Late Catch-up Research Articles

Comparison of the “Late Catch-Up” Phenomenon Between BuMA Supreme and XIENCE Stents Through Serial Optical Coherence Tomography at 1–2 Month and 2 Year Follow-Ups: A Multicenter Study

Objectives: This study was aimed at comparing the “late catch-up” phenomenon between the BuMA Supreme bioresorbable polymer sirolimus-eluting stent and the XIENCE stent through serial optical coherence tomography (OCT) at within 2 months and 2 year follow-ups. Methods: A total of 49 of 75 patients from the PIONEER-II study were enrolled in a 2 year OCT follow-up study; 44 patients with 50 lesions were included in the statistical analysis. The primary endpoints were neointimal thickness and late luminal loss (LLL) after stent implantation. Results: The stenosis diameter, and minimum in-stent or in-segment diameter, did not significantly differ between the BuMA Supreme and XIENCE arms at within 2 months and 2 year follow-ups. The strut neointimal coverage and thickness were greater in the BuMA group than the XIENCE group at the 1 and 2 month follow-ups (P = 0.044 and P = 0.010, respectively) but not at the 2 year OCT follow-up. Neither early luminal loss at the within 2 months follow-up (P = 0.849) nor LLL at the 2 year OCT follow-up (P = 0.613) showed differences between device arms. No significant differences in imaging and clinical endpoints were observed between device arms at follow-up. Conclusions: The BuMA Supreme stent’s faster re-endothelization with no “late catch-up” phenomenon has potential advantages over the XIECE stent for patients with coronary artery disease and high bleeding risk because it decreases the duration of dual antiplatelet therapy.

P269 Mid-term clinical outcomes of biodegradable polymer everolimus-eluting stents compared with durable polymer everolimus-eluting stents: a propensity-matched study

Abstract Background Introduction: Several studies have reported that durable polymer drug-eluting stents could cause delayed healing and late catch-up. Although biodegradable polymer everolimus-eluting stents (BP-EES) might solve these problems, there is few data about mid-term clinical outcomes of BP-EES compared with durable polymer everolimus-eluting stents (DP-EES). Purpose This study aimed to compare mid-term clinical outcomes between BP-EES and DP-EES. Methods Between January to December 2016, 206 consecutive patients were treated with BP-EES and 177 consecutive patients were treated with DP-EES in our Heart Center. The primary endpoint was 3-year cumulative incidence of target lesion failure (TLF) defined as cardiac death, target vessel-related myocardial infarction and clinical-driven target lesion revascularization. Moreover, clinical-driven target vessel revascularization (TVR) and definite stent thrombosis (ST) were also evaluated. Results After propensity score matching, 160 patients were selected in each group. At 3 years, the cumulative incidences of TLF were 4.1% in BP-EES group vs. 7.9% in DP-EES (p = 0.12). Similarly, those of clinical-driven TVR were not different between the 2 groups (10.9% vs. 8.0%, p = 0.39). The incidence of definite ST in BP-EES tended to be higher than in that of DP-EES (BP-EES vs. DP-EES; 0% vs. 1.8%, p = 0.06). Conclusions There were no significant differences of TLF between BP-EES and DP-EES within 3 years. In this study, BP-EES seems to prevent definite ST and be safer than DP-EES in mid-term. Abstract P269 Figure.

Early growth patterns are associated with intelligence quotient scores in children born small-for-gestational age

ObjectiveTo assess whether patterns of growth trajectory during infancy are associated with intelligence quotient (IQ) scores at 4years of age in children born small-for-gestational age (SGA). MethodsChildren in the Collaborative Perinatal Project born SGA were eligible for analysis. The primary outcome was the Stanford–Binet IQ score at 4years of age. Growth patterns were defined based on changes in weight-for-age z-scores from birth to 4months and 4 to 12months of age and consisted of steady, early catch-up, late catch-up, constant catch-up, early catch-down, late catch-down, constant catch-down, early catch-up & late catch-down, and early catch-down & late catch-up. Multivariate linear regression was used to assess associations between patterns of growth and IQ. ResultsWe evaluated patterns of growth and IQ in 5640 children. Compared with children with steady growth, IQ scores were 2.9 [standard deviation (SD)=0.54], 1.5 (SD=0.63), and 2.2 (SD=0.9) higher in children with early catch-up, early catch-up and later catch-down, and constant catch-up growth patterns, respectively, and 4.4 (SD=1.4) and 3.9 (SD=1.5) lower in children with early catch-down & late catch-up, and early catch-down growth patterns, respectively. ConclusionsPatterns in weight gain before 4months of age were associated with differences in IQ scores at 4years of age, with children with early catch-up having slightly higher IQ scores than children with steady growth and children with early catch-down having slightly lower IQ scores. These findings have implications for early infant nutrition in children born SGA.

0387 : Incidence and predictors of the late catch-up phenomenon after drug-eluting stent implantation

Although clinical restenosis within 1year after percutaneous coronary intervention has been remarkably reduced with the advent of drugeluting stents (DES), the late catch-up (LCU) phenomenon remains an issue despite medical advances. The aim of this study was to investigate the incidence and predictive factors of the LCU phenomenon in an unselected population treated with DES. A total of 936 lesions treated with DES between June 2002 and June 2010 were analyzed. The LCU phenomenon was defined as secondary revascularization 1 year after index stenting. Incidence of the LCU phenomenon was seen in 103 lesions (11,04%). In the multivariate analysis, severe calcifications [odds ratio (OR) 6.07, p=0.017], restenosis lesion (OR 1.58, p=0.003), and long lesions (OR 2.06, p=0.031) were identified as independent predictors of the LCU phenomenon. The LCU phenomenon is associated with serious consequences and adverse events and remains an important issue in modern practice, despite medical advances. Special consideration must be given to patients with restenosis lesion, long lesions and severe calcifications.

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.

Coronary Stent Evolution – From Pathology to Clinic

Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. The pathogenesis of CAD relates to the presence of atherosclerotic plaques in coronary arteries, which are today most frequently treated by percutaneous coronary intervention. Initially, plain old balloon angioplasty demonstrated feasibility of dilating atherosclerotic coronary lesions; however, the high rate of acute-vessel recoil, restenosis, and dissection resulted in high acute closure rates and restenosis, which lead to the introduction of coronary stents, improving clinical outcome. However, in-stent restenosis (ISR) became the Achilles heel of bare metal stents owing to sustained neointimal (NI) growth. Drug-eluting stents (DES) were developed to reduce ISR, improving clinical outcomes and reducing the need for target vessel revascularisation. However, late and very late stent thrombosis emerged as a new problem compromising long-term results of DES, along with late catch-up of NI growth. Better materials, especially more biocompatible polymers, contributed to the refinement of DES technology, which substantially reduced stent thrombosis rates in second-generation DES. The idea of eliminating the foreign material after temporary scaffolding using fully bioresorbable scaffolds may hold great potential to revisit the interventional approach of treating CAD. This article will review the evolution of coronary artery intervention from clinical application to pathology, and will discuss current status and potential future directions of the newer therapeutic approaches.

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.

5-Year Results of a Randomized Comparison of XIENCE V Everolimus-Eluting and TAXUS Paclitaxel-Eluting Stents: Final Results From the SPIRIT III Trial (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions)

This study sought to evaluate the long-term safety and efficacy of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in patients with obstructive coronary artery disease. The use of EES compared to PES has been shown to result in improved clinical outcomes in patients undergoing PCI. However, there have been concerns regarding the durability of these benefits over longer-term follow-up. SPIRIT III was a prospective, multicenter trial in which 1,002 patients were randomized 2:1 to EES versus PES. Endpoints included ischemia-driven target vessel failure (TVF) (death, myocardial infarction (MI), or ischemia-driven target vessel revascularization [TVR]), the pre-specified primary endpoint), target lesion failure (TLF) (cardiac death, target-vessel MI, or ischemia-driven target lesion revascularization [TLR]), major adverse cardiac events (MACE) (cardiac death, MI, or ischemia-driven TLR), their individual components and stent thrombosis. Five-year follow-up was available in 91.9% of patients. Treatment with EES versus PES resulted in lower 5-year Kaplan-Meier rates of TVF (19.3% vs. 24.5%, p = 0.05), TLF (12.7% vs. 19.0%, p= 0.008), and MACE (13.2% vs. 20.7%, p = 0.007). EES also resulted in reduced rates of all-cause death (5.9% vs. 10.1%, p = 0.02), with nonsignificantly different rates of MI, stent thrombosis, and TLR, and no evidence of late catch-up of TLR over time. At 5 years after treatment, EES compared to PES resulted in durable benefits in composite safety and efficacy measures as well as all-cause mortality. Additionally, the absolute difference in TLR between devices remained stable over time without deterioration of effect during late follow-up.

TCT-184 Late Adverse Events After Implantation of Sirolimus-eluting Stent and Bare-metal Stent: 4-7 years follow-up of the CREDO-Kyoto Registry Cohort-2

Background: Late adverse events such as very late stent thrombosis (VLST) or late target-lesion revascularization (TLR) have emerged as new problems after drugeluting stent implantation. However, there is a paucity of data from long-term followup studies evaluating late adverse events after sirolimus-eluting stents (SES) implantation in comparison with bare-metal stent (BMS) implantation. Methods: Among 13058 consecutive patients undergoing first percutaneous coronary intervention in the CREDO-Kyoto registry Cohort-2, 5078 patients were treated with SES only and 5392 patients were treated with BMS only. Median follow-up duration was 1974 (inter-quartile range: 1700-2225) days. Results: During 4-7 years follow-up after SES implantation, VLST and late TLR beyond 1-year occurred constantly and without attenuation at 0.24%/year, and 2.0%/ year, respectively. Cumulative 7-year incidence of VLST was significantly higher in the SES group than in the BMS group (1.43% vs. 0.68%, P<0.0001). However, there was no excess of all-cause death beyond 1-year in the SES group as compared with the BMS group (20.8% vs. 19.6%, P1⁄40.91), although the cumulative incidence of sudden death beyond 1-year was slightly but significantly higher in the SES group than in the BMS group (3.0% vs. 1.8%, P1⁄40.02). Cumulative 7-year incidences of late TLR and clinically-driven late TLR were also significantly higher in the SES group than in the BMS group (12.0% vs. 4.1%, P<0.0001 and 8.5% vs. 2.6%, P<0.0001, respectively), leading to significant late catch-up of the SES group to the BMS group regarding the cumulative incidence of over-all and clinically-driven TLR through 7-year (18.8% vs. 25.2%, and 10.6% vs. 10.2%, respectively). Clinical indication of late TLR in the SES group included acute myocardial infarction (13.1%), unstable angina (8.1%), stable angina (34.0%), asymptomatic ischemia (7.9%) and non-clinically driven (36.9%). Conclusions: During 4-7 years follow-up after SES implantation, late adverse events including VLST and late TLR continued to occur without attenuation of their incidences. Late catch-up phenomenon of SES relative to BMS in terms of TLR was real and should be the target for the development of drug-eluting stents.

Late catch-up in lumen diameter at five-year angiography in MACE-free patients treated with sirolimus-eluting stents in the Primary Stenting of Totally Occluded Native Coronary Arteries: a randomised comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions (PRISON II)

The present study was designed to examine the five-year angiographic follow-up of MACE-free patients enrolled in the PRISON II study. In the PRISON II study a total of 200 patients were randomised to either bare metal stents (BMS) or sirolimus-eluting stents (SES) after successful recanalisation of total coronary occlusions (TCO). Patients free of MACE with available angiography at six months were approached for repeated angiography at five years. The primary endpoint was in-stent very late luminal loss (VLLL) at five years. The secondary endpoint was additional late luminal loss (ALLL) between six months and five years. At five years, repeated angiography was performed in 72 patients, 50/82 (61%) in the SES group and 22/58 (38%) in the BMS group. In-stent VLLL was lower in the SES group (0.19 mm ± 0.72 vs. 0.51 mm ± 0.71, p=0.09) compared to the BMS group and in-segment VLLL was comparable in both groups (0.01 mm±0.58 vs. 0.03 mm ± 0.73, p=0.89). Late catch-up in lumen diameter was observed in the SES group with a trend towards increased ALLL compared to the BMS group (in-stent, 0.35 mm ± 0.88 vs. 0.04 mm ± 0.81, p=0.16; in-segment, 0.20 mm ± 0.74 vs. -0.05 mm ± 0.73, p=0.19). At five-year angiographic follow-up, late catch-up was observed after successful recanalisation of TCOs treated with SES. Despite a late catch-up, the angiographic results of SES were superior in-stent and similar in-segment compared to BMS.

Incidence and predictors of the late catch-up phenomenon after drug-eluting stent implantation

Although clinical restenosis within 1 year after percutaneous coronary intervention has been remarkably reduced with the advent of drug-eluting stents (DES), the late catch-up (LCU) phenomenon remains an issue despite medical advances. The aim of this study was to investigate the incidence and predictive factors of the LCU phenomenon in an unselected population treated with first-generation DES. A total of 923 patients treated with DES between June 2004 and August 2008 were analyzed. The LCU phenomenon was defined as secondary revascularization 1 year after index stenting. Retreatment for very late stent thrombosis was considered as part of the LCU phenomenon. Incidence of the LCU phenomenon was seen in 33 patients (3.6%). Very late stent thrombosis was observed in 5 patients (0.6%) and very late in-stent restenosis was observed in 28 patients (3.0%). At the 12-month landmark analysis, the cumulative rate of cardiac death was significantly higher in patients with the LCU phenomenon than in those without any target lesion revascularization (9.0% vs. 0.9%, p<0.001). In the multivariate analysis, hemodialysis [odds ratio (OR) 6.07, p=0.003], number of stents (OR 1.58, p=0.02), and coronary bifurcation lesions (OR 2.06, p=0.048) were identified as independent predictors of the LCU phenomenon. The LCU phenomenon is associated with serious consequences and adverse events and remains an important issue in modern practice, despite medical advances. DES should be deployed with a minimum number of stents, and special consideration must be given to patients on hemodialysis and those with coronary bifurcation lesions.

Long-term serial angiographic outcomes after sirolimus-eluting stent implantation

We evaluated, using quantitative coronary angiography, the natural history of change that occurred in target lesions after successful sirolimus-eluting stent (SES) implantation. Percutaneous coronary intervention with drug-eluting stents (DES) has significantly reduced the rate of repeated target lesion revascularization. However, early studies have raised concerns regarding the "late catch-up" phenomenon of DES. Between June 2004 and March 2007, consecutive 217 patients with 306 lesions without restenosis at early angiographic follow-up underwent late angiographic follow-up (early follow-up: 11.2 ± 2.1 months and late follow-up: 29.4 ± 5.2 months). Predictors of late catch-up were identified with univariate and multivariate regression analyses. Although reference vessel diameter did not significantly change during follow-up [3.15 mm (interquartile range (IQR): 2.81-3.49 mm), 3.12 mm (IQR: 2.79-3.47 mm), and 3.08 mm (IQR: 2.76-3.46 mm) at postprocedure, and early and late angiographic follow-up, respectively; P = 0.2653], late loss (LL) significantly increased during follow-up [0.05 mm (IQR: 0.00-0.13 mm) and 0.08 mm (IQR: 0.01-0.19 mm) at early and late follow-up, respectively; P < 0.0001]. Univariate analysis showed previous intervention, adjunctive use of cutting balloon, lesion length, and progression of MLD, LL, %DS at early follow-up as predictors of late catch-up. Multivariate regression analysis identified %DS at early follow-up as a predictor of late catch-up (OR 1.076, CI 1.039-1.114, P < 0.0001). Significant and continuous progression of neointima after SES implantation was observed in the present study. Larger LL may be a sign of late catch-up phenomenon.

Comparison of 5-Year Clinical Outcomes Between Sirolimus-Versus Paclitaxel-Eluting Stent

The paclitaxel-eluting stent (PES) and sirolimus-eluting stent (SES) are first-generation drug-eluting stents (DES) that have been the most widely used; however, it is unclear whether there are differences in the long-term safety and efficacy between the 2 stents. The long-term effectiveness of DES in unselected people with diabetes is also currently unclear. Moreover, the possibility of late catch-up is suggested in the DES population. This study is an 8-center collaborative network analysis of all comers who received SES and PES. All patients who received SES and PES from February 2003 to October 2006 were enrolled. We analyzed 9315 patients (33.3% with diabetes) treated with SES or PES in the major 8 centers representing whole area of Korea. The primary end point was a major adverse cardiac event (MACE) composite of overall death, myocardial infarction, and target lesion revascularization. All analyses were performed using multivariable, adjusted models and propensity score-matching methods. Long-term MACE for 5 years were significantly lower in the SES than the PES group (13.3% versus 15.6%; hazard ratio, 0.82; 95% confidence interval, 0.71 to 0.96; P=0.01), which was mainly driven by the difference of MACE within the first year (hazard ratio, 0.73; 95% CI, 0.59 to 0.90; P=0.003), but the rate of MACE between 1 and 5 years in the landmark analysis was not different between the 2 stents (1.9 versus 2.0%/yr). In the subpopulation of people with diabetes, in contrast to the whole population, PES was comparable to SES in terms of any clinical outcome, both within the first year and from 1 to 5 years (MACE for 5 years, 20.3 versus 17.9%; MACE within the first year, 9.6 versus 8.2%; MACE 1 to 5 years, 2.9 versus 2.6%/yr). The PES was inferior to the SES in the clinical follow-up of more than 9000 patients' cohort for 5 years, which was mainly driven by the difference in the first year. In the subpopulation of people with diabetes that showed higher MACE than people without diabetes, however, PES was comparable to SES in any clinical outcome for 5 years. Although these 2 stents are not frequently used as before, the data would be useful to expect the long-term clinical course of the current DES.

Long-Term (Three-Year) Safety and Efficacy of Everolimus-Eluting Stents Compared to Paclitaxel-Eluting Stents (from the SPIRIT III Trial)

The safety and efficacy of the XIENCE V everolimus-eluting stent (EES) compared to the Taxus Express(2) paclitaxel-eluting stent (PES) has been demonstrated through 2 years in the SPIRIT II and III randomized clinical trials, but limited longer-term data have been reported. In the SPIRIT III trial, 1,002 patients with up to 2 lesions in 2 coronary arteries were randomized 2:1 to EESs versus PESs at 65 United States sites. At completion of 3-year follow-up, treatment with EES compared to PES resulted in a significant 30% decrease in the primary clinical end point of target vessel failure (cardiac death, myocardial infarction, or ischemic-driven target vessel revascularization, 13.5% vs 19.2%, hazard ratio 0.70, 95% confidence interval 0.50 to 0.96, p = 0.03) and a 43% decrease in major adverse cardiovascular events, cardiac death, myocardial infarction, or ischemic-driven target lesion revascularization (9.1% vs 15.7%, hazard ratio 0.57, 95% confidence interval 0.39 to 0.83, p = 0.003). In a landmark analysis, major adverse cardiovascular events were decreased to a similar extent with EES compared to PES 0 through 1 year and 1 year through 3 years (hazard ratio 0.56, 95% confidence interval 0.35 to 0.90; hazard ratio 0.59, 95% confidence interval 0.31 to 1.11, respectively). In conclusion, patients treated with EES rather than PES in the SPIRIT III trial had significantly improved event-free survival at 3 years. From 1 year to 3 years hazard curves continued to diverge in favor of EES, consistent with an improving long-term safety and efficacy profile of EES compared to PES, with no evidence of late catchup.

The influence of intensive physical training on growth and pubertal development in athletes

Genetic potential for growth can be fully expressed only under favorable environmental conditions. Although moderate physical activity has beneficial effects on growth, excessive physical training may negatively affect it. Sports favoring restricted energy availability, in the presence of high energy expenditure, are of particular concern. In gymnastics, a different pattern in skeletal maturation and linear growth was observed, resulting in an attenuation of growth potential in artistic gymnasts (AG), more pronounced in males than in females. In female rhythmic gymnasts (RG), the genetic predisposition to growth was preserved owing to a late catchup growth phenomenon. In all other sports not requiring strict dietary restrictions, no deterioration of growth has been documented so far. Intensive physical training and negative energy balance alter the hypothalamic pituitary set point at puberty, prolong the prepubertal stage, and delay pubertal development and menarche in a variety of sports. In elite RG and AG, prepubertal stage is prolonged and pubertal development is entirely shifted to a later age, following the bone maturation rather than the chronological age.

1-Year Results of the Hydroxyapatite Polymer-Free Sirolimus-Eluting Stent for the Treatment of Single De Novo Coronary Lesions: The VESTASYNC I Trial

We sought to assess the safety and efficacy of the novel VESTAsync-eluting stent (MIV Therapeutics, Atlanta, Georgia) combining a stainless steel platform with a nanothin-microporous hydroxyapatite surface coating impregnated with a polymer-free low-dose of sirolimus (55 microg). Durable polymers in first-generation drug-eluting stents (DES) have been linked to local inflammatory reaction leading to a positive vessel remodeling, late incomplete stent apposition, and in some cases, stent thrombosis. The removal of the polymer from the DES system could increase the safety profile of this novel technology. A total of 15 patients with single de novo lesions in native coronary arteries with 3.0- to 3.5-mm diameter and <or=14-mm length were enrolled in this first-in-man study. Primary end point was in-stent late lumen loss (LL) at 4 and 9 months. Baseline characteristics included mean age of 63 years and 33% of diabetics. Reference vessel diameter and lesion length were 2.7 +/- 0.3 mm and 10 +/- 2.0 mm, respectively. Procedure success was obtained in all cases. Lifelong aspirin and 5-month clopidogrel treatment were prescribed to all patients. At 4 months, in-stent LL and percentage of neointimal hyperplasia were 0.3 +/- 0.25 mm and 2.6 +/- 2.2%, respectively, with a nonsignificant increase at 9 months (0.36 +/- 0.23 mm and 4.0 +/- 2.2%, respectively). Serial intravascular ultrasound did not show late incomplete stent apposition. There were no major adverse cardiac events within 1 year of follow-up. The novel VESTAsync-eluting stent was effective in reducing LL and neointimal hyperplasia at 4 and 9 months, with no evidence of late catch-up by quantitative coronary angiography or intravascular ultrasound.

Abstract 2150: A European and Canadian Multicenter Randomized, Double-Blind Trial of the Sirolimus-Eluting Stent (SES) in Patients with De Novo Native Coronary Artery Lesions (NEW-SIRIUS): 5-Year Clinical Outcomes

Background : NEW-SIRIUS is the pooled analysis of the E-SIRIUS (n=352) and C-SIRIUS (n=100) studies, respectively, performed in Europe and Canada. Identical in design, these are multicenter randomized, double-blind trials examining the safety and efficacy of the sirolimus-eluting stent (SES) vs. an identical bare-metal stent (BMS) in 452 patients to treat de novo native long lesions in small coronary arteries, with adjunctive clopidogrel for only 2 months. Methods : The primary endpoint was in-stent minimum lumen diameter (MLD) at 8-month follow-up. Among the secondary endpoints were major adverse cardiac events(MACE) at 1, 6, 9 and 12 months, and annually up to 5 years post-procedure, as well as target lesion revascularization (TLR), target vessel revascularization (TVR) and protocol-defined stent thrombosis. Results : At 8 months, the MLD was 2.27±0.47mm in the SES vs. 1.36±0.66 mm in the BMS (p &lt; 0.001). The binary in-lesion restenosis rate was 5.1% in the SES vs. 44.2% in the BMS (p &lt; 0.001). At 4 years, there was a significantly lower incidence of MACE (SES: 15.1% vs BMS: 33.9%, p &lt; 0.001), primarily driven by a significant difference in clinically-driven TLR rates (SES: 7.1% vs. BMS: 26.0%, p &lt; 0.001). A subgroup analysis in diabetic patients (45 SES, 60 BMS) demonstrated that the in-stent MLD was larger in SES than in BMS (2.20±0.47 vs 1.14±0.64 mm, p &lt; 0.001) and the binary in-lesion restenosis rate was reduced from 56.1% (BMS) to 10.0% (RRR: 82.2%, p &lt; 0.001) at 8 months. At 4 years, the freedom from MACE in diabetic patients was 80.0% in the SES vs. 61.7% in the BMS (p = 0.031), again mainly driven by an improved freedom from clinically driven-TLR (SES: 90.8% vs. BMS: 66.9%, p=0.005), with no evidence of a late catch-up effect. Conclusion : Up to 4 years, SES were superior to BMS in the total cohort as well as in the diabetic subgroup without evidence of a late catch-up. Five-year follow-up data, including antiplatelet therapies utilization and a diabetic subgroup analyses will be available by July 2007 and presented.

Drug-Eluting Stent Update 2007

Restenosis has been called the Achilles heel of coronary stenting and is caused by a combination of factors, including neointimal proliferation, elastic recoil, reorganization of thrombus, remodeling, and inflammation.1 Long-term follow-up (>6 years) in patients with bare metal stents (BMS) shows that tissue proliferation reaches its peak at around 6 to 12 months and then regresses.2 This pattern fits with the observed increase in revascularization rates up to 1 year, after which a plateau occurs. After drug-eluting stent (DES) implantation, Carter et al3 showed a late catch-up of restenosis in sirolimus-eluting stents (SES) in porcine models. Although a 50% reduction of restenosis was observed at 30 days, restenosis rates for SES and BMS were equivalent at 6 months.3 A similar catch-up phenomenon was observed after implantation of paclitaxel-eluting stents (PES) and tacrolimus-eluting stents in porcine models.4,5 Conversely, in humans, there does not seem to be reason for concern about late catch-up for up to 4 years on both clinical and angiographic end points.6–10 However, several long-term DES studies showed that, in contrast to BMS, the neointima continued to grow up to 2 years as assessed by intravascular ultrasound.11 The discrepancy between porcine and clinical data is influenced by the temporal differences in arterial response in humans compared with animal models but also may be due to differences in species response to sirolimus and paclitaxel and physiological stimuli for neointimal formation. ### The Problem of Restenosis Restenosis has always been considered a benign and harmless entity. However, recent studies assessing the clinical presentation and long-term outcome of patients presenting with in-stent restenosis demonstrated worrying findings, leading some critics to ask whether restenosis had simply been traded for long-term issues like thrombosis and mortality.12 At least 10% of all cases of BMS in-stent restenosis presented with a myocardial infarction …

Late intravascular ultrasound findings of patients treated with brachytherapy for diffuse in-stent restenosis.

This study aimed at evaluating long-term (24-month) effects of beta-irradiation (188Re-MAG3-filled balloon) using intravascular ultrasound (IVUS) in patients with in-stent restenosis (ISR). Long-term effects of beta-irradiation on intimal hyperplasia (IH) within the stented segment and vessel and lumen dimensions of nonstented adjacent segments in patients with ISR have not been sufficiently evaluated. Two-year follow-up IVUS was performed in 30 patients with patent ISR segments at 6-month follow-up angiography. Serial IVUS images were acquired at five equidistant intrastent sites and at three different reference segment sites. IH burden (%) was defined as 100 x (IH/stent area). Mean intrastent IH area and IH burden significantly increased between 6 and 24 months, from 2.1 +/- 1.1 to 2.6 +/- 1.4 mm2 (P < 0.001) and from 26% +/- 10% to 33% +/- 14% (P < 0.001), respectively. There was a significant decrease of mean external elastic membrane (from 10.1 +/- 3.9 to 9.7 +/- 3.9 mm2; P = 0.015) and lumen area (from 5.6 +/- 2.3 to 5.1 +/- 2.3 mm2; P = 0.021) within distal reference segments between 6 and 24 months. Target lesion revascularization (TLR) was performed in six patients (20%) between 6 and 24 months after beta-irradiation therapy. There were no significant differences between TLR and non-TLR groups except for a smaller minimum lumen area at 24 months in the TLR group. Because of a small amount of late loss between 6 and 24 months, most irradiated ISR vessel segments remained stable for up to 2 years. However, quantitative evidence of late catch-up was evident in most patients and was significantly associated with 24-month TLR in some patients.

New frontiers in cardiology: drug-eluting stents: Part II.

In this second part of the article, we will complete the review of drug-eluting stent technologies (Table 1) and discuss methodological and technical aspects of drug-eluting stents. View this table: TABLE 1. Drug-Eluting Stent Platforms Under Investigation ### Biological Agents (Continued) #### (1) Stents Eluting Antiproliferative Agents A number of antineoplastic medications have been considered for the prevention of restenosis. Paclitaxel and its derivatives have been the most investigated compounds of this group. ##### (a) Paclitaxel-Eluting Stents Paclitaxel (Taxol; Bristol-Myers Squibb) is a microtubule-stabilizing agent with potent antitumor activity.1 Many different platforms that use polymer coating or surface modifications to adhere paclitaxel onto the stents have been utilized over the past 2 years. ###### Preclinical Data Unlike other antimitotic agents, paclitaxel shifts the cytoskeleton equilibrium toward assembly, leading to reduced vascular cell proliferation, migration, and signal transduction.2 Paclitaxel is highly lipophilic, resulting in a rapid cellular uptake and a long-lasting effect in the cell.3 NIR stents (Boston Scientific Corp) coated with poly(lactide-co-Σ-caprolactone) copolymer and paclitaxel (200 μg/stent) were placed in porcine coronary arteries. Paclitaxel-eluting stents showed a marked reduction in neointimal and medial cell proliferation at all time points (7, 28, 56, and 180 days).4 However, arteries treated with paclitaxel showed incomplete healing, late persistence of a large number of macrophages, and fibrin deposition. Similar findings were observed with a stent platform coated with cross-linked biodegradable polymer (chondroitin sulfate and gelatin) and 42.0, 20.2, 8.6, or 1.5 μg of paclitaxel in rabbit iliac arteries.5 These studies indicate the need for a more controlled drug release of paclitaxel due to the narrow toxic-therapeutic window and high hydrophobic character of this compound. ###### Clinical Data: De Novo Lesions The QuaDS drug-eluting stent (Quanam Medical Corp) was the first drug-eluting stent implanted in human coronary arteries. This slotted tube stent has 50% of its surface area covered by multiple nonbiodegradable polyacrylate sleeves that release 7-hexanoyltaxol (called QP2 or taxane). Approximately 800 μg of the …