). Dual anti-platelet therapy, aspirin plus clopidogrel, had been continued since the stenting procedure. Coronary angiography showed no in-stent restenosis at chronic phase. Coronary angioscopy revealed the in-stent appearance; that is, grades of NSC [between score 0 (no coverage) and score 3 (full coverage)], presence of yellow plaque (YP), and subclinical stent thrombosis (ST). There was no significant difference in grades of NSC among SES, ZES, and EES (1.40±0.57, 1.71±0.77, and 1.80±0.75, respectively). YP and ST were not found in EES. YP was 24% and 20% in SES and ZES, respectively. ST was 20% both in SES and ZES. In conclusion, in-stent neoatherosclerosis appears not to progress at least for 3 years in EES-stented coronary segments, a representative of the second generation of DES.

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥ 3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957).

Atherosclerotic Change at One Year After Implantation of Endeavor Zotarolimus-Eluting Stent vs. Everolimus-Eluting Stent

Atherosclerosis progression is thought to be one of the mechanisms of late stent failure. Atherosclerosis progression is detected as yellow plaque formation on angioscopy. Cypher sirolimus-eluting stent has been reported to accelerate atherosclerosis progression, but the influence of Endeavor zotarolimus-eluting stent (Endeavor-ZES) or Xience everolimus-eluting stent (Xience-EES) on atherosclerosis has not been clarified. Therefore, we examined the serial changes in extent of atherosclerosis after the implantation of Endeavor-ZES or Xience-EES. Consecutive patients who received implantation of Endeavor-ZES (n=25) or Xience-EES (n=30) at de novo lesion of native coronary artery and who had successful angioscopy immediately after stent implantation (baseline) and at 1-year follow-up were included in the study. Change in the maximum yellow color grade (grade 0-3) of the stented segment from baseline to follow-up was examined and was compared between Endeavor-ZES and Xience-EES. The maximum yellow color grade decreased significantly from baseline to follow-up in Endeavor-ZES (1.6±1.1 vs. 0.4±0.8, P<0.001), but it did not change in Xience-EES (1.7±1.0 vs. 1.4±0.7, P=0.23). Although the maximum yellow color grade was not different between Endeavor-ZES and Xience-EES at baseline (P=0.72), it was significantly lower in Endeavor-ZES than in Xience-EES at follow-up (P<0.001). Atherosclerosis evaluated by yellow color of the plaque was significantly reduced at 1 year after Endeavor-ZES implantation, but was not changed after Xience-EES implantation.

Duration of dual antiplatelet therapy after implantation of the first-generation and second-generation drug-eluting stents

This study was carried out to determine the effect of the use of dual antiplatelet therapy (DAPT) for more than 12 months on long-term clinical outcomes in patients who had undergone a percutaneous coronary intervention with the first and second generations of drug-eluting stents (DES). The potential benefits of the use of DAPT beyond a 12-month period in patients receiving DES have not been established clearly. Moreover, it is also unclear whether the optimal duration of DAPT is similar for all DES types. A total of 2141 patients with coronary artery disease treated exclusively with Cypher sirolimus-eluting stents (SES) or Endeavor zotarolimus-eluting stents (ZES) were considered for retrospective analysis. The primary endpoint [a composite of all-cause mortality, nonfatal myocardial infarction (MI), and stroke] was compared between the 12-month DAPT and the >12-month DAPT group. A total of 1870 event-free patients on DAPT at 12 months were identified. The average follow-up was 28.2±7.4 months. The primary outcomes were similar between the two groups (4.1% 12-month DAPT vs. 1.9% >12-month DAPT; P=0.090). Incidences of death, MI, stroke, and target vessel revascularization did not differ significantly between the two groups. Subgroup analysis showed that in the patients with hypertension, >12-month DAPT significantly reduced the occurrence of death/MI/stroke compared with that in the 12-month DAPT group (P=0.04). In patients implanted with SES, the primary outcome was significantly lower with the >12-month DAPT group (5.2% 12-month DAPT vs. 1.6% >12-month DAPT; P=0.016), whereas in patients with ZES, the primary outcome was comparable between the two groups (2.3% 12-month DAPT vs. 2.0% >12-month DAPT; P=0.99). In our study, for all patients, >12-month DAPT in patients who had received DES was not significantly more effective than 12-month DAPT in reducing the rate of death/MI/stroke. Our findings, that patients who received SES benefit from >12-month DAPT whereas extended use of DAPT was not significantly more effective in those implanted with ZES, implied that the optimal duration of DAPT was different depending on different types of DES.

Sealing old plaques, seeding new plaques

In stent restenosis (ISR) is a heterogeneous phenomenon. The classical paradigm is neointimal proliferation in response to vessel wall injury often in combination with incomplete stent expansion. Drug-eluting stents (DES) have been designed to reduce or eliminate hyperplasia and in fact dramatically reduced restenosis and target lesion revascularization (TLR). The drawback of DES has been an increase in late and very late stent thrombosis, a potentially life-threatening complication considered a consequence of delayed and incomplete strut endothelialization. The article of Habara et al .1 challenges this concept by analysing in-stent restenosis with optical coherence tomography (OCT) in the first generation DES at different time intervals from the implantation. In this study of 86 sirolimus-eluting Cypher and paclitaxel-eluting Taxus stents ISR they described different neointimal patterns and assessed their prevalence at various time intervals from DES implantation. They demonstrated that restenotic …

The battle against stent thrombosis—to protect and to serve

Late on Sunday, Sept 3, 2006, Edoardo Camenzind took the podium at the end of a European Society of Cardiology (ESC) session in Barcelona, Spain, to present a meta-analysis of data from the pivotal drug-eluting stent approval trials with long-term follow-up. The main finding was that first generation drug-eluting stents were associated with higher rates of death and myocardial infarction than bare-metal stents—an effect most pronounced with the Cypher sirolimus-eluting stent (C-SES). 1 Camenzind E Steg PG Wijns W Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern. Circulation. 2007; 115: 1440-1455 Crossref PubMed Scopus (537) Google Scholar A similar risk of adverse mortality was detected in a second meta-analysis presented in the same session, 2 Nordmann AJ Briel M Bucher HC Mortality in randomized controlled trials comparing drug-eluting vs. bare metal stents in coronary artery disease: a meta-analysis. Eur Heart J. 2006; 27: 2784-2814 Crossref PubMed Scopus (440) Google Scholar and in the aftermath of heated debate—the repercussions of which were felt far beyond the confines of the meeting—the controversy came to be known as the “ESC Firestorm”. Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trialNo evidence of superiority of E-ZES compared with C-SES in definite or probable stent thrombosis rates was noted at 3 years. Time analysis suggests a difference in definite or probable stent thrombosis between groups is emerging over time, and a longer follow-up is therefore needed given the clinical relevance of stent thrombosis. Full-Text PDF

Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial

We sought to compare the long-term safety of two devices with different antiproliferative properties: the Endeavor zotarolimus-eluting stent (E-ZES; Medtronic, Inc) and the Cypher sirolimus-eluting stent (C-SES; Cordis, Johnson & Johnson) in a broad group of patients and lesions. Between May 21, 2007 and Dec 22, 2008, we recruited 8791 patients from 36 recruiting countries to participate in this open-label, multicentre, randomised, superiority trial. Eligible patients were those aged 18 years or older undergoing elective, unplanned, or emergency procedures in native coronary arteries. Patients were randomly assigned to either receive E-ZES and C-SES (ratio 1:1). Randomisation was stratified per centre with varying block sizes of four, six, or eight patients, and concealed with a central telephone-based or web-based allocation service. The primary outcome was definite or probable stent thrombosis at 3 years and was analysed by intention to treat. Patients and investigators were aware of treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT00476957. PROTECT randomised 8791 patients, of whom 8709 provided consent to participate and were eligible: 4357 were allocated to the E-ZES group and 4352 patients to the C-SES group. At 3 years, rates of definite or probable stent thrombosis did not differ between groups (1·4% for E-ZES [predicted: 1·5%] vs 1·8% [predicted: 2·5%] for C-SES; hazard ratio [HR] 0·81, 95% CI 0·58-1·14, p=0·22). Dual antiplatelet therapy was used in 8402 (96%) patients at discharge, 7456 (88%) at 1 year, 3041 (37%) at 2 years, and 2364 (30%) at 3 years. No evidence of superiority of E-ZES compared with C-SES in definite or probable stent thrombosis rates was noted at 3 years. Time analysis suggests a difference in definite or probable stent thrombosis between groups is emerging over time, and a longer follow-up is therefore needed given the clinical relevance of stent thrombosis. Medtronic, Inc.

3-Year Clinical Outcomes in the Randomized SORT OUT III Superiority Trial Comparing Zotarolimus- and Sirolimus-Eluting Coronary Stents

This study sought to examine the 3-year clinical outcomes in patients treated with the Endeavor (Medtronic, Santa Rosa, California) zotarolimus-eluting stent (ZES) or the Cypher (Cordis, Johnson & Johnson, Warren, New Jersey) sirolimus-eluting stent (SES) in routine clinical practice. The long-term clinical outcome in patients treated with ZES in comparison with SES is unclear. The authors randomized 2,332 patients to ZES (n = 1,162) or SES (n = 1,170) implantation. Endpoints included major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction, or target vessel revascularization; the individual endpoints of MACE; and definite stent thrombosis. At 3-year follow-up, the MACE rate was higher in patients treated with ZES than in patients treated with SES (148 [12.9%] vs. 116 [10.1%]; hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.04 to 1.69; p = 0.022). Target vessel revascularization was more frequent in the ZES group compared with the SES group (103 [9.1%] vs. 76 [6.7%]; HR: 1.40, 95% CI: 1.04 to 1.89; p = 0.025), whereas the occurrence of myocardial infarction (3.8% vs. 3.3%) and cardiac death (2.8% vs. 2.8%) did not differ significantly. Although the rate of definite stent thrombosis was similar at 3-year follow-up (1.1% vs. 1.4%), very late (12 to 36 months) definite stent thrombosis occurred in 0 (0%) patients in the ZES group versus 12 (1.1%) patients in the SES group (p = 0.0005). Although the 3-year MACE rate is higher in patients treated with ZES versus SES, our data highlight a late safety problem concerning definite stent thrombosis with the use of SES. This finding underscores the importance of long-term follow-up in head-to-head comparisons of drug-eluting stents. (Randomized Clinical Comparison of the Endeavor and the Cypher Coronary Stents in Non-selected Angina Pectoris Patients [SORT OUT III]; NCT00660478).

Pore Networks and Polymer Rearrangement on a Drug-Eluting Stent as Revealed by Correlated Confocal Raman and Atomic Force Microscopy

Drug release from and coating morphology on a CYPHER sirolimus-eluting coronary stent (SES) during in vitro elution were studied by correlated confocal Raman and atomic force microscopy (CRM and AFM, respectively). Chemical surface and subsurface maps of the SES were generated in the same region of interest by CRM and were correlated with surface topography measured by AFM at different elution times. For the first time, a direct correlation between drug-rich regions and the coating morphology was made on a drug-eluting medical device, linking drug release with pore formation, pore throats, and pore networks. Drug release was studied on a drug-eluting stent (DES) system with a multicomponent carrier matrix (poly(n-butyl methacrylate) [PBMA] and poly(ethylene-co-vinyl acetate) [PEVA]). The polymer was found to rearrange postelution because confluence of the carrier polymer matrix reconstituted the voids created by drug release.

Edge Effect From Drug-Eluting Stents as Assessed With Serial Intravascular Ultrasound

Several studies have demonstrated effective reduction of intimal hyperplasia within a drug-eluting stent (DES) when compared with a bare metal stent (BMS), thereby resulting in a lower incidence of target lesion revascularization.1–3 Restenosis at the stent edges, however, is not appreciably reduced by DES. Thus, to understand stent edge effect in DES, it is important to improve the efficacy of this technology. The concern that stent edge effects alter intimal hyperplasia in the stent but not at the edges has existed for many years, and often is described as the “candy wrapper phenomenon.” This phenomenon was first described in radioactive stents4,5 and is due to local inhibition of intimal growth and endothelial healing6 only within the stent. Many DES trials, therefore, sought to better understand the edge effect using intravascular ultrasound (IVUS) to assess the vessel response post stent implantation. Many studies have documented DES edge effect in older- and newer-generation DES. One challenge facing IVUS studies that assess DES edge effect is a high degree of patient-to-patient variability, along with potential variability among the different DES types. Because of these variables and the relatively small size of most sequential IVUS studies, there is no general consensus regarding stent edge effect in DES. We therefore reviewed the literature to find common findings and tendency. This review focused on 4 DES types approved by the United States Food and Drug Administration: the Cypher sirolimus-eluting stent (SES) (Cordis), the Taxus paclitaxel-eluting stent (PES) (Boston Scientific), the Endeavor zotarolimus-eluting stent (ZES) (Medtronic CardioVascular Inc.), and the XIENCE V everolimus-eluting stent (EES) (Abbott Vascular). ### Mechanical Edge Effect Post Stent Implantation Edge stenosis can occur from several different mechanisms: a vascular response from peri-stent vascular injury, plaque shift, and thrombus or hematoma formation post stent implantation. Before discussing DES and the impact of adding …

Five-year results of the Multicenter Randomized Controlled Open-Label Study of the CYPHER Sirolimus-Eluting Stent in the Treatment of Diabetic Patients with De Novo Native Coronary Artery Lesions (SCORPIUS) study: A German multicenter investigation on the effectiveness of sirolimus-eluting stents in diabetic patients

Because a delayed arterial healing response after drug-eluting stent implantation has raised concerns about safety in diabetic patients, long-term effects of treatment with sirolimus-eluting stent (SES), as compared with bare-metal stent (BMS), have to be established. The aim of the 5-year follow-up of the randomized, controlled, open-label multicenter SCORPIUS study was to assess long-term safety and efficacy of the CYPHER (Cordis, Johnson & Johnson, Bridgewater, NJ) SES in percutaneous coronary intervention of diabetic patients. A total of 190 patients with type 2 diabetes mellitus were randomized to receive either a SES (n = 95) or a BMS (n = 95). Dual-antiplatelet therapy (aspirin plus clopidogrel) was prescribed for at least 6 months. Clinical follow-up data were scheduled at 1, 8, and 12 months and 5 years. Treatment with SES resulted in a 16% decrease in the rate of major adverse cardiac events (36% vs 52%; hazard ratio 0.6, 95% CI 0.4-0.9; P = .02). This reduction in major adverse cardiac events with SES at 5 years was mostly attributable to a lower number of repeat target lesion revascularization (13% vs 29%; hazard ratio 0.4, 95% CI 0.2-0.7; P = .003). No differences between groups were observed for safety end points (all-cause mortality 21% vs 21%, cardiac death 15% vs 13%, repeat myocardial infarction 8% vs 9%, and stent thrombosis 5% vs 6%) at 5 years. The 5-year follow-up of the SCORPIUS trial demonstrates the long-term antirestenotic efficacy of SES in diabetic patients with significantly reduced target lesion revascularization and comparable rates of mortality, myocardial infarction, and stent thrombosis compared with BMS.