Rate Of Late Stent Thrombosis Research Articles

Factors Influencing 1st and 2nd Generation Drug-Eluting Stent Performance: Understanding the Basic Pharmaceutical Drug-in-Polymer Formulation Factors Contributing to Stent Thrombosis Do We Really Need to Eliminate the Polymer?

Drug-eluting stents (DES) have a major role in treating cardiovascular disease. The evolution of bare metal stents into 1st generation durable-polymer DES (DP-DES) reduced the rate of in-stent restenosis (ISR) and the need for repeat-revascularization. However, clinical outcomes showed similar rates of late stent thrombosis (ST<1 year) and higher rates of very late stent thrombosis (ST>1 year) necessitating the advent of 2nd generation more biocompatible polymer DES and biodegradable-polymer DES (BP-DES) that reduced ST rates with shorter dual anti-platelet therapy (DAPT). Despite the improvements in drugs and polymer biocompatibility for both durable and biodegradable polymers, stent thrombosis remains an issue. Doubts remain about the safety and efficacy of the more biocompatible 2nd generation durable polymers in respect to vessel inflammatory and thrombogenic response as compared to biodegradable polymers despite clinical trial and meta-analyses evidence indicating that 2nd generation DP-DES are non-inferior to BP-DES for stent thrombosis. A long-term presence of the polymer can cause inflammation and thrombogenesis. However, the cause of stent thrombosis is multi-factorial from a drug-in-polymer formulation perspective; e.g., drug release kinetics, drug physiochemical and pharmacological properties, degradation kinetics; polymer biocompatibility and hemocompatibility and coating properties. It appears that the focus should be on controlling burst release and developing more biocompatible, durable polymers, especially considering the cost of PCI utilizing biodegradable, polymer-free and bioresorbable scaffolds. This may give an insight into certain DP-DES effectiveness as compared to BP-DES for the existing clinical data and improve future stent development.

OCT analysis of early endothelialization of the Synergy stent in young non-ST segment elevation acute coronary syndrome. The OCT EROS study

Early healing of the struts is a major challenge to reduce the risk of late stent thrombosis (LST), and for decreasing the duration of dual antiplatelet therapy (1 or 3 months), in patients high risk of bleeding. The bioresorbable polymer everolimus eluting stent (EES) SYNERGY, new generation of stent, has biocompatibility and mechanical properties, allowing complete strut coverage throughout the entire length of the stent at 3 months, in humans, resulting in a low rate of LST. Optical Coherence tomography analysis (OCT), which provide the best spatial resolution, is the method of choice to evaluate early healing of the strut. To estimate the early healing of the strut at 1 month after implantation of the EES, using OCT analysis, in patients admitted for acute coronary syndrome without ST segment elevation. This was a prospective and mono-centric study performed at the university hospital the North of Marseille. The patients eligible had to benefit from complementary angioplasty at 1 month after implantation of the EES for the culprit lesion of the acute coronary syndrome. An OCT of EES implanted was performed. OCT analysis and proofreading of coronary angiography were achieved by 2 physicians practicing these tests on daily basis. The primary study endpoint was the percentage of uncovered struts in OCT imaging, at 1 month ( Fig. 1 ). Twenty-four patients were included between December 2016 and February 2018. The percentage of uncovered struts was 21,48 ± 10% of 3849 struts analyzed. The neointimal thickness facing covered struts was 0,0508 ± 0,016mm. At follow-up, no ischemic event was reported, however, one death by hemorrhagic stroke was identified. The percentage of uncovered struts of the SYNERGY stent was 21,48% at 1 month post angioplasty in the context of ACS. This result provides a logical rationale for decreasing the duration of dual antiplatelet therapy at 1 month in patients at high risk of bleeding.

Early and Late Stent Thrombosis in Patients with Versus Without Diabetes Mellitus Following Percutaneous Coronary Intervention with Drug-Eluting Stents: A Systematic Review and Meta-Analysis.

Nowadays, drug-eluting stents (DES) are most commonly used compared with bare metal stents (BMS) since the former are associated with significantly lower rates of revascularization following percutaneous coronary intervention (PCI). However, unpredictable in-stent thrombosis is a major concern with DES, especially in patients with diabetes mellitus. In this analysis, we aimed to systematically compare early and late stent thrombosis in patients with versus without diabetes mellitus following PCI with DES. Studies were included if they were randomized controlled trials or observational studies comparing patients with diabetes mellitus versus those without it following PCI with DES and they reported acute and sub-acute/early and late stent thrombosis among their clinical outcomes. Early stent thrombosis was defined as stent thrombosis that occurred before 30days and late stent thrombosis was defined as stent thrombosis that occurred after 30days following PCI. The statistical analysis was carried out by the new version of the RevMan software (version 5.3), and odds ratios (ORs) and 95% confidence intervals (CIs) were considered as the statistical parameters. A total number of 18,910 patients were included in this analysis comparing early and late stent thrombosis in patients with diabetes mellitus (5123 patients) and in patients without diabetes mellitus (13,787 patients). Both groups of patients had similar rates of early stent thrombosis, with an OR of 1.30 (95% CI 0.89-1.91; P = 0.18, I2 = 9%) (4962 patients with diabetes mellitus were compared with 13,392 patients without diabetes mellitus). However, late stent thrombosis was significantly higher in patients with diabetes mellitus, with an OR of 1.95 (95% CI 1.35- 2.81; P = 0.0004, I2 = 0%) (5113 patients with diabetes mellitus and 13,775 patients without diabetes mellitus were compared). Both patients with and without diabetes mellitus had a similar rate of early stent thrombosis following PCI with DES. However, diabetes mellitus was associated with a significantly higher rate of late stent thrombosis.

A comparison of Drug Eluting Stents with different coatings in rabbit iliac artery model

Background: New generation of Drug Eluting Stents significantly reduce restenosis as compared to Bare-metal stent (BMS). At the same time, a number of clinical studies demonstrated dependence between strut endothelialization rate and rate of late stent thrombosis. Modern stent developers and manufacturers have limited number of materials for stent coating. So, it could be assumed that similar drug polymer formulation may yield similar biological effect and clinical results. Theoretically it could be assumed that similar drug polymer formulation may yield similar biological effect and clinical results and it is even possible to extrapolate clinical data from one stent model to the others (with same coating formulation). Methods and findings: We evaluated the biological response and endothelization rate of different DES with various drug-polymer formulation after implantation in rabbit iliac artery. Coating surface morphology of each stent was assessed by scanning electron microscopy (SEM) at 14 and 28-day of implantation. Conclusions: It was found that DES with similar drug-polymer formulation but different morphology demonstrated different results after implantation. At the same time, DES with different coating formulation but similar morphology demonstrated similar biological effect. Thus, our study confirms that apart from coating formulation, coating morphology and topology are critical for stent biocompatibility and endothelization rate. Our future work will be devoted to detail in vivo study of influence of the rate of polymer coating degradation on vascular healing.

Five-year clinical performance of a biodegradable polymer-coated biolimus-eluting stent in unselected patients

ObjectiveTo evaluate the long-term follow-up of the unrestricted use of a biodegradable polymer-coated drug-eluting stent in patients undergoing percutaneous coronary intervention (PCI).MethodsThe Nobori 2 study was a prospective, multicentre, observational...

Optimal interventional strategy for the treatment of coronary in-stent restenosis.

In-stent restenosis (ISR) has been an important issue in the era of percutaneous coronary intervention (PCI) since the first bare metal stent (BMS) was applied to clinical settings. BMS substantially reduces acute vessel closure and restenosis after PCI by attenuating early arterial recoil and contraction, two major limitations of plain old balloon angioplasty (POBA). Thereby, it has been considered as a major advancement over POBA. However, ISR caused by neointimal hyperplasia after stent implantation hampers the benefit of BMS by increasing the rate of target lesion revascularization (TLR) or target vessel revascularization (TVR). With the innovation of stent technology, drug-eluting stents (DES) designed to inhibit excessive neointimal growth was produced and anticipated to reduce the incidence of ISR. Indeed, the RAVEL trial (1), a double-blind randomized study comparing sirolimus-eluting stent with its non-coated counterpart, reported no restenosis in the sirolimus stent group, and 23.4% of the patient in the BMS group developed binary restenosis (P<0.001) at 6-month follow-up. Despite of these promising results, there’s still a certain proportion of ISR occurring after DES implantation due to the expansion of indications for PCI to complex coronary lesions in high-risk patients. Meanwhile, the advent of DES brought new challenges for the interventional cardiologists, such as the higher rate of late stent thrombosis and more bleeding events due to prolonged duration of dual anti-platelet therapy (DAPT). According to the type of stents previously implanted, ISR is classified as BMS ISR and DES ISR. As the literature (2,3) mentioned, 20% to 53% BMS ISR present as unstable angina and 3.5% to 20% as myocardial infarction (MI); The proportion of DES ISR manifesting as unstable angina and MI is 16% to 66% and 1% to 20% respectively. Given the clinical and prognostic importance of ISR, the debate on the optimal strategy to prevent and treat ISR is far from over.

Coronary stent selection and optimal course of dual antiplatelet therapy in patients at high bleeding or thrombotic risk: navigating between limited evidence and clinical concerns.

Optimal duration of dual antiplatelet therapy (DAPT) after coronary revascularization, in particular after drug-eluting stent (DES) implantation, is a matter of ongoing debate. First generation of DES, as compared with bare metal stents (BMS), reduce restenosis rates but increase very late stent thrombosis rates, thus requiring a prolonged course of DAPT. As a consequence, patients with high thrombotic and/or bleeding risk: have been systematically excluded from randomized trials comparing DES versus BMS; remain 'uncertain' DES candidates; should preferentially undergo BMS implantation at the time of percutaneous coronary intervention instead of DES. The Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates (ZEUS) trial is the first randomized study that demonstrated the superiority of the Zotarolimus-eluting Endeavor Sprint versus BMS in uncertain DES candidates who followed a personalized DAPT duration, which was tailored to patients's, not stent's, characteristics. The results of the ZEUS trial may support a paradigm shift in our current understanding of the most proper use of DES in practice and should trigger further research in patients at high bleeding or thrombotic risk, who have been so far largely deprived of the potential benefit provided by DES.

Stentscoronaires

The history of interventional cardiology has been marked by several technologic revolutions since the late 1970s. The first key step was the use of inflatable balloon angioplasty as an alternative to CABG surgery for coronary revascularization, followed by intracoronary delivery of bare metal stent (BMS) and drug eluting stents (DES) to drastically reduce intracoronary restenosis observed with BMS. Improved stents platforms and polymers (absorbable or biocompatible) led to a dramatic reduction in the rate of late stent thrombosis. Self-expanding stents are now available to improve stent a position especially in acute myocardial infarction. The emergence of new fully bioabsorbable stents that can be combined with antiproliferative drugs is the ongoing revolution. A new generation of stents is continuously improving and likely to become the ideal stent for coronary revascularization in the near future.

Meta‐analysis of bioabsorbable versus durable polymer drug‐eluting stents in 20,005 patients with coronary artery disease: An update

To perform an updated meta-analysis comparing biodegradable polymer drug eluting stents (BP-DES) and durable polymer drug eluting stents (DP-DES). BP-DES have been suggested to reduce late stent thrombosis (LST) rates as compared to first generation DP-DES. Recently, second generation DP-DES have replaced older DES, but comparison of these stents with BP-DES has not yielded consistent results. Medline/Web databases were searched for studies comparing BP-DES and DP-DES, and reporting rates of overall/cardiac mortality, myocardial infarction (MI), LST, target lesion revascularization (TLR) and target vessel revascularization (TVR) and late lumen loss (LLL), with a follow-up ≥6 months. Twenty studies (20,005 patients) were included in the meta-analysis. Median follow-up time was 1 year. Compared with DP-DES, BP-DES showed lower LLL (in stent: weighted mean difference WMD -0.45 mm, 95% CI -0.66 to -0.24 mm, P = 0.00001; in segment: WMD -0.15 mm, 95% CI = -0.24 to -0.06 mm, P = 0.001) and lower rates of LST (OR 0.51, 95% CI = 0.30 to 0.86, P = 0.01), although they did not improve mortality, MI, TLR, and TVR rates. BP-DES coated with sirolimus or novolimus, in comparison with biolimus or paclitaxel, were associated with reduced LLL (P < 0.0001 for subgroups). In comparison with DP-DES, BP-DES significantly reduce LLL and LST rates, without clear benefits on harder endpoints. The efficacy of BP-DES in preserving lumen patency seems larger for sirolimus and novolimus DES.

Meta-analysis of biodegradable versus durable polymer drug eluting stents in coronary artery disease: The reality?

We would like to raise a few methodological and analytical issues of the meta-analysis by Lupi et al., which showed that drug-eluting stents (DES) with biodegradable polymer significantly reduced target lesion revascularization (TLR) and late lumen loss (LLL) as compared to DES with durable polymer. This is a meta-analysis of randomized studies and we thus question the validity of the inclusion of the NOBORI Core and TIVOLI studies, which are nonrandomized trials. Secondly, the main analyses were restricted to 6–9 month angiographic data and oneyear clinical events; however, we found that the included data of the ISAR-TEST-3 study were extracted from the two-year follow-up report. This has an impact on the accuracy of the analyses of late stent thrombosis (LST) and LLL since the report gave two-year LST rates and the 6–8 month angiographic data were paired with those at two years and excluded patients who underwent TLR at 12 months. We refer the authors to the primary report of ISAR-TEST-3 study, which contains 6–8 month angiographic (including in-segment LLL) and one-year clinical data. The authors stated that 11 trials were excluded. However, there are 12 reasons of exclusion in Figure 1 and 12 excluded studies are listed in Table 2. We would like to highlight that the number of included studies should be eight (ISAR-TEST 3, ISAR-TEST 4, LEADERS, NOBORI I, NOBORI I-Phase 2, NOBORI Japan, NOBORI Core, TIVOLI) and not 10. The latter is the number of references these included studies were published in. With an updated literature search in December 2011 we are puzzled as to why the authors cited the older 2009 version of the Cochrane handbook for systematic reviews of interventions, when the latest handbook was released in March 2011. We encourage the authors to refer to the updated Cochrane Collaboration’s tool for assessing risk of bias when appraising the quality of the included studies. We congratulate Lupi et al. for their efforts with this meta-analysis and believe that its findings, subject to clarifications as above, are of significant relevance and interest in the current era of innovative interventional cardiology.

ASSA13-10-19 The Optimal Duration of Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis

<h3>Objective</h3> To assess the efficiency and safety of the use of different dual antiplatelet therapy in patients undergoing percutaneous coronary intervention. <h3>Methods</h3> Cochrane Library, MEDLINE, EMBASE, CBM, CNKI, and VIP, were searched up to October 2011. Randomized controlled trials comparing the efficiency and safety with short duration of treatment (≤6months) versus long duration of treatment ( &gt; 6months) of dual antiplatelet therapy on percutaneous coronary intervention which have been reported were enrolled. No language restriction was enforced. The quality of the included studies was critically evaluated. Data analyses were performed using the Cochrane Collaboration’s RevMan 5.1 software. <h3>Results</h3> Eight trials were included. Three randomised controlled trials and five observational study trials met the inclusion criteria and were incorporated into the primary analysis. Meta-analysis showed that the incidence of death or myocardial infarction in long duration treatment group was lower than short duration treatment group in randomised controlled trials [<i>OR</i> = 0.74, 95% confidence interval [CI] 0.56 to 0.98, <i>P</i> &lt; 0.0001]. Meanwhile, Combined observational studies showed that incidence of death or myocardial infarction in long duration treatment group was lower than short treatment group [<i>OR</i> = 0. 7, 95% confidence interval [CI]0. 45 to 1. 08, <i>P</i> = 0. 11]. We also explored the heterogeneity between the randomised controlled studies and observational studies. In randomised controlled trials, the incidence of major bleeding events of short treatment group was lower than long treatment group [<i>OR</i> = 1.29, 95% confidence interval [CI] 0.99 to 1.69, <i>P</i> = 0.06]. Meta-analysis of observational studies showed that the incidence of late stent thrombosis in long treatment group was lower than short treatment group [<i>OR</i> = 0.40, 95% confidence interval [CI] 0.15 to 1.07, <i>P</i> = 0.07]. <h3>Conclusions</h3> The long duration of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention can reduce the incidence of death or myocardial infarction. There is a trend of decreasing the rate of late stent thrombosis in long treatment group. The incidence of bleeding does not increase obviously in the long treatment group.

Clinical Outcomes from Unselected Real-World Patients with Acute Myocardial Infarction Receiving Biodegradable Polymer Coated Sirolimus-Eluting Stents

Objectives: To investigate clinical outcomes of acute myocardial infarction population in a real-life setting when treated with Indolimus® biodegradable polymer coated sirolimus-eluting coronary stent. Background: Drug-eluting stents in acute myocardial infarction are still feared for possible late and very late stent thrombosis. Newer antiproliferative drugs and more biodegradable polymers have shown promise in reducing further the rate of late stent thrombosis in patients with stable angina. However, limited data is available on the safety and efficacy of biodegradable polymer coated drug-eluting stent in acute myocardial infarction patients. Methods: We studied patients undergoing cardiac catheterization with acute myocardial infarction (n=239) and without acute myocardial infarction (n=291) who had been implanted with Indolimus® sirolimus-eluting stents. The outcomes were reported for 1 and 6-months. The primary endpoint was the composite of major adverse cardiac events at 1 and 6-months after discharge from hospital. The secondary endpoint was stent thrombosis. Results: A higher proportion of patients in the acute myocardial infarction group had renal insufficiency at screening (p=0.02), but there was a higher proportion of patients with a history of myocardial infarction (p<0.001), previous percutaneous coronary intervention (p=0.01) in the non- myocardial infarction group. The frequency of type B2/C lesions (p<0.001) and chronic total occlusion (p<0.001) was higher in the myocardial infarction group. There was no significant difference in parameters related to target vessel distribution and severity of disease. The six months follow-up was completed for 516 (97.4%) enrolled patients. The incidence of any major adverse cardiac events at 6-months was 2.1% and 4.2% for non-myocardial infarction and myocardial infarction population, respectively. There was no stent thrombosis up to 6-months in both groups. Conclusions: In this all-comer, real-world Indolimus acute myocardial infarction study, major adverse cardiac events rates did not differ between acute myocardial infarction and non-acute myocardial infarction population. Six-month observation of acute myocardial infarction treatment using Indolimus® stent compared with non- acute myocardial infarction has no clinical disadvantage. Keywords: Acute myocardial infarction, Percutaneous Coronary Intervention, Sirolmus-eluting stent, biodegradable polymer. Read more →

Biodegradable versus durable polymer drug eluting stents in coronary artery disease: Insights from a meta-analysis of 5834 patients

Biodegradable polymer drug eluting stents (BP-DES) have been developed to overcome the limitations of first generation durable polymer DES (DP-DES) but the clinical results of different BP-DES are not consistent. We performed a meta-analysis to compare the outcomes of BP-DES and DP-DES in the treatment of coronary artery disease (CAD). Online databases including MEDLINE were searched for studies comparing BP-DES and DP-DES for obstructive CAD that reported rates for overall mortality, myocardial infarction (MI), late stent thrombosis (LST), target lesion revascularization (TLR) and late lumen loss (LLL) with a follow-up of ≥ 6 months. Ten studies (5834 patients) with a 1-year median follow-up were included in the meta-analysis. When comparing patients treated with DP-DES and BP-DES those treated with BP-DES had lower LLL (in-stent: weighted mean difference (WMD) -0.10 mm, 95% CI = -0.17 to -0.03 mm, p = 0.004; in-segment: WMD -0.06 mm, 95% CI = -0.10 to -0.01 mm, p = 0.01) with lower TLR rates (OR 0.67, 95% CI = 0.47 to 0.98, p = 0.04). However, BP-DES did not improve mortality (OR 0.97, 95% CI = 0.73 to 1.29, p = 0.83), MI (OR 1.13, 95% CI = 0.87 to 1.46, p = 0.36) or LST rates (OR 0.64, 95% CI = 0.36 to 1.16, p = 0.14). A pre-specified subgroup analysis of Biolimus BP-DES confirmed significant LLL reduction without differences in other clinical endpoints. Meta-regression analysis demonstrated a strong significant inverse correlation between LLL and reference coronary diameter (p < 0.001). Our present meta-analysis showed that BP-DES when compared with DP-DES significantly reduced LLL and TVR but without clear benefits on mortality, MI and LST rates. (Clinicaltrials.gov identifier: NCT01466634).

Usefulness of the RISK-PCI score to predict stent thrombosis in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a substudy of the RISK-PCI trial

Stent thrombosis (ST) is an important cause of death after primary percutaneous coronary intervention (pPCI). This substudy aimed at evaluating the usefulness of the RISK-PCI score, originally developed for the prediction of 30-day major adverse cardiovascular events, to predict the occurrence of ST after pPCI. We analyzed 1972 consecutive patients who underwent pPCI with stent implantation between February 2007 and December 2009. Early ST (EST), late ST (LST), and cumulative 1-year ST (CST) were the predefined end points. Definite, probable, and possible ST were included. Models discrimination and calibration to predict ST was tested using receiver-operating characteristics curves and the goodness-of-fit (GoF) test. Sensitivity analyses and 1000-resample bootstrapping were used to evaluate the model's performance. The rates of EST, LST, and CST were 4.6, 1.4, and 6.0 %, respectively. Compared with controls, the cumulative ST group was associated with much higher rates of adverse clinical outcomes at 30-day follow-up (adjusted odds ratio (OR) for death 6.45, adjusted OR for major bleeding 4.41) and at 12-month follow-up (adjusted OR for death 7.35, adjusted OR for major bleeding 4.56). Internal validation confirmed a reasonably good discrimination and calibration of the RISK-PCI score for the prediction of EST (area under the curve (AUC) 0.71, GoF 0.42), LST (AUC 0.69, GoF 0.36), and CST (AUC 0.70, GoF 0.22) after pPCI. ST after pPCI is associated with adverse 30-day and 1-year clinical outcomes. We conclude that the risk of ST could be accurately assessed using the RISK-PCI score, which might help in deciding upon measures aimed at preventing adverse prognosis.

TWO YEAR CLINICAL OUTCOMES AFTER SIROLIMUS-ELUTING STENT IMPLANTATION FOR THE TREATMENT OF CORONARY ARTERY DISEASE

Abstract Background Coronary artery stents are known to reduce rates of restenosis after coronary stenting, but it is uncertain how long this benefit is maintained. Clinical data has raised concerns that drug-eluting stents are associated with increased rates of late stent thrombosis, death or myocardial infarction. Objectives To evaluate the safety and reliability of sirolimus-eluting stents in real-world practice out to two years. Methods From January 2008 to June 2008, 30 patients were enrolled in the study after implantation of one or more sirolimus-eluting stents. We evaluated clinical follow-up information for up to two years after the implantation of Cypher® Select stents in 30 patients with 35 lesions. Results Mean patient age was 62.33 +/- 10.99 years, 7 percent were diabetic and 30 percent presented with acute myocardial infarctions. The procedure’s success rate was 100 percent for the sirolimus-eluting stent implantation, and follow-up rates were 100 percent. Mean total stent length was 22.32 +/- 6.63 mm, with 13 percent receiving more than one stent. Two year freedom from mortality, myocardial infarction, target vessel revascularization and stent thrombosis was 100 percent. Dual antiplatelet therapy was taken by 100 percent at 1 month, 53 percent at 6 months, 40 percent at 1 year and 0 percent of patients at 2 years. The rate of survival free of myocardial infarction, bypass surgery and repeated angioplasty for stented lesions was 100% at two years. Conclusions Treatment of lesions with sirolimus-eluting stents is associated with a sustained clinical benefit two years after device implantation.

Second-Generation Everolimus-Eluting Stents Versus First-Generation Sirolimus-Eluting Stents in Acute Myocardial Infarction: 1-Year Results of the Randomized XAMI (XienceV Stent vs. Cypher Stent in Primary PCI for Acute Myocardial Infarction) Trial

The goal of this study was to compare the efficacy and safety of second-generation everolimus-eluting stents (EES) with first-generation sirolimus-eluting stents (SES) in primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Drug-eluting stents (DES) in AMI are still feared for possible late and very late stent thrombosis (ST). Newer-generation DES, with more hemocompatible polymers and improved healing, may show promise regarding increased efficacy of DES with improved safety. However, no randomized trials in AMI are available. A total of 625 patients with AMI were randomized (2:1) to receive EES or SES in the XAMI (XienceV Stent vs Cypher Stent in Primary PCI for Acute Myocardial Infarction) trial. Primary endpoint was major adverse cardiac events (MACE) at 1 year consisting of cardiac death, nonfatal AMI, or any target vessel revascularization. The study was powered for noninferiority of EES. Secondary endpoints comprised ST rates and MACE rate up to 3 years. The MACE rate was 4.0% for EES and 7.7% for SES; the absolute difference was -3.7% (95% confidence interval: -8.28 to -0.03; p = 0.048) and relative risk was 0.52 (95% confidence interval: 0.27 to 1.00). One-year cardiac mortality was low at 1.5% for EES versus 2.7% for SES (p = 0.36), and 1-year incidence of definite and/or probable ST was 1.2% for EES versus 2.7% for SES (p = 0.21). In this all-comer, randomized, multicenter AMI trial, second-generation EES was noninferior to SES, and superiority for MACE was suggested. ST rate in EES at 1-year was low, but long-term follow-up and larger studies will have to show whether very late ST rates will also be improved in newer DES. (XienceV Stent vs Cypher Stent in Primary PCI for Acute Myocardial Infarction [XAMI]; NTR1123).

Clinical outcomes of zotarolimus-eluting stents versus the first generation sirolimus-eluting stents and paclitaxel-eluting stents: A meta-analysis of randomized trials

The first generation drug-eluting stents (DES), including the sirolimus-eluting stent (SES) and the paclitaxel-eluting stent (PES), were demonstrated to reduce angiographic restenosis and revascularization compared with the bare-metal stents (BMS) [1]. However, the long-term safety of the two DESs has been questioned by recent studies and a meta-analysis of randomized trials have reported increased rates of late stent thrombosis and late-occurring death or myocardial infarction (MI) compared with BMS [2].

Neutrophil-Derived Cathelicidin Protects from Neointimal Hyperplasia

Percutaneous transluminal angioplasty with stent implantation is used to dilate arteries narrowed by atherosclerotic plaques and to revascularize coronary arteries occluded by atherothrombosis in myocardial infarction. Commonly applied drug-eluting stents release antiproliferative or anti-inflammatory agents to reduce the incidence of in-stent stenosis. However, these stents may still lead to in-stent stenosis; they also show increased rates of late stent thrombosis, an obstacle to optimal revascularization possibly related to endothelial recovery. Here, we examined the contribution of neutrophils and neutrophilic granule proteins to arterial healing after injury. We found that neutrophil-borne cathelicidin (mouse CRAMP, human LL-37) promoted reendothelization and thereby limited neointima formation after stent implantation. We then translated these findings to an animal model using a neutrophil-instructing, biofunctionalized, miniaturized Nitinol stent coated with LL-37. This stent reduced in-stent stenosis in a mouse model of atherosclerosis, suggesting that LL-37 may promote vascular healing after interventional therapy.

Autopsy Validation Study of the Academic Research Consortium Stent Thrombosis Definition

This study sought to validate the sensitivity and specificity of the Academic Research Consortium's (ARC) classification of stent thrombosis. Classification of stent thrombosis according to ARC criteria has become widely accepted. The criteria have not been validated against an autopsy standard. An autopsy registry of 139 subjects with prior coronary stenting underwent detailed histopathological analysis to assess for stent thrombosis. Based on clinical data only, cases were adjudicated according to ARC stent thrombosis criteria, including a proposed modification of the possible classification to include death beyond 30 days due only to sudden death or acute ischemia. Autopsy results confirmed 51 cases as positive and 88 as negative for stent thrombosis. Clinical adjudication classified 105 cases as definite (10), probable (31), or possible (64) ARC stent thrombosis. Specificity was high for definite (99%) and definite plus probable (83%) criteria, but sensitivity was poor at 18% and 51%, respectively. Including the possible cases improved sensitivity to 92% but reduced specificity to 34% (58 false positives). The modified possible criteria eliminated 13 false positive cases (specificity = 49%) and was the best approximation of a hypothetical gold standard in a sensitivity analysis if late death represented at least 20% of all stent thrombosis cases. In a selected autopsy sample, restricting ARC stent thrombosis to definite or definite plus probable criteria results in substantial under-reporting of confirmed cases. Inclusion of a modified possible classification may provide the best estimate of late and very late stent thrombosis rates.

Low Stent Thrombosis Risk with the XIENCE V® Everolimus-Eluting Coronary Stent: Evidence from Randomized and Single-Arm Clinical Trials

The XIENCE V® Everolimus-Eluting Coronary Stent System (EECSS) has been evaluated in multiple randomized controlled trials (RCTs) with several different comparators (SPIRIT FIRST, SPIRIT II, SPIRIT III, SPIRIT IV, COMPARE, ISAR-TEST 4, SORT-OUT IV, and RESOLUTE All-Comers RCT). The available results consistently demonstrated numerically low stent thrombosis (ST) rates in the XIENCE V arm treated patients. The use of XIENCE V in complex patients with diabetes, overlapping stents, multistenting, and other known risk factors has not significantly increased the occurrence of ST, as evident in the 2-year rates of both per protocol and Academic Research Consortium (ARC)-defined ST rates in the SPIRIT IV RCT, as well as the COMPARE real-world RCT. Furthermore, available long-term follow-up in the SPIRIT FIRST, SPIRIT II, and SPIRIT III RCTs showed continued numerically low very late ST rates as well. High compliance rates of dual antiplatelet therapy (DAPT) were observed in the SPIRIT trials, which may have contributed to consistently numerically low ST rates in the XIENCE V arm treated patients. Several potential risk factors for developing ST may well have been minimized through the selective XIENCE V thin strut design, biocompatible polymers, and antiproliferative drug usage. (J Interven Cardiol 2011;24:326-341).