Single Sirolimus-eluting Stent Research Articles

Pharmacokinetics of sirolimus-eluting stents implanted in the neonatal arterial duct.

Sirolimus-eluting stents may have clinical advantages over bare-metal stents in the extremely proliferative environment of the neonatal arterial duct. However, sirolimus has immunosuppressive actions and little is known regarding sirolimus pharmacokinetics in the newborn. This is a retrospective review of sirolimus pharmacokinetics in neonates who underwent sirolimus-eluting stent implantation in the arterial duct for pulmonary blood flow augmentation. Pharmacokinetic parameters were obtained by noncompartmental analysis and by a Bayesian one-compartment nonlinear mixed model. Nine neonates received a single sirolimus-eluting stent with a total sirolimus dose of 245 μg (n = 1), 194 μg (n = 5), or 143 μg (n = 3). Peak sirolimus concentrations were 13.6 ± 4.5 μg/L (24.8 μg/L highest) and clearance was 0.042 ± 0.03 L/hour (noncompartmental analysis) and 0.051 L/hour (95% credible intervals 0.037-0.069, nonlinear mixed model). Sirolimus remained > 5 μg/L, the trough level used in oral immunosuppressive therapy, for (95% credible interval) 15.9 (11.4, 22.8), 12.9 (7.6, 19.0), and 8.4 (2.3, 14.5) days for the 245, 194, and 143 μg sirolimus dose stents, respectively. Estimates of the duration of systemic immunosuppression are provided for combinations of 2 stents. In neonates after sirolimus-eluting stent implantation, peak sirolimus levels were 20 × higher and clearance 30 × lower than previously reported in older children and adults. Sirolimus levels were within the immunosuppressive range for a prolonged period, but with no observable clinically significant adverse outcomes.

Clinical outcomes in low risk coronary artery disease patients treated with different limus-based drug-eluting stents--a nationwide retrospective cohort study using insurance claims database.

The clinical outcomes of different limus-based drug-eluting stents (DES) in a real-world setting have not been well defined. The aim of this study was to investigate the clinical outcomes of three different limus-based DES, namely sirolimus-eluting stent (SES), Endeavor zotarolimus-eluting stent (E-ZES) and everolimus-eluting stent (EES), using a national insurance claims database. We identified all patients who received implantation of single SES, E-ZES or EES between January 1, 2007 and December 31, 2009 from the National Health Insurance claims database, Taiwan. Follow-up was through December 31, 2011 for all selected clinical outcomes. The primary end-point was all-cause mortality. Secondary end-points included acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. Cox regression model adjusting for baseline characteristics was used to compare the relative risks of different outcomes among the three different limus-based DES. Totally, 6584 patients were evaluated (n=2142 for SES, n=3445 for E-ZES, and n=997 for EES). After adjusting for baseline characteristics, we found no statistically significant difference in the risk of all-cause mortality in three DES groups (adjusted hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 0.94-1.38, p=0.20 in E-ZES group compared with SES group; adjusted HR: 0.77, 95% CI: 0.54-1.10, p=0.15 in EES group compared with SES group). Similarly, we found no difference in the three stent groups in risks of acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. In conclusion, we observed no difference in all-cause mortality, acute coronary events, heart failure needing hospitalization, and cerebrovascular disease in patients treated with SES, E-ZES, and EES in a real-world population-based setting in Taiwan.

Very late stent thrombosis after sirolimus-eluting stent implantation: evaluation by intravascular ultrasound and optical coherence tomography

A 58-year-old man was admitted to our hospital with acute anterior myocardial infarction that occurred 4 years after single sirolimus-eluting stent (SES) implantation in the left anterior descending artery. He had been undergoing continuous dual antiplatelet therapy. Emergency coronary angiography showed total thrombotic occlusion and peri-stent contrast staining at the SES site. The lesion was evaluated using intravascular ultrasound (IVUS) and optical coherence tomography (OCT) after thrombectomy. Vessel remodeling was detected on IVUS, and multiple interstrut hollows and thrombi were observed on OCT. These findings were associated with very late stent thrombosis after SES implantation.

Abstract 9910: Chronic Inflammatory Responses to Polymer Can Evoke Both Late Restenosis and Very Late Stent Thrombosis After Sirolimus-Eluting Stent Implantation in Human Coronary Arteries

Background: Sirolimus-eluting stents (SES) can reduce the rate of restenosis by marked inhibition of neointimal hyperplasia. However, late adverse events occurring more than 1 year (Y) after SES implantation, in-stent late luminal loss (LLL) and very late stent thrombosis (VLST), have been reported. The detailed mechanisms of these events are poorly understood at present. Methods and Results: Postmortem histopathological investigation of late vascular responses of coronary arteries was performed in 32 consecutive patients (pts) more than 1 Y after SES implantation. Although most simple lesions with a single SES showed gradual endothelial coverage (80 to 90%) after 1 Y, there was considerable inflammatory reaction involving T lymphocytes (T cells), macrophages (MΦ) and multinucleated giant cells adjacent to the struts. Furthermore, 14 cases showed necrotic core formation with numerous circumferential cholesterol clefts and pronounced infiltration by lipid-laden MΦ that were immunoreactive for collagen-degrading matrix metalloproteinases around the struts. In 3 of these arteries, the luminal surface was focally ruptured and massive thrombi composed of platelets and fibrin were observed. Furthermore, in 2 pts who died of VLST more than 2 Y after SES implantation, the arterial wall of SES segments was aneurysmally dilated with an extensive inflammatory infiltrate involving the intima, media and adventitia consisting predominantly of T cells and eosinophils, and occasional giant cells. Furthermore, 2 other pts developing coronary aneurysms in the stented segments demonstrated diffuse restenosis. Granulomatous inflammatory reaction with mild to moderate inflammatory cell infiltration but remarkable smooth muscle cell proliferation was clearly observed in the restenotic regions in these pts. Conclusions: These findings suggest that the polymer of SES can evoke significant chronic destructive and/or proliferative inflammatory responses followed by severe adverse clinical events such as LLL or VLST, depending on the intensity of inflammation. Although relatively milder inflammatory changes induce intimal hyperplasia, vessel wall destruction by severe inflammation can lead to aneurysm formation in extreme cases.

Angiographic late lumen loss at the site of overlap of multiple Cypher™ sirolimus-eluting stents: ALSOCE study

It has been reported that the overlap of sirolimus-eluting stents (SESs) is associated with greater in-stent late lumen loss and more angiographic restenosis. The purpose of this study was to evaluate whether the site of such overlap shows increased or decreased late lumen loss as assessed by quantitative coronary angiogram. We compared 7-month angiographic late lumen loss at the site of overlap in patients with multiple overlapping stents (overlap SES group, n=48) to that in patients with single stents (single SES group, n=144). With regard to baseline angiographic characteristics and procedural results, there were significant differences between the overlap SES group and the single SES group in lesion complexity, lesion length and reference diameter, minimal lumen diameter, and mean stent length. In-stent late lumen loss at the 7-month follow-up did not differ significantly between the two groups (overlap SES 0.25 ± 0.61 mm vs. single SES 0.10 ± 0.55 mm, p=0.11). Furthermore, the site of overlap in the overlap SES group did not show greater late lumen loss compared to the stented area in the single SES group (0.17 ± 0.55 mm vs. 0.10 ± 0.55 mm, p=0.43). The overlap SES group tended to be associated with an increase in binary restenosis compared with the single SES group (22.8% vs. 12.8%, p=0.08), while this value was 4.2% at the site of overlap. There were no significant differences in death, myocardial infarction, target lesion revascularization, or stent thrombosis between the two groups. In addition, stent length was the most independent factor of late lumen loss in the overlap SES group by multivariate logistic analysis, whereas it was not an independent factor of late lumen loss of the SES overlap segment. The site of overlap of overlapping SES dose not associate with greater late lumen loss or a higher in-stent binary restenosis rate compared to single SES implantation. The overlapping of SES by itself did not increase in-stent late lumen loss.

Moderate stenosis in left main trunk side branches treated with single sirolimus-eluting stents should be observed without additional stenting

The sirolimus-eluting stent (SES) has dramatically reduced restenosis in patients with most types of coronary lesions, but bifurcation lesions remain a predictor of poor prognosis even in SES implantation. We aimed to determine the clinical outcomes of the left main trunk (LMT) side branches (SB) treated with a single SES strategy. SES implantation was successfully performed on 70 patients with LMT stenosis from August 2005 to August 2008. Of the 70 patients, 55 patients (59 SB) were treated with a single SES and a jailed SB. The 56 SB were divided into two groups according to percent diameter stenosis immediately following percutaneous coronary intervention (PCI) (Group 1: >50%; Group 2: <50%). Quantitative coronary angiography (QCA) data was evaluated. One year angiographic follow-up was performed on 23 patients (82.1%) in Group 1, and 21 patients (78.6%) in Group 2. Group 1 MLD was significantly larger at follow up than that post-PCI (0.9±0.4 vs. 1.2mm±0.6mm, p<0.01). In Group 2, MLD and percent diameter stenosis did not change significantly. SB revascularization was not performed on either group at follow-up. Clinical outcomes of moderate stenosis in LMT SB treated with a single SES were acceptable, and stenosis progression within 1year was minimal. We concluded that patients who present moderate residual stenosis in LMT SB with no presentation of ischemic symptoms should be observed rather than re-stented.

Serial angiographic and intravascular ultrasound evaluation to interrogate the presence of late “catch-up” phenomenon after cypher® sirolimus-eluting stent implantation

Despite the expressive reduction in the intimal hyperplasia (IH) formation after DES implantation at the mid-term, late restenosis has been recently noticed. Our objective was to determine, by means of serial angiography (QCA) and intravascular ultrasound (IVUS) at two different time points, whether the occurrence of the "late catch-up" phenomenon occurs after sirolimus-eluting stent (SES) implantation. Thirty-eight non-complex patients treated with a single 18-mm SES who had systematic serial QCA and IVUS analyses at mean 8 and 20months were enrolled. Primary endpoint is to evaluate the temporal course of IH formation after SES implantation, by comparing QCA in-stent late loss and IVUS percent IH obstruction between the invasive follow-ups. Mean cohort age was 59.3years and 31.6% were diabetics. Baseline reference vessel diameter was 2.8 ± 0.4mm and lesion length was 11.5 ± 3.5mm. Left anterior descending artery was the most frequent target vessel (55.3%). Between 8 and 20months, a non-significant increase in in-stent late loss from 0.10 ± 0.18 to 0.15 ± 0.30mm (P=0.38) was observed. By IVUS, a slight increase in the percent IH obstruction (1.03 ± 2.13 to 1.76 ± 1.87%, P=0.12) was detected between the two evaluations. Interestingly, all the neoformed tissue accrued from 8 to 20months accumulated in the distal portion of the stent. In the non-complex scenario, SES implantation was associated with a minimal, non-significant increase in the IH volume between 8 and 20months.

Relationship between neointimal coverage of sirolimus-eluting stents and lesion characteristics: A study with serial coronary angioscopy

Delayed neointimal coverage after the implantation of a drug-eluting stent (DES) is thought to be related to their potential for developing late-stent thrombosis. However, few studies have shown which factor affects the neointimal coverage after DES implantation. We hypothesized that the extent of neointimal coverage after DES implantation is affected by the underlying lesion characteristics because arterial wall components are reported to determine the transport and distribution of the drugs. Thirty-seven coronary artery lesions treated with a single sirolimus-eluting stent (SES) were evaluated in 37 patients with stable coronary artery disease. Angioscopy was performed before, immediately after, and 6 months after stenting to examine the existence of yellow plaque, thrombus, complex plaque, and intramural hemorrhage and the degree of neointimal coverage at 6-month follow-up. This was classified either as a noncoverage group (stent struts were predominantly exposed or visible through a thin neointima) or as a coverage group (stent struts were predominantly covered by neointimal hyperplasia and thus invisible). Twenty-one lesions were classified into the noncoverage group, and 16 lesions the coverage group. The frequency of preexistent yellow plaques was significantly higher in the noncoverage group than that in the coverage group (67% vs 19%, P = .007). A multivariate logistic regression analysis showed the preexistence of yellow plaque was the only independent factor behind less neointimal coverage at 6 months after SES implantation (odds ratio 19.5, 95% confidence interval 1.58-240.50, P = .020). The preexistence of yellow plaque may be associated with decreased neointimal coverage of SES.

Impact of a prolonged delivery inflation time for optimal drug‐eluting stent expansion

We examined the importance of prolonged inflation time for optimal sirolimus-eluting stent (SES) or paclitaxel-eluting stent (PES) expansion. Eighty-one de novo lesions deployed single SES or PES between April 2007 and March 2008 were divided into four groups; group 1: 21 SES deployed at 20 atm x 60 sec, group 2: 20 SES deployed with 2-step inflation at 20 atm x 60 sec following 20 atm x 20 sec, group 3: 20 PES deployed same as group 1, group 4: 20 PES deployed same as group 2. The minimal lumen diameter (MLD) and stent expansion ratio (SER; stent cross- sectional area at lesion/balloon cross-sectional area which was calculated according to the compliance chart at the same atmosphere as stent deployment) were compared between group 1 and group 2 in SES, between group 3 and group 4 in PES. The MLD of post 60 sec was significantly higher than that of post 20 sec (2.84 +/- 0.28 mm in group 1, 2.76 +/- 0.33 mm in group 2 vs. 2.54 +/- 0.33 mm in group 2; P = 0.003, 0.045, respectively and 2.94 +/- 0.28 mm in group 3, 3.00 +/- 0.34 mm in group 4 vs. 2.69 +/- 0.35 mm in group 4; P = 0.022, 0.007, respectively). The SER of post 60 sec was significantly higher than that of post 20 sec (79.3% +/- 8.5% in group 1, 80.8% +/- 7.8% in group 2 vs. 71.1% +/- 10.2% in group 2; P = 0.014, 0.011, respectively and 81.1% +/- 7.9% in group 3, 84.3% +/- 9.9% in group 4 vs. 72.6% +/- 10.5% in group 4, P = 0.011, 0.001, respectively). The prolonged delivery inflation for 60 sec may result in a more optimal stent expansion. It is therefore considered to be a useful method for deploying drug-eluting stent.

Intravascular Ultrasound Comparison of Sirolimus-Eluting Stent Versus Bare Metal Stent Implantation in Diseased Saphenous Vein Grafts (from the RRISC [Reduction of Restenosis In Saphenous Vein Grafts With Cypher Sirolimus-Eluting Stent] Trial)

The randomized Reduction of Restenosis In Saphenous Vein Grafts with Cypher Sirolimus-Eluting Stent trial compared angiographic outcomes of sirolimus-eluting stents (SESs) versus bare metal stents (BMSs) in saphenous vein grafts (SVG). Using intravascular ultrasound (IVUS) performed during 6-month follow-up angiography, we compared the vascular effects of the 2 types of stent on SVGs. Of 75 patients (96 lesions) included, 59 patients underwent IVUS in 61 SVGs; 29 patients received 40 SESs for 34 lesions, and 30 patients received 42 BMSs for 39 lesions. IVUS parameters (diameters, areas, and volumes) were compared in the 2 groups. A specific analysis was performed for overlapping SESs. Median neointimal volume was 1.3 mm(3) (interquartile range 0 to 13.1) in SESs versus 24.5 (7.8 to 39.5) in BMSs (p <0.001). Minimal incomplete stent apposition was detected at only 3 stent edges (2 BMSs, 1 SES) next to ectatic regions of the SVG. Compared with single SESs, overlapping SESs showed significant increases in neointimal reaction, with a neointimal volume of 0.6 mm(3)/mm of stent (0.1 to 1.8) versus 0 (0 to 0.4) in single SESs (p = 0.03), and this phenomenon was mainly localized in overlapping SES segments, where neointimal volume per millimeter of stent was 1.1 mm(3)/mm (0.6 to 4.4) versus 0 (0 to 1.3) in nonoverlapping segments (p = 0.05). In conclusion, SESs effectively inhibit neointimal hyperplasia volume compared with BMSs in diseased vein grafts, without evidence of increased incomplete apposition risk. The neointimal response to overlapping SES layers seems higher than to a single SES layer.

The sirolimus-eluting coronary stent in clinical practice: impact of direct stenting versus stenting with balloon pre-dilatation.

When using bare metal stents (BMS), direct stenting (DS) has become an established method for percutaneous coronary interventions (PCI). If drug-eluting stents are used, DS is currently not recommended. We analysed the data of the German Cypher Stent Registry to evaluate current use and outcome of DS using the sirolimus-eluting stent (SES). 4,437 patients at 122 hospitals who received a single SES for one lesion and completed follow-up, were included. DS was performed in 1,727 (38.9%) of these patients. However, there was a wide range from 0% to 77.8% within the centres. The following factors were independently associated with the use of DS: degree of stenosis (per 10%) (p<0.0001), type C lesion (p<0.0001), three vessel disease (p<0.0001), age (per decade) (p<0.0001), target vessel = LAD (p=0.0029), diabetes mellitus (p=0.0222) and renal insufficiency (p=0.0260). There were no higher event rates for DS compared to predilatation from admission until the end of follow-up: death rates were 1.4% versus 1.9%, p=0.1854, TVR rates 7.9% versus 8.7%, p=0.3388 and TVR or MACCE rates 10.8% versus 12.1%, p=0.2088. This was confirmed after correction for confounding factors. In current clinical practice DS with the SES is performed within a very wide range at the different hospitals. Further predictors for the use of DS with the SES are similar to those known from BMS. DS with the SES in such selected patients seems to be safe and effective.

The randomised study of the double dose versus single dose sirolimus-eluting stent for the treatment of diabetic patients with de novo coronary lesions.

Even though sirolimus-eluting stents (SES) have been shown to significantly improve binary restenosis and target lesion revascularisation rates (TLR) compared to bare metal stents in diabetic patients, the revascularisation rate is still higher than those of non-diabetics. Whether a double dose (DD) of sirolimus on a stent would provide a greater reduction in neointimal hyperplasia compared to single dose (SD) SES in de novo coronary lesion of diabetic patients is unknown. A total of 56 patients (58 lesions) were prospectively randomised in a double blind fashion in a 1:1 ratio to SD (30 lesions) versus DD (28 lesions). Procedure success was achieved in all patients. QCA results at 6 months were comparable between groups, including the primary endpoint of in-stent late lumen loss (0.19+/-0.29 mm in SD versus 0.18+/-0.33 mm in DD, p=0.96). Furthermore, restenosis was not found inside the stent in either group. By IVUS, there was no late/acquired incomplete stent apposition at follow-up, and% neointimal volume was 2.2+/-1.8% in SD versus 1.7+/-2.0% in DD, p=0.44. At 1-year clinical follow-up, there was no significant difference between groups for major events, including TLR which occurred in 1 patient in SD versus 3 patients in DD, p=0.61. Overall, there was only 1 subacute stent thrombosis (DD arm), and no late thromboses. Double dose SES did not improve the prevention of neointimal proliferation in diabetic patients with de novo coronary lesion compare to single dose SES.

Impact of Three or More Versus a Single Sirolimus-Eluting Stent on Outcomes in Patients Who Undergo Percutaneous Coronary Intervention

This retrospective analysis compared clinical outcomes of patients who underwent stenting with > or =3 sirolimus-eluting stents (SESs) with those who received a single SES. SES (Cypher) implantation for single vessels is proved to be effective and durable, but knowledge regarding the safety and effectiveness of multiple stenting with SESs is currently limited. In total, 929 consecutive patients who received SESs were identified; 63 received > or =3 SESs (multi group) and 866 received 1 SES (single group). The multi group had more non-Q-wave myocardial infarctions (MIs) during the index hospitalization (p = 0.02). At 30-day follow-up, death, Q-wave MI, subacute thrombosis, and major adverse cardiac events were higher in the multi group than in the single group. At 6 months, death, Q-wave MI, target lesion revascularization, and major adverse cardiac events continued to be higher in the multi group. Using multivariate analysis, > or =3 SES implantations, American College of Cardiology/American Heart Association type C lesions, and cardiogenic shock were identified as independent predictors for 6-month major adverse cardiac events. In addition, patients in the multi group had a significantly lower survival rate than patients in the single group (p <0.0001). Patients who required > or =3 SES implantations developed increased periprocedural non-Q-wave MI and worse adverse clinical outcomes at 30 days and 6 months compared with patients who required a single SES implantation. In conclusion, when patients present with multiple coronary lesions, percutaneous coronary intervention with multiple SESs should be undertaken with great caution.

Angiographic and Clinical Outcomes of a Pharmacokinetic Study of Sirolimus-Eluting Stents Lesson From Restenosis Cases

A pharmacokinetic (PK) study was conducted to evaluate sirolimus-eluting stents (SES) in Japanese people, representing the first clinical trial of the use of drug-eluting stents in Japan. The PK study was conducted in 20 patients with 30 lesions treated with sirolimus-coated BX Velocity stents. All lesions were treated with a single SES (3 x 18 mm). Angiographic follow-up was performed at 8 months after SES implantation, and the clinical outcomes were evaluated at 1 year in all cases. All procedures were successful, and all patients were discharged without any adverse cardiac events. The total restenosis rate was 10% (3 lesions) and target vessel revascularization was performed in those 3 cases (15%). Restenoses occurred at the proximal and distal stent margins. Intravascular ultrasound examination of restenosis cases revealed abundant plaque burden at the stent edges even though the luminal area was preserved. The sirolimus-eluting BX Velocity stent is safe and useful for Japanese patients with coronary artery disease. However, restenosis at proximal stent edge seems to be a problem.