Sirolimus-eluting Stent Implantation Research Articles

A case report of very late stent thrombosis observed simultaneously in all three vessels 5 years after sirolimus-eluting stent implantation

A 67-year-old man with recent myocardial infarction underwent a total of five sirolimus-eluting stents (SES) implantation for three vessels stage by stage. A follow-up angiography showed no significant restenosis except one in the side branch. Thereafter, he had remained asymptomatic. Sixty-six months later, he had an acute myocardial infarction with cardiogenic shock due to simultaneous 3-vessel very late stent thrombosis (VLST). After successful percutaneous coronary intervention, final angiography revealed serious peri-stent contrast staining along with positive remodeling and grade V stent fracture. This rare case illustrates simultaneous 3-vessel VLST, associating with multiple SES-related problems, under continuation of aspirin and cilostazol.

Impact of early target lesion revascularization on long-term clinical outcomes after sirolimus-eluting stent implantation

Backgrounds: Whether early Target Lesion Revascularization (TLR) after percutaneous coronary intervention influences long-term clinical outcomes is little known. In this study, we evaluated the impact of TLR within one year after Sirolimus-Eluting Stent (SES) implantation on the long-term clinical outcomes. Methods: From January 2003 to August 2007, consecutive 2203 patients, excluding hemodialysis patients, underwent the first SES implantation. Of these patients, we evaluated 2101 patients who were able to be followed since one year after SES implantation, and compared the long-term clinical outcomes, including cardiac death, Myocardial Infarction (MI), any revascularization, TLR, and non-TLR revascularization, between the TLR within one year (1-year TLR, 218 patients) group and the non-TLR within one year (1-year non-TLR, 1883 patients) group. Results: The median follow-up duration was 2320 days (interquartile range, 2024-2544 days). There was no difference in the incidence of cardiac death between the 1-year TLR group and the 1-year non-TLR group (6.6% vs. 5.3%, p = 0.34; Figure A). The incidence of MI was also similar between the two groups (5.3% vs. 2.5%, p = 0.17; Figure A). All of the incidences of any revascularization, TLR, and non-TLR revascularization were much higher in the 1-year TLR group than in the 1-year non-TLR group (58.9% vs. 32.6%, p < 0.001; 48.1% vs. 19.4%, p < 0.001; 40.0% vs. 24.4%, p < 0.001; respectively; Figure B). ![Figure][1] Conclusions: Early TLR within one year after SES implantation was not associated with hard clinical outcomes including cardiac death and MI, but with the higher incidences of the following revascularization. [1]: pending:yes

No harmful effect of stem cell mobilization by granulocyte-colony stimulating factor on non-culprit coronary plaques after sirolimus-eluting stent implantation

Purpose: Previous studies have demonstrated that stem cell mobilization by granulocyte-colony stimulating factor (G-CSF) attenuates the endothelial dysfunction in mechanically disrupted animal artery models. However, some clinical studies have shown increased neointimal hyperplasia in patients who underwent bare metal stent implantation. Furthermore, the effect of stem cell mobilization on non-culprit plaques is unknown. The purpose of this study was to evaluate the effects of stem cell mobilization by G-CSF on non-culprit coronary plaques after sirolimus-eluting stent (SES) implantation. Methods: This double-blinded randomized placebo-control study (primarily designed to evaluate the effect of stem cell mobilization by G-CSF on endothelial function after SES implantation) assigned patients to the G-CSF group (n=50) or the placebo group (n=50). After successful SES implantation, the patients received subcutaneous injection of G-CSF (300 mg daily) or saline for 5 days. Follow-up angiography and intravascular ultrasound (IVUS) was performed 9 months after SES implantation. Plaque volume was measured by IVUS at non-culprit segments which were defined as more than 5mm proximal or distal from the stent. Percent change in plaque volume (ΔPV) of non-culprit segments between post-procedure and follow-up was evaluated. Results: Plasma CD34+ cell level did not differ between the 2 groups at baseline (0.94±0.55 vs. 0.93±0.68/μL, p = 0.96). It significantly increased after G-CSF injection (0.94±0.55 vs. 18.39±13.55/μL, p <0.001) but did not in the placebo group (0.93±0.68/μL vs. 1.35±2.36/μL, p = 0.22). No death or myocardial infarction was observed during follow-up. Follow-up IVUS was available in 39 G-CSF patients (78%) and 43 placebo patients (86%) (p = 0.30). There was no significant difference in ΔPV between both groups at proximal (-11.0±16.4% vs. -14.7±9.8%, p = 0.35) and distal (-5.1±28.6% vs. -4.9±17.3%, p = 0.97) non-culprit segments. Conclusion: Stem cell mobilization by G-CSF does not increase plaque volume at non-culprit coronary plaques after SES implantation.

Impact of polyvascular disease and chronic kidney disease on long-term cardiovascular outcomes after sirolimus-eluting stent implantation

Background: Polyvascular disease (PolyVD) and chronic kidney disease (CKD) have been known to be independent risk factors for cardiovascular events. We evaluated the association between PolyVD and CKD through long-term cardiovascular outcomes after sirolimus-eluting stent (SES) implantation in patients with each stage of CKD. Methods: A total of 1797 patients with CKD except hemodialysis patients who had undergone SES implantation from November 2002 to January 2007 and 6-year follow up were enrolled in this study. Estimated glomerular filtration rate (eGFR) was classified into three stages: mild (eGFR 60-89), moderate (eGFR 30-59), and severe (eGFR < 30) CKD. The 1797 patients were divided into two groups: those with PolyVD (276) and those without PolyVD (1521). The number of patients with each stage (with PolyVD vs. without PolyVD) was as follows: mild 94 (34%) vs. 780 (51%), moderate 155 (56%) vs. 635 (42%), and severe 27 (10%) vs. 106 (7%). Results: The patients with PolyVD were older and had more cardiovascular risk factors. In the patients with moderate and severe CKD, the patients with PolyVD had a higher incidence of major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, and target lesion revascularization) (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.06-1.91, p=0.019) than those without PolyVD. Kaplan–Meier estimates for MACE stratified according to the CKD severity are shown in the figure. In the only patients with PolyVD, those with both moderate (HR 1.92, 95% CI 1.08-2.98) and severe CKD (HR 4.13, 95% CI 1.93-8.85) had higher incidence rates of MACE, as compared with those with mild CKD. ![Figure][1] Kaplan-Meier estimates of MACE Conclusion: The impact of CKD on the long-term cardiovascular outcomes after SES implantation was different between patients with and without PolyVD. [1]: pending:yes

Rapamycin modulates anti- and pro-thrombotic gene expressions via Kruppel-like factor 2: in vitro studies

Purpose: Stent thrombosis (ST) is one of severe complications after sirolimus-eluting stent (SES) implantation. However, the underlying transcriptional mechanisms of this adverse effect have less been investigated. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with rapamycin and gene expression profiling including Krupple-like factor 2 (KLF2), tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), endothelial nitric oxide synthase (eNOS), thrombomodulin (TM), and mammalian target of rapamycin (mTOR) were determined. Cells infected with adenovirus-KLF2 (Ad-KLF2) were stimulated by rapamycin and the expressions of the preceding genes were also examined. At same time, the effects of cell lysates on blood clotting time were evaluated in vitro. Results: Rapamycin enhanced TF, PAI-1 but inhibited KLF2, eNOS and TM expressions in a dose-dependent manner, which were antagonized by FK-506, a competitor of rapamycin. Overexpression of KLF2 strongly reversed rapamycin-induced effects on preceding gene expressions. Meantime, KLF2 overexpression increased the time of blood clotting in vitro. Conclusion: Rapamycin resulted in an imbalance of anti- and pro- thrombotic gene expression profiling, which was reversed by overexpression of KLF2, suggesting that that the KLF2 pathway might be involved in ST after SES implantation.

The relationship between peri-stent contrast staining and positive remodeling after sirolimus-eluting stent implantation assessing with intravascular ultrasound and optical coherence tomography

Purpose: It was reported that peri-stent contrast staining (PSS) was one of abnormal vessel reactions including incomplete stent apposition (ISA) and multiple interstrut hollows (MIH) assessed with optical coherence tomography (OCT), meanwhile positive vessel remodeling could be regarded as one of mechanisms of ISA. The aim of this study was to clarify the relationship between PSS and positive remodeling. Methods: Between May 2008 and February 2010, we performed IVUS and OCT for 56 in-stent restenosis lesions after sirolimus-eluting stent implantation. We found PSS in 19 of the 56 lesions by coronary angiography. We examined the difference in IVUS parameters including external elastic membrane (EEM) area and remodeling index (RI) at PSS site between lesions with PSS and those without PSS. PSS is defined as contrast staining outside the stent contour extending to >20% of the stent diameter measured by quantitative coronary angiography. ISA was defined as separation of at least 1 stent strut from the vessel wall which is not related to a side branch, and MIH is defined as multiple hollows (the maximum depth >0.5 mm) existing between and outside well-apposed stent struts, assessed with OCT. The remodeling index (RI) was defined as the ratio of EEM area at PSS site to that at the proximal reference site, assessed with IVUS. Positive remodeling was defined as RI >1.05. Furthermore, we examined the difference in EEM area and RI at lesion site between lesions with and without ISA and MIH. Results: Patients were 45 men and 11 women, and the mean age was 70.1±8.3 years. The results are shown in the figure. ![Figure][1] The results assessed with IVUS and OCT Conclusions: PSS might be closely associated with the existence of positive remodeling, ISA, and MIH. [1]: pending:yes

Characteristics of angiographic Peri-Stent contrast Staining (PSS) on very late stent thrombosis after sirolimus-eluting stent implantation: morphological classification and antiplatelet therapy

Backgrounds: We previously reported that Peri-Stent contrast Staining (PSS) after Sirolimus-Eluting Stent (SES) was associated with subsequent Very Late Stent Thrombosis (VLST) in a cohort with larger number of patients and longer follow-up duration. However, real clinical characteristics of PSS on VLST remain unknown due to the small numbers of patients with PSS. Methods and results: The j-Cypher PSS substudy included 5712 patients (7838 lesions) with angiographic follow-up within 12 months after SES implantation in 19 participating centers. Late acquired PSS without TLR within 12 months was observed in 174 patients (3.3%) or 183 lesions (2.5%). We found association between VLST and morphologic classification of PSS, 6 out of 8 cases of VLST was segmental types of PSS. Progressive increase in the severity of PSS over time before the onset of VLST was observed in 4 lesions out of 8 lesions with VLST and PSS. Among patients with PSS, those patients who had subsequent VLST were less often had hypertension than those patients without subsequent VLST. Among lesions with PSS, lesion length was significantly longer in lesions with VLST than in lesions without VLST. In patients with PSS finding within the first year, cumulative incidence of VLST through 4 years after the index follow-up angiography was not significantly different between the 2 groups of patients either on or off thienopyridine at 1 year after initial SES implantation. ![Figure][1] Conclusions: Progressive increase in the severity of PSS over time and segmental types of PSS was associated with higher risks for subsequent VLST. Either on or off thienopyridine at 1 year after initial SES implantation was not associated with VLST in the patients with PSS. [1]: pending:yes

Evaluation of peri-stent contrast staining and stent fracture after sirolimus-eluting stent implantation by dual source computed tomography

Evaluation of peri-stent contrast staining and stent fracture after sirolimus-eluting stent implantation by dual source computed tomography

Differential responses of local coagulation after implantation of everolimus-eluting and zotarolimus-eluting stents compared with early-generation drug-eluting stents in patients with stable angina

Purpose: We have previously demonstrated local persistent hypercoagulability after sirolimus-eluting stent (SES) implantation by measuring plasma prothrombin fragment F1+2 (frF1+2) levels. The aim of this study is to examine local coagulation response after everolimus-eluting stent (EES) and zotarolimus-eluting stent (ZES) implantation compared with early-generation drug-eluting [SES and paclitaxel-eluting stent (PES)] and bare metal stents (BMS). Methods: Eighty-five patients who were treated about eight months earlier with stents to the mid-segment of the left anterior descending coronary artery, with no evidence of restenosis, were studied (EES:12, ZES:15, PES:18, SES:20, and BMS:20). We measured plasma levels of frF1+2 sampled in coronary sinus (CS) and sinus of Valsalva (V). The transcardiac frF1+2 gradients (ΔfrF1+2) were defined as CS level minus V level. Results: A larger percent diameter stenosis (%DS) was observed in the ZES and BMS groups than in the SES (17.1±13.2, 25.1±15.6 vs 7.1±16.5%, p<0.05, respectively). There were no significant differences in %DS among SES, PES, and EES groups (7.1±16.5, 10.5±15.2, 12.6±12.9%, NS). There were no significant differences in ΔfrF1+2 among BMS, ZES, and EES groups (4.7±13.4, 5.5±8.4, 3.3±11.7 pmol/l, NS). The ΔfrF1+2 was smaller in the ZES and EES group, and larger in the PES group than in the SES group (5.5±8.4, 3.3±11.7, 32.3±24.2 vs 23.4±21.1 pmol/l, p<0.05, respectively). The ΔfrF1+2 significantly correlated with the total stent length in the SES group (r=0.53, p<0.05), however, it did not correlate in the EES, ZES, and PES groups. Conclusions: A decreased response of local coagulation after ZES and EES implantation and an increased one after PES implantation were observed, as compared to SES implantation. These findings might be associated with lower strut thickness, unique characteristics of polymer, and lower cytotoxic effect of eluted drug in second-generation drug-eluting stents.

Endothelial vasomotor function after everolimus-eluting stent implantation

Background and aim: Several studies have reported some grade of endothelial dysfunction (ED) after sirolimus-eluting stent, paclitaxel-eluting stent and zotarolimus eluting stent implantation, but up to date, the effects of everolimus-eluting stent (EES) on endothelial vasomotor function are not well known. The aim of this study was to evaluate the grade of ED in patients with EES compared to patients with bare metal stent (BMS) implantation. Methods: Consecutive patients with successfully EES implantation were included in the experience. The control group consisted in 15 patients successfully treated with BMS. A coronary arteriography and an intracoronary acetylcholine (Ach) ED test were performed to all patients 6 months after stent implantation. Quantitative coronary angiography analysis was performed by two experienced operators evaluating changes in mean luminal diameter (MLD) of the segment distal to the stent after increasing doses of Ach. To minimize the potential influence of differences in baseline characteristics among groups, a general linear model was used to analyze the changes in MLD in response to intracoronary Ach infusion, unadjusted and adjusted by stent length, in-stent late loss and baseline MLD as covariates. Results: Fifteen patients with EES and 15 patients with BMS were included. EES group presented a MLD variation of 3.14% after Ach highest dose infusion. BMS group showed a variation of 2.35% with no statistically significant difference (3.14% vs 2.35% p >0.05) When the comparison was performed with adjusted data, (Figure 1) despite a numerical tendency of higher degree of vasoconstriction in EES group compared to BMS no statistically significant difference was found. ![Figure][1] Figure 1 Conclusions: EES implantation is not related with a higher ED grade compared to BMS implantation. [1]: pending:yes

Predictors of stent thrombosis from 30 days to 3 years after zotarolimus- vs sirolimus-eluting coronary stent implantation: an analysis from PROTECT

Predictors of stent thrombosis from 30 days to 3 years after zotarolimus- vs sirolimus-eluting coronary stent implantation: an analysis from PROTECT

Ten-year clinical follow-up after sirolimus-eluting stent (Cypher) implantation

Ten-year clinical follow-up after sirolimus-eluting stent (Cypher) implantation

Difference in outcomes after repeat PCI for sirolimus-eluting stent restenosis lesions with or without stent fracture

Background: Presence of stent fracture (SF) after sirolimus-eluting stent (SES) implantation has reported to be associated with an increased risk of in-stent restenosis and target lesion revascularization (TLR). Incidence of SF and the relevance to cardiovascular events are previously reported. But little is known about the outcomes after repeat DES implantation for SES restenosis lesion with SF. So this study compared the outcomes after repeat PCI for SES restenosis lesion with or without SF. Method: From April 2007 to August 2011, total 2020 lesions implanted SES during PCI at our hospital. Total 148 lesions, 7.3% had restenosis (defined as % diameter stenosis >50%) in follow up angiogram. One hundred seven lesions went to TLR, consisted of 75 lesions with repeat DES implantation and 32 lesions with balloon angioplasty alone. SF was defined as complete or partial separation of the stent as assessed by plain fluoroscopy and detected in 61 lesions of SES restenosis lesions. Thirty-three SES restenosis lesions with SF (SF group) and 42 SES restenosis lesions without SF (non SF group) were retrospectively evaluated re-restenosis rate during follow up after repeated implantation of DES. Result: Baseline characteristics were similar. One-year cumulative incidence of re-restenosis after repeat DES implantation for SF group and non SF group which calculated by Kaplan-Meier method were 68% and 36% (P=0.0332), respectively (Figure 1). ![Figure][1] Figure 1. One-year cumulative incidence of re-restenosis Conclusion: Restenosis lesions with SF had significantly high incidence of re-restenosis after repeat DES implantation. [1]: pending:yes

Five-year outcomes and late adverse events after sirolimus-eluting stent implantation for unprotected left main coronary artery disease

Background: The clinical guideline for unprotected left main (LM) disease has been updated and percutaneous coronary intervention (PCI) for LM disease has become a common procedure in daily clinical practice. Long-term clinical outcome, however, has not been adequately addressed yet, especially late adverse events beyond 1 year after stent implantation for LM disease. Methods and results: We evaluated long-term clinical outcome including late adverse events beyond 1-year after LM-PCI in consecutive 134 patients who received unprotected LM stenting with sirolimus eluting stents (SES) at Kyoto university hospital between September, 2004 and December, 2009. The mean clinical follow-up period of this study was 4.0±1.8 years. Late Adverse events were defined as sudden cardiac death, target-vessel myocardial infarction (MI), emergent revascularization for LM disease, and acute congestive heart failure (ACHF), which occurred beyond 1 year after stent implantation. The cumulative incidence of all-cause death, cardiac death, and target-lesion revascularization (TLR) for LM disease was 26.5%, 8.1%, and 12.9%, at 5 years after LM-PCI, respectively. The cumulative incidence of cardiac death was significantly higher in patients with 2 stenting technique compared to those with single stenting. Late adverse events were occurred in 6 patients. There are no late adverse events in patients with non-bifurcation LM disease at initial procedure. View this table: Table 1. Late adverse events Conclusions: Five-year clinical outcome of SES implantation for unprotected LM disease was relatively favorable and the risk of late adverse events seemed to be an acceptable range. However, the high risk patient for late adverse events, such as those with true bifurcation lesion and receiving complex stenting, seems to require close observation.

Gender difference on 5-year outcomes of EXCEL biodegradable polymer-coated sirolimus-eluting stents implantation: results from the CREATE study

Gender difference on 5-year outcomes of EXCEL biodegradable polymer-coated sirolimus-eluting stents implantation: results from the CREATE study

Sirolimus-eluting stent implantation for ostial right coronary artery lesions: five-year outcomes from the j-Cypher registry

Sirolimus-eluting stent implantation for ostial right coronary artery lesions: five-year outcomes from the j-Cypher registry

Six-year outcomes after sirolimus-eluting stent implantation for aorto-ostial lesions: comparison of right coronary artery with left main trunk

Six-year outcomes after sirolimus-eluting stent implantation for aorto-ostial lesions: comparison of right coronary artery with left main trunk

Sirolimus-eluting vs. paclitaxel-eluting stents in diabetic and non-diabetic patients with in "LIMUS"-stent restennosis, results from the ISAR DESIRE 2 trial

Background: Concern exists relating to potential attenuated efficacy of limus-eluting stents in patients with diabetes mellitus. In this respect diabetic patients with sirolimus-eluting stent (SES) failure requiring reintervention may be expected to derive particular benefit from a treatment-switch to paclitaxel-eluting stent (PES) implantation. Objective: The aim of the current report was to investigate outcomes of patients with SES restenosis randomized to treatment with repeat SES implantation (same stent strategy) or PES (switch stent strategy) according to the presence or absence of diabetes mellitus. Methods: In the setting of ISAR-DESIRE 2 trial patients with clinically significant SES restenosis were randomly assigned to receive either SES or PES. The primary end point was in-stent late lumen loss at 6-8 month follow-up angiography. Secondary endpoints were binary angiographic restenosis (diameter stenosis >50%) and target lesion revascularization (TLR), the composite of death or myocardial infarction (MI) and definite stent thrombosis at 12 months. Results: Of 450 patients enrolled, 162 (36.0%) had a diagnosis of diabetes mellitus. Late loss was comparable between SES and PES both in patients with diabetes (0.38±0.59mm vs. 0.37±0.59mm; p=0.97) and without (0.41±0.67mm vs. 0.38±0.6mm; p=0.98). Similarly binary restenosis was comparable between SES and PES in patients with diabetes (19.0% vs. 26.0%; p=0.32) or without (18.9% vs. 17.8%; p=0.98). TLR, death or MI and definite stent thrombosis were also similar in SES versus PES treatment groups regardless of diabetes status. ![Figure][1] Primary endpoint Conclusions: In cases of SES-restenosis, treatment with either repeat SES or switch to PES was associated with a comparable degree of efficacy and safety, regardless of diabetic status. [1]: pending:yes

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Optical coherence tomography analysis of strut coverage in biolimus- and sirolimus-eluting stents: 3-Month and 12-month serial follow-up

BackgroundNo randomized studies have been conducted to investigate serial changes in optical coherence tomography (OCT) analyses following implantation of biolimus-A9-eluting stents (BES) and sirolimus-eluting stents (SES). MethodsA total of 60 patients fulfilling the study criteria were randomly assigned into BES (n=30) and SES (n=30) implantation groups. Serial OCT evaluation at post-procedure, 3- and 12-month follow-up was performed in 46 patients [BES (n=22) and SES (n=24)]. OCT analyses were compared according to the type of stents and the follow-up time intervals. The percentage of uncovered struts was defined as the ratio of uncovered struts to total struts in all cross-sections. The primary endpoint was the percentage change (Δ) of uncovered struts in the 3- and 12-month follow-up samples. ResultsThe percentage of uncovered struts at the 3-month time period was not significantly different in the BES and SES groups; the median value (interquartile range) was 14.7% (0.0–23.4) versus 8.6% (0.7–21.5) (p=0.98), respectively. However, OCT at the 12-month follow-up showed a significantly lower percentage of uncovered struts [2.6% (0.8–5.6) versus 6.2% (1.7–14.7), (p=0.028), respectively] without significant difference of neointimal thickness. BES showed a greater reduction of percentage Δ of uncovered struts from 3–12months than that of SES [−17.2±14.5% versus −7.7±16.3%, respectively (p=0.043)]. ConclusionsBoth drug-eluting stents showed a high percentage of incomplete strut coverage at 3months. However, BES showed a significantly lower percentage of uncovered struts at 12months compared to that of SES. This was achieved by superior strut coverage from 3 to 12months.