Reduction Of Restenosis Research Articles

Drug-Coated Balloons for Restenosis Prophylaxis

Drug-coated balloons for restenosis prophylaxis provide a high local drug concentration with minimal or no systemic adverse effects. Their development was both delayed and facilitated by the introduction of drug-eluting stents: delayed because sustained release kinetics from stent platforms seemed to be essential and facilitated because prior experience with stents allowed selection of testing methods and drugs. Currently, a variety of drug-coated balloons are available, basically consisting of a coating containing paclitaxel at a dose of about 3 µg/mm² balloon surface, and different additives influencing the adherence and release of the drug, e. g., contrast agent, urea, or various amphiphilic compounds. The drug is almost completely released during a single inflation of 30 - 60 seconds. Studies in animals and several independent randomized clinical trials in coronary and peripheral arteries demonstrate effective reduction of neointimal proliferation, restenosis, and revascularization persisting for at least 2 years or 5 years according to one study in coronary arteries. Drug-coated balloons are preferably used for treating coronary in-stent restenosis and de novo and restenotic lesions in peripheral vessels. No coating-related adverse events have been observed in clinical trials. Persistent efficacy may be explained by the long residence time of paclitaxel in tissue or inhibition of an essential first step in the chain of events leading to neointimal proliferation.

Accelerated endothelialization with a polymer-free sirolimus-eluting antibody-coated stent

Drug-eluting stents have shown an impressive reduction of in-stent restenosis for many years. However, stent thrombosis due to incomplete/late endothelialization has raised major safety concerns. To overcome these problems, we developed for the first time a polymer-free sirolimus-eluting antibody-coated stent (PFSEACS) by combining polymer free and endothelial progenitor cell-capture pro-healing approaches. In the first phase, the stents were prepared by loading sirolimus on the porous outer stent surface and directly fixing the anti-CD34 antibodies without any medium carriers on the blood contacting surface. The dose and elution of sirolimus, the amount and stability of anti-CD34 antibody immobilization, and the rate of CD34+ cell capture were evaluated. In the second phase, the stents were validated in an animal model of coronary arteries in pigs. The stent was observed to start collecting endothelial progenitor cells ~2 h after stent implantation and exhibited greatly enhanced endothelialization while maintaining an excellent anti-restenosis activity comparable to the polymer-free sirolimus-eluting stents. Overall, both in vitro and in vivo evaluations indicated that novel PFSEACSs exhibited facilitated endothelialization with excellent anti-restenosis activity and thus should merit further clinical studies.

Drug-Eluting Balloon in Peripheral Intervention for Below the Knee Angioplasty Evaluation (DEBATE-BTK)

Background— The 1-year restenosis rate after balloon angioplasty of long lesions in below-the-knee arteries may be as high as 70%. Our aim was to investigate the efficacy of a paclitaxel drug-eluting balloons versus conventional percutaneous transluminal angioplasty (PTA) for the reduction of restenosis in diabetic patients with critical limb ischemia undergoing endovascular intervention of below-the-knee arteries. Methods and Results— The Drug-Eluting Balloon in Peripheral Intervention for Below the Knee Angioplasty Evaluation (DEBATE-BTK) is a randomized, open-label, single-center study comparing drug-eluting balloons and PTA. Inclusion criteria were diabetes mellitus, critical limb ischemia (Rutherford class 4 or higher), significant stenosis or occlusion >40 mm of at least 1 below-the-knee vessel with distal runoff, and life expectancy >1 year. Binary in-segment restenosis at a 1-year angiographic or ultrasonographic follow-up was the primary end point. Clinically driven target lesion revascularization, major amputation, and target vessel occlusion were the secondary end points. One hundred thirty-two patients with 158 infrapopliteal atherosclerotic lesions were enrolled. Mean length of the treated segments was 129±83 mm in the drug-eluting balloon group compared with 131±79 mm in the PTA group ( P =0.7). Binary restenosis, assessed by angiography in >90% of patients, occurred in 20 of 74 lesions (27%) in the drug-eluting balloon group compared with 55 of 74 lesions (74%) in the PTA group ( P <0.001); target lesion revascularization, in 12 (18%) versus 29 (43%; P =0.002); and target vessel occlusion, in 12 (17%) versus 41 (55%; P <0.001). Only 1 major amputation occurred, in the PTA group ( P =0.9). Conclusions— Drug-eluting balloons compared with PTA strikingly reduce 1-year restenosis, target lesion revascularization, and target vessel occlusion in the treatment of below-the-knee lesions in diabetic patients with critical limb ischemia. Clinical Trial Registration— URL: http://ClinicalTrials.gov . Unique identifier: NCT01558505.

Myokardrevaskularisation

Coronary artery disease (CAD) is a leading cause of morbidity and mortality in western countries and is of significant socio-economic importance due to its increasing prevalence. Until percutaneous coronary interventions (PCI) were established, CAD could only be treated by surgical revascularization or pharmacological therapy. In-stent restenosis remains a major problem after stent implantation. However, the use of new materials and stent coatings have led to a significant reduction in in-stent restenosis. Thus, surgical revascularization and PCI are currently of equal value for the treatment of CAD. The decision-making for PCI or surgical revascularization depends on various factors such as number of diseased vessels, complexity of the coronary stenoses, concomitant diseases, and the patient's general condition. The therapeutic regime of every patient should be adjusted to the recommendations of the European and German Society for Cardiology, while controversial and complex cases should be discussed in an interdisciplinary case conference ("heart team").

Xiongshao for restenosis after percutaneous coronary intervention in patients with coronary heart disease.

Percutaneous coronary intervention (PCI) with stent placement is a standard treatment for coronary heart disease (CHD). In-stent restenosis after PCI remains an important clinical problem. Xiongshao capsule has been reported to be beneficial in preventing restenosis after PCI in CHD patients. However, the strength of evidence to support its use is unclear. To systematically assess the efficacy and safety of Chinese herbal medicine Xiongshao capsule in preventing restenosis after PCI in patients with CHD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3 of 2012), MEDLINE (OVID) (1948 to week 1 March 2012), EMBASE (OVID) (1980 to week 10 2012), ISI Web of Science with Conference Proceedings (1970 to 14 March 2012), LILACS (1982 to 15 March 2012), Chinese biomedical literature database (1980 to May 2012), China National Knowledge Infrastructure (1994 to May 2012), Chinese Medical Current Contents (1994 to May 2012), VIP Database for Chinese Technical Periodicals (1989 to May 2012), Chinese Master's Theses Full-Text Database (1994 to May 2012), China Doctor Dissertation Full-Text Database (1994 to May 2012), and China Proceedings of Conference Full-Text Database (1994 to May 2012). We also searched ongoing trials and research registries. All randomised controlled trials comparing Xiongshao capsule alone/plus conventional western medicine with the same conventional western medicine alone/plus placebo in participants with CHD who met the recognised diagnostic criteria and had successfully undergone a PCI procedure were included. Two review authors independently selected trials and extracted data. Two review authors independently assessed the risk of bias of included trials using The Cochrane Collaboration tool, and any disagreements were resolved by discussion with a third review author. Data were pooled for meta-analysis using the fixed-effect model, and the results were expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Four trials involving 649 participants were included in this review. Two of these trials (459 participants) were designed as randomised, double-blind, placebo-controlled trials with an adequate methodological description; the other two trials (190 participants) described an inadequate methodological design. All four trials with 649 participants were included in the meta-analysis. Significant differences were noted in rates of restenosis, recurrence angina pectoris, and serious cardiovascular adverse events between Xiongshao capsule plus conventional western medicine and the same conventional western medicine alone; RR values (95% CIs) were 0.41 (0.22 to 0.75), 0.47 (0.31 to 0.72), and 0.47 (0.25 to 0.90), respectively. Xiongshao capsule plus conventional western medicine showed more significant reductions in restenosis (RR 0.52, 95% CI 0.33 to 0.80), recurrence angina pectoris (RR 0.26, 95% CI 0.18 to 0.38), and serious cardiovascular adverse events (RR 0.45, 95% CI 0.28 to 0.70) than the same conventional western medicine plus placebo. Safety outcomes and adverse events of the Xiongshao capsule were reported in two trials, which reported no adverse events. The summary estimates indicate a protective effect of Xiongshao on restenosis and suggest that Xiongshao capsule may be used to prevent restenosis after a PCI procedure in CHD patients. However, this evidence is derived from small randomised trials, all conducted in China, and two of the included trials showed important methodological limitations that undermine the validity of the findings. Additional high-quality research trials with sufficient sample size are required.

Biological responses in stented arteries

Vascular walls change their dimension and mechanical properties in response to injury such as balloon angioplasty and endovascular stent implantation. Placement of bare metal stents induces neointimal proliferation/restenosis which progresses through different phases of repair with time involving a cascade of cellular reactions. These phases just like wound healing comprise distinct steps consisting of thrombosis, inflammation, proliferation, and migration followed by remodelling. It is noteworthy that animals show a rapid progression of healing after stent deployment compared with man. During stenting, endothelial cells are partially to completely destroyed or crushed along with medial wall injury and stretching promoting activation of platelets, and thrombus formation accompanied by inflammatory reaction. Macrophages and platelets play a central role through the release of cytokines and growth factors that induce vascular smooth muscle cell accumulation within the intima. Smooth muscle cells undergo complex phenotypic changes including migration and proliferation from the media towards the intima, and transition from a contractile to a synthetic phenotype; the molecular mechanisms responsible for this change are highlighted in this review. Since studies in animals and man show that smooth muscle cells play a dominant role in restenosis, drugs like rapamycin and paclitaxel have been coated on stent with polymers to allow local slow release of drugs, which have resulted in dramatic reduction of restenosis that was once the Achilles' heel of interventional cardiologists.

Part One: For the Motion. Completion Angiography Should be Used Routinely Following Carotid Endarterectomy

Part One: For the Motion. Completion Angiography Should be Used Routinely Following Carotid Endarterectomy

A randomized multicentre study comparing a paclitaxel drug-eluting balloon with a paclitaxel-eluting stent in small coronary vessels: The BELLO (Balloon Elution and Late Loss Optimization) study

Objectives: The aim of this study was to evaluate the efficacy of drug-eluting balloons (DEB) compared with paclitaxel eluting stents (PES) for the reduction of restenosis in small vessels. Background: DEB have been shown to be effective in the treatment of coronary in-stent restenosis, but data are limited regarding their efficacy in de-novo disease. Methods: BELLO (Balloon Elution and Late Loss Optimization) is a prospective, multicentre trial that randomized 182 patients with lesions located in small vessels (reference diameter <2.8 mm) to treatment with paclitaxel DEB and provisional bare-metal stenting (n = 90) or PES implantation (n = 92). The primary endpoint was noninferiority of angiographic in-stent (in-balloon) late loss with a delta of 0.25 mm. Secondary end-points were angiographic restenosis, target lesion revascularization, and major adverse cardiac events (MACE; death, myocardial infarction, target vessel revascularization) at 6 months. Results: Baseline characteristics were well matched, except for a smaller vessel size in the DEB group (2.15 ± 0.27 mm vs. 2.25 ± 0.24 mm; p = 0.003). The majority (89%) of lesions involved vessels with a diameter<2.5 mm. Bailout stenting was required in 20% of lesions in the DEB group. The primary endpoint of in-stent (in-balloon) late loss was significantly less with DEB compared with PES (0.08 ± 0.38 mm vs. 0.29 ± 0.44 mm; difference −0.21; 95% CI: −0.34 to −0.09; p noninferiority < 0.001; p superiority = 0.001). At 6 months, DEB and PES were associated with similar rates of angiographic restenosis (8.9% vs. 14.1%; p = 0.25), target lesion revascularization (4.4% vs. 7.6%; p = 0.37), and MACE (7.8% vs. 13.2%; p = 0.77). Conclusions: Treatment of small-vessel disease with a paclitaxel DEB was associated with less angiographic late loss and similar rates of restenosis and revascularization as a PES.

Individualization of dual antiplatelet therapy duration after drug-eluting stent implantation: paradigm and reality

This editorial refers to ‘Should duration of dual antiplatelet therapy depend on type and/or potency of implanted stent? A pre-specified analysis from the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY)’[†][1], by M. Valgimigli et al. , on page 909 The use of drug-eluting stents (DES) results in a dramatic reduction in restenosis and represents one of the major advances in interventional cardiology. Yet, a reduction in death and myocardial infarction could not be shown with these devices; instead there were concerns about an excess of late thrombotic events compared with bare metal stents (BMS).1 The key underlying pathophysiological mechanism was suggested to be delayed arterial healing after DES implantation.2 Several non-randomized studies found controversial results regarding the duration of dual antiplatelet therapy (DAPT) and its impact on the risk of stent thrombosis.3,4 Since different stent platforms show different vessel healing5 and antiproliferative properties, it has been suggested that those with less antiproliferative properties (i.e. reduced efficacy) offer improved vascular healing (i.e. safety).6 The importance of DAPT in the early post-procedural period is well evidenced.7 However, the optimal time point when the benefit of preventing ischaemic events is outweighed by an increased bleeding risk has not been reliably defined. This controversy is also reflected in the different recommendations for DAPT duration after DES implantation by the guidelines committees on both sides of the Atlantic.8,9 Yet despite being much debated in the DES era, the problem of defining the optimal duration of DAPT for patients with coronary artery disease is … [1]: #fn-2

Clinical outcome after endovascular treatment for isolated common femoral and popliteal artery disease

The safety and patency of endovascular treatment (EVT) in isolated common femoral artery (CFA) and popliteal artery (PA) remain poorly understood. We investigated the efficacy after EVT for isolated CFA and PA disease. This study was performed as a multicenter retrospective registry of a prospectively maintained database. Between January 2001 and December 2010, consecutive 183 patients (214 lesions; CFA 111, PA 103) who received endovascular procedure for de novo isolated CFA and PA disease were enrolled. The main endpoints of this study were primary and secondary patency after EVT. Procedure success was 95.8%. The 1- and 5-year primary patencies for CFA (PA) lesions after EVT were 73.5% (75.5%) and 46.9% (56.2%), respectively. There was no significant difference of primary patency rate between CFA and PA (46.9 vs. 56.2% at 5-year, p=0.83). However, secondary patency significantly differed between CFA and PA (97.6 vs. 86.2% at 5-year, p=0.009). Stent placement was not effective for the reduction of restenosis in both CFA and PA lesion. On multivariate analysis to define the predictors of primary patency for the CFA, renal failure, coronary artery disease, calcified lesion and residual stenosis after EVT were independent predictors. Also, the predictors of primary patency for the PA were BMI, reference vessel diameter, anemia and residual stenosis after EVT. Short-term patency after EVT for isolated CFA and PA lesion seems to be feasible. However, long-term patency was not promising. Furthermore, stent placement does not improve the primary patency.

Angioplasty guided by intravascular ultrasound: meta-analysis of randomized clinical trials.

BackgroundThe impact of intravascular ultrasound (IVUS) use on stenting has shown inconclusive results.ObjectiveSystematic review and meta-analysis of the impact of IVUS on stenting regarding the clinical and angiographic evolution.MethodsA search was performed in Medline/Pubmed, CENTRAL, Embase, Lilacs, Scopus and Web of Science databases. It included randomized clinical trials (RCTs) that evaluated the implantation of stents guided by IVUS, compared with those using angiography alone (ANGIO). The minimum follow-up duration was six months and the following outcomes were assessed: thrombosis, mortality, myocardial infarction, percutaneous and surgical revascularization, major adverse cardiovascular events (MACE) and restenosis. The binary outcomes were presented considering the number of events in each group; the estimates were generated by a random effects model, considering Mantel-Haenszel statistics as weighting agent and magnitude of effect for the relative risk (RR) with its respective 95% confidence interval (95%CI). Higgins I2 test was used to quantify the consistency between the results of each study.ResultsA total of 2,689 articles were evaluated, including 8 RCTs. There was a 27% reduction in angiographic restenosis (RR: 0.73, 95% CI: 0.54-0.97, I2 = 51%) and statistically significant reduction in the rates of percutaneous revascularization and overall (RR: 0.88; 95% CI: 0.51 to 1.53, I2 = 61%, RR: 0.73, 95% CI: 0.54 to 0.99, I2 = 55%), with no statistical difference in surgical revascularization (RR: 0.95, 95% CI: 0.52-1.74, I2 = 0%) in favor of IVUS vs. ANGIO. There were no differences regarding the other outcomes in the comparison between the two strategies. ConclusionAngioplasty with stenting guided by IVUS decreases the rates of restenosis and revascularization, with no impact on MACE, acute myocardial infarction, mortality or thrombosis outcomes.

Zastosowanie stentów uwalniających leki w świeżym zawale serca – czy batalia dobiega końca? Od zwątpienia do aprobaty

The large-scale use of drug-eluting stents (DES) in elective percutaneous coronary interventions resulted in a significant reduction of restenosis and the need for repeat revascularization, compared to bare-metal stents (BMS) and balloon angioplasty. The position of DES used during primary percutaneous coronary intervention was not so well established. Based on the trials including the general population of patients, an increased risk of stent thrombosis was indicated, particularly late after implantation, which may be associated with increased mortality. A number of randomized clinical trials have compared first generation DES with BMS in acute ST-segment elevation myocardial infarction (STEMI). In most of them increased mortality after DES implantation was not confirmed, with demonstrated reduction of repeat revascularizations. However, long-term follow-up of these studies and the results from non-randomized “real world” registries are equivocal. A new generation of DES has been present on the market for several years. They have modern designs, are covered with more neutral polymers and release new drugs. The new generation DES have a better safety and efficacy profile, including a population of patients with acute STEMI, than the first generation stents. This paper is a review of randomized controlled trials, meta-analyses and registries, comparing DES with BMS in patients with acute STEMI. Attention was drawn to the current position and the role of new generation DES, which may prove to be a safe and effective choice in this population of patients.

Superparamagnetic iron oxide nanoparticle targeting of MSCs in vascular injury

Vascular occlusion can result in fatal myocardial infarction, stroke or loss of limb in peripheral arterial disease. Interventional balloon angioplasty is a common first line procedure for vascular disease treatment, but long term success is limited by restenosis and neointimal hyperplasia. Cellular therapies have been proposed to mitigate these issues; however efficacy is low, in part due to poor cell retention. We show that magnetic targeting of mesenchymal stem cells gives rise to a 6-fold increase in cell retention following balloon angioplasty in a rabbit model using a clinically applicable permanent magnet. Cells labelled with superparamagnetic iron oxide nanoparticles exhibit no negative effects on cell viability, differentiation or secretion patterns. The increase in stem cell retention leads to a reduction in restenosis three weeks after cell delivery.

Current status and future prospects of drug eluting stents for restenosis / Sadašnjost i budućnost stentova za restenozu koji otpuštaju lijekove

Drug-eluting stents (DESs) prevail in the treatment of carotid artery diseases in the interventional cardiology world owing to their efficacy for significant reduction of restenosis. A current successful DES requires a polymer coating for drug delivery. Clinical trials examining several pharmaceutical agents have demonstrated marked reduction in restenosis following stenting. The development of DES is one of the major revolutions in the field of interventional cardiology. The ideal drug to prevent restenosis must have an anti-proliferative and anti-migratory effect on smooth muscle cells but, on the other hand, it must also enhance re-endothelialization in order to prevent late thrombosis. Additionally, it should effectively inhibit the anti-inflammatory response after balloon induced arterial injury. Although DES have significantly reduced the angiographic restenosis rate and have improved clinical outcomes, late thrombosis and restenosis remain an important subject of ongoing research.

Effects of plasma treatments on the controlled drug release from poly(ethylene-co-vinyl acetate)

Plasma surface treatment was investigated as a surface modification method for a drug-eluting stent (DES) coated with polymers. Currently, the implantation of the DES is the most efficient way to treat a coronary artery disease. DES elutes anti-proliferative drugs that suppress proliferation of smooth muscle cells in the stented segment of the artery. Despite the impressive reduction in restenosis by DES, it still occasionally has a major disadvantage for not preventing restenosis at an implant site due to the relatively vast drug release from the stent surface in the early stages of the drug release. To solve the problem, we studied plasma treatments on the polymer surface because there would not be a substantial risk of damaging the bulk properties of the polymer and the stent by plasma surface treatments. In this study, argon, oxygen, and nitrogen were selected as working gases and poly(ethylene-co-vinyl acetate) (EVA), a hydrophobic biomedical polymer, was selected as a base drug-reservoir material for DES. Structural analyses were carried out by water contact angle measurements, X-ray photon spectroscopy (XPS), and the evaluation of the crosslinking degree of EVA polymer. It was found that the initial burst-release and the cumulative released amount of the drug were both effectively suppressed by controlling the plasma processing time. Furthermore, less effective control of the drug release was obtained by using nitrogen or oxygen plasma as a processing gas instead of argon plasma. According to the evaluation of the crosslinking degree, it was found that argon plasma could most effectively induce the crosslinking in EVA, while nitrogen and oxygen plasmas came in second and third, respectively, which corresponded to the results of the drug release experiments. It was expected that the experimental results of the plasma treatments could provide a new and alternative approach to a controllable and sustainable drug release system.

Reduced myofibroblast differentiation on femtosecond laser treated 316LS stainless steel

In-stent restenosis is a common complication after stent surgery which leads to a dangerous wall narrowing of a blood vessel. Laser assisted patterning is one of the effective methods to modify the stent surface to control cell–surface interactions which play a major role in the restenosis. In this current study, 316LS stainless steel substrates are structured by focusing a femtosecond laser beam down to a spot size of 50μm. By altering the laser induced spot density three distinct surfaces (low density (LD), medium density (MD) and high density (HD)) were prepared. While such surfaces are composed of primary microstructures, due to fast melting and re-solidification by ultra-short laser pulses, nanofeatures are also observed as secondary structures. Following a detailed surface characterization (chemical and physical properties of the surface), we used a well-established co-culture assay of human microvascular endothelial cells and human fibroblasts to check the cell compatibility of the prepared surfaces. The surfaces were analyzed in terms of cell adherence, proliferation, cell morphology and the differentiation of the fibroblast into the myofibroblast, which is a process indicating a general fibrotic shift within a certain tissue. It is observed that myofibroblast proliferation decreases significantly on laser treated samples in comparison to non-treated ones. On the other hand endothelial cell proliferation is not affected by the surface topography which is composed of micro- and nanostructures. Such surfaces may be used to modify stent surfaces for prevention or at least reduction of restenosis.

A Randomized Multicenter Study Comparing a Paclitaxel Drug-Eluting Balloon With a Paclitaxel-Eluting Stent in Small Coronary Vessels: The BELLO (Balloon Elution and Late Loss Optimization) Study

The aim of this study was to evaluate the efficacy of drug-eluting balloons (DEB) compared with paclitaxel-eluting stents (PES) for the reduction of restenosis in small vessels. DEB have been shown to be effective in the treatment of coronary in-stent restenosis, but data are limited regarding their efficacy in de novo disease. BELLO (Balloon Elution and Late Loss Optimization) is a prospective, multicenter trial that randomized 182 patients with lesions located in small vessels (reference diameter <2.8 mm) to treatment with paclitaxel DEB and provisional bare-metal stenting (n = 90) or PES implantation (n = 92). The primary endpoint was noninferiority of angiographic in-stent (in-balloon) late loss with a delta of 0.25 mm. Secondary endpoints were angiographic restenosis, target lesion revascularization, and major adverse cardiac events (MACE; death, myocardial infarction, target vessel revascularization) at 6 months. Baseline characteristics were well matched, except for a smaller vessel size in the DEB group (2.15 ± 0.27 mm vs. 2.25 ± 0.24 mm; p = 0.003). The majority (89%) of lesions involved vessels with a diameter <2.5 mm. Bailout stenting was required in 20% of lesions in the DEB group. The primary endpoint of in-stent (in-balloon) late loss was significantly less with DEB compared with PES (0.08 ± 0.38 mm vs. 0.29 ± 0.44 mm; difference -0.21; 95% CI: -0.34 to -0.09; p(noninferiority) < 0.001; p(superiority) = 0.001). At 6 months, DEB and PES were associated with similar rates of angiographic restenosis (10% vs. 14.6%; p = 0.35), [corrected] target lesion revascularization (4.4% vs. 7.6%; p = 0.37), and MACE (10% vs. 16.3%; p = 0.21). [corrected]. Treatment of small-vessel disease with a paclitaxel DEB was associated with less angiographic late loss and similar rates of restenosis and revascularization as a PES. (Balloon Elution and Late Loss Optimization [BELLO]; Study NCT01086579).

Optimal duration of clopidogrel therapy: the shorter the longer?

This editorial refers to ‘Clinical impact of extended dual antiplatelet therapy after percutaneous coronary interventions in the drug-eluting stent era: a meta-analysis of randomized trials’, by S. Cassese et al. , doi:10.1093/eurheartj/ehs318 After the initial enthusiasm for drug-eluting stents (DES) based on their impressive reduction in restenosis, there was increasing concern about an increased and sustained risk for stent thrombosis ( Figure 1 ). Consequently, the recommendation for the duration of dual antiplatelet therapy (DAPT) was gradually extended from initially 3 months for sirolimus-eluting stents (SES) and 6 months for paclitaxel-eluting stents (PES) to currently at least 12 months for all DES. This recommendation is reinforced by most cardiovascular societies including the American College of Cardiology (ACC)/American Heart Association (AHA) and the National Institute for Health and Clinical Excellence (NICE) in the UK, while the European ESC guidelines recommend at least 6–12 months of DAPT for DES,1 and at least 12 months after an acute coronary syndrome (ACS) regardless of stent type.2 Not uncommonly, cardiologists recommend indefinite DAPT if the patient has no bleeding complications during the first 12 months. The need for long-term DAPT is costly and remains the Achilles' heel of DES; furthermore, the excess risk for stent thrombosis associated with DES is a matter of an ongoing controversy. Ongoing improvements in second- and third-generation DES drug coatings as well as other factors such as stent design may have all changed the rates of stent thrombosis. Newer generation stents have shown impressively low stent thrombosis rates and, therefore, the excessive bleeding risk of DAPT has to be reconsidered.3,4 The newest generation everolimus-eluting stents (EES) have revealed very low stent thrombosis rates,3 and, in Europe, Abbott's Xience V and Xience PRIME stents have recently received the CE mark with 3 months DAPT, further adding to the …

The impact of successful manual thrombus aspiration on in-stent restenosis after primary PCI

This study sought to investigate the impact of successful manual thrombus aspiration on angiographic in-stent restenosis and clinical outcome in patients treated by bare metal stent implantation for ST-segment elevation acute myocardial infarction. There are very limited data on the impact of manual thrombus aspiration on the occurrence of in-stent restenosis after bare metal stent implantation. This was a prospective, randomized, single-center study. Patients (N=60) presenting within 12 h of ST-segment elevation acute myocardial infarction symptom onset were randomized to primary percutaneous coronary intervention (PCI) with (N=30) or without (N=30) upfront manual thrombus aspiration using the Export aspiration catheter. All patients underwent control coronary angiography after 6 months. Baseline, clinical, and angiographic preprocedural findings did not differ between the two groups. Patients who underwent successful manual thrombus aspiration had significantly higher minimal lumen diameter after 6 months (2.25±0.90 vs. 1.63±0.76, P=0.005), significantly lower percentage diameter stenosis (28.81 vs. 45.03%, P=0.017), and significantly lower late lumen loss (0.73±0.84 vs. 1.18±0.79, P=0.035). There was a trend for lower rate of major adverse cardiocerebrovascular events such as death, myocardial reinfarction, stroke, and target lesion revascularization in the same group of patients (16.67 vs. 26.67%, P=0.347). Successful upfront manual thrombus aspiration during primary PCI showed beneficial effects on the reduction of in-stent restenosis after bare metal stent implantation compared with standard PCI.

Suppression of Neointimal Hyperplasia Following Angioplasty-Induced Vascular Injury in Pigs Infected with Swinepox Virus

Many patients suffering from angina pectoris are treated with percutaneous coronary intervention (PCI) and quickly develop angiographic renarrowing, or restenosis, at the site of PCI treatment. Restenosis is thought to arise from the combinatorial activation of thrombotic and inflammatory responses. The inflammatory response responsible for restenosis is also thought to involve the activation of a cascade of serine proteases and its subsequent regulation. Poxviruses are known to possess a variety of immunomodulatory strategies, some of which target serine proteases, cytokines, and chemokines. To this end we evaluated whether systemic species-specific swinepox virus (SPV) infection could induce sufficient host-immune modulation to promote an anti-inflammatory and anti-proliferative effect, thereby preventing restenosis. Two groups of domestic feeder pigs were used - the first group was experimentally infected with SPV (n= 11) and the second group served as an uninfected control (n= 5). A week after infection, the pigs were anesthetized and percutaneous transluminal coronary angioplasty (PTCA) was performed in the left anterior descending coronary artery using X-ray fluoroscopy to visualize the balloon and record angiograms. Three weeks post infection, the pigs were euthanized and balloon angioplasty injured arteries were harvested and examined. We observed a statistically significant reduction of restenosis in SPV-infected pigs (p = 0.05) compared to control pigs and conclude that systemic swinepox virus infection causes sufficient host immune suppression to significantly reduce restenosis in pigs after balloon angioplasty injury.