De-novo Coronary Lesions Research Articles

Response to Letters Regarding Article, “Two-Year Clinical Outcomes With Drug-Eluting Stents for Diabetic Patients With De Novo Coronary Lesions: Results From a Real-World Multicenter Registry”

We thank Barlis and colleagues for their legitimate1 query about the ability of the propensity score regression technique to balance covariates between the somewhat heterogeneous groups. Our decision to report the results of a propensity score regression analysis conducted across the overall study population was based on a number of considerations. Nevertheless, application of propensity score matching (as suggested by Barlis and colleagues) in 2 well-balanced but smaller groups (253 patients each) substantially confirms the main results. Indeed, the result for the main …

Letter by Watada et al Regarding Article, “Two-Year Clinical Outcomes With Drug-Eluting Stents for Diabetic Patients With De Novo Coronary Lesion”

To the Editor: We read with interest the article by Dr Ortolani and coworkers1 on the results of their study of 2-year clinical outcome of drug-eluting stents for diabetic patients. They concluded that the use of drug-eluting stents was associated with a modest reduction in the 2-year risk of target vessel revascularization compared with the use of bare-metal stents. In their study, a significant reduction in risk of major adverse cardiac events by drug-eluting stent implantation was identified in non-insulin-dependent diabetic …

Letter by Barlis et al Regarding Article, “Two-Year Clinical Outcomes With Drug-Eluting Stents for Diabetic Patients With De Novo Coronary Lesions: Results From a Real-World Multicenter Registry

To the Editor: The role of drug-eluting stents within the field of interventional cardiology has recently come under close scrutiny in the wake of increasing concerns about late stent thrombosis and doubts on the overall cost-effectiveness of these devices. The prevailing view among experts, however, is that this technology retains an important role, particularly in patients at high risk of restenosis such as those with diabetes mellitus, as suggested by randomized trials.1 It was thus with great interest that we read the article by Ortolani et al,2 which presents the results …

Preliminary Results of the Hydroxyapatite Nonpolymer-Based Sirolimus-Eluting Stent for the Treatment of Single De Novo Coronary Lesions: A First-in-Human Analysis of a Third-Generation Drug-Eluting Stent System

We sought to investigate the performance and efficacy of the third-generation polymer-free Vestasync-eluting stent (VES). Recent concerns regarding the long-term safety of drug-eluting stents have been raised. Synthetic polymers have been associated with intensive inflammatory response and late stent thrombosis. Newly developed, the VES combines a stainless steel platform with a nanothin-microporous hydroxyapatite surface coating impregnated with a polymer-free sirolimus formulation (55 mum). In May 2007, 15 patients with single de novo lesion located in native coronary arteries 3.0 to 3.5 mm in diameter and < or =14 mm in length were consecutively enrolled. Primary end points included in-stent late lumen loss and in-stent percent of obstruction at 4 months. Serial angiography and intravascular ultrasound were obtained at the index procedure and repeated at 4-month follow-up. Mean population age was 63.8 years; 33% of patients were diabetic. The left anterior descending artery was the prevalent target vessel (47%). Reference vessel diameter and lesion length were 2.67 +/- 0.32 mm and 9.98 +/- 1.98 mm, respectively. The VES was successfully implanted in all cases, and there were no procedure and in-hospital complications. Life-long aspirin and 6-month clopidogrel therapy were prescribed for all patients. At 4 months, in-stent late lumen loss was 0.30 +/- 0.25 mm and percent of stent obstruction was 2.8 +/- 2.2%. After up to 6 months of clinical follow-up, no major adverse cardiac event was registered. The third-generation VES demonstrated excellent acute results in the treatment of de novo coronary lesions. Longer follow-up with a more complex subset of patients and lesions is required to confirm these preliminary results.

Association of Insulin Resistance with de novo Coronary Stenosis after Percutaneous Coronary Artery Intervention in Hemodialysis Patients

Background/Aims: De novo coronary atherosclerosis may be involved in the poor prognosis after percutaneous coronary artery intervention (PCI) in hemodialysis patients. We aimed to clarify the factors associated with de novocoronary lesion in this population. Methods: We enrolled 106 patients on hemodialysis (72 men, 34 women; mean age, 65.4 ± 8.9 years), who had firstly received PCI with bare-metal stents for single coronary lesions and undergone follow-up coronary angiography (CAG) 6 months thereafter. Coronary lesion with stenosis of >50% diameter that was newly recognized at follow-up CAG was defined as de novo coronary stenosis. The values of biochemical parameters were determined as the means of several measurements between PCI and follow-up CAG. Results: Follow-up CAG revealed de novo coronary stenosis in 40 (37.7%) of the 106 hemodialysis patients who had received PCI. Stepwise multiple logistic regression analysis showed that de novo coronary lesions were strongly associated with homeostasis model assessment insulin resistance index (HOMA-IR; 1 mM× [µU/ml]: odds ratio, 7.312; p =0.001). This significant association of HOMA-IR with de novo coronary stenosis was recognized in the diabetic and nondiabetic subgroups. Conclusions: Insulin resistance may be involved in the progression of nonculprit coronary atherosclerosis after PCI in hemodialysis patients.

A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial

A fully bioabsorbable drug-eluting coronary stent that scaffolds the vessel wall when needed and then disappears once the acute recoil and constrictive remodelling processes have subsided has theoretical advantages. The bioasorbable everolimus-eluting stent (BVS) has a backbone of poly-L-lactic acid that provides the support and a coating of poly-D,L-lactic acid that contains and controls the release of the antiproliferative agent everolimus. We assessed the feasibility and safety of this BVS stent. In this prospective, open-label study we enrolled 30 patients who had either stable, unstable, or silent ischaemia and a single de-novo lesion that was suitable for treatment with a single 3.0 x 12 mm or 3.0 x 18 mm stent. Patients were enrolled from four academic hospitals in Auckland, Rotterdam, Krakow, and Skejby. The composite endpoint was cardiac death, myocardial infarction, and ischaemia-driven target lesion revascularisation. Angiographic endpoints were available for 26 patients and intravascular-ultrasound endpoints for 24 patients. Clinical endpoints were assessed in all 30 patients at 6 and 12 months. In a subset of 13 patients, optical coherence tomography was undertaken at baseline and follow-up. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00300131. Procedural success was 100% (30/30 patients), and device success 94% (29/31 attempts at implantation of the stent). At 1 year, the rate of major adverse cardiac events was 3.3%, with only one patient having a non-Q wave myocardial infarction and no target lesion revascularisations. No late stent thromboses were recorded. At 6-month follow-up, the angiographic in-stent late loss was 0.44 (0.35) mm and was mainly due to a mild reduction of the stent area (-11.8%) as measured by intravascular ultrasound. The neointimal area was small (0.30 [SD 0.44] mm2), with a minimal area obstruction of 5.5%. This study shows the feasibility of implantation of the bioabsorbable everolimus-eluting stent, with an acceptable in-stent late loss, minimal intrastent neointimal hyperplasia, and a low stent area obstruction. Abbott Vascular.

Two-Year Clinical Outcomes With Drug-Eluting Stents for Diabetic Patients With De Novo Coronary Lesions

The long-term effectiveness of drug-eluting stents (DES) in unselected diabetics in routine practice is currently unclear. To evaluate the long-term effectiveness of bare metal stents and DES in a real-world setting of diabetic patients, we analyzed 2-year follow-up data from all diabetic patients with de novo lesions enrolled in a prospective Web-based multicenter registry (Registro Regionale Angioplastiche dell'Emilia-Romagna; study period, 2002 to 2004) comprising all 13 hospitals performing percutaneous coronary interventions in the Emilia-Romagna region of Italy. Among the 1648 eligible patients treated with either bare metal stents alone (n=1089) or DES alone (n=559), 27% were insulin dependent and 83% had multivessel coronary disease. At 2 years, use of DES was associated with lower crude incidence of major adverse cardiac advents (all-cause mortality, nonfatal myocardial infarction, and target vessel revascularization) compared with bare metal stents (22.5% versus 28.1%; P=0.01). After propensity score adjustment, only target vessel revascularization appeared significantly lower in the DES group (11.6% versus 15.0%; hazard ratio, 0.66; 95% confidence interval, 0.46 to 0.96; P=0.041). Two-year angiographic stent thrombosis occurred in 1.5% DES patients and 0.7% of the bare-metal-stents patients (P=0.18). At Cox regression analysis, predictors of 2-year major adverse cardiac advents were left ventricular ejection fraction <35%, Charlson comorbidity index, insulin-dependent diabetes, and total lesion length. In this large, real-world, diabetic population, the use of DES was associated with a moderate reduction in the 2-year risk of target vessel revascularization, a benefit that was limited to non-insulin-dependent diabetic patients. Larger long-term studies are needed to clarify the long-term effectiveness and safety of such devices in diabetic patients.

Impact of metabolic syndrome on clinical and angiographic outcome after sirolimus-eluting stent implantation

Patients with metabolic syndrome (MetS) are at increased risk of cardiovascular events. The impact of MetS on clinical events and restenosis after drug-eluting stent placement is not well defined. Two hundred and seventy-four consecutive patients with 298 de-novo coronary lesions (<50 mm lesion length, reference diameter<3.5 mm) successfully treated with sirolimus-eluting stents (SES) were enrolled in the study. Bifurcation lesions, left main lesions and ST-segment elevation myocardial infarcts were excluded. Patients were categorized into three groups: (i) diabetes, (ii) MetS without diabetes, (iii) controls without MetS or diabetes. MetS was defined as presence of > or =3 of the following criteria: obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, raised fasting glucose. One hundred and twenty-one patients (44%) with 134 lesions had neither MetS nor diabetes, 84 patients (31%) with 89 lesions had MetS without diabetes and 69 patients (25%) with 75 lesions had diabetes. Baseline angiographic parameters were comparable between the three groups. Clinically driven target lesion revascularization rates and major adverse cardiac event rates at 12 months were 1, 1, 7% (P=0.039) and 3, 6 and 14% (P=0.032), respectively, for controls, patients with MetS/no diabetes and diabetic patients. Follow-up angiography at 6 months demonstrated late loss in lesion, which was 0.10+/-0.33 mm in the controls, 0.10+/-0.20 mm in patients with MetS/no diabetes and 0.36+/-0.66 mm in diabetic patients (P=0.009). MetS without diabetes does not result in an increase in target lesion revascularization, major adverse cardiac event rates or angiographic late loss compared with control patients after implantation of SES in de-novo coronary lesions.

The Paclitaxel-Eluting Coroflex™ Please Stent Pilot Study (PECOPS I)

The alleged superiority of drug-eluting stents over bare metal devices and those with passive coatings is diminished by a higher incidence of late target vessel thrombosis. Therefore, the one-year clinical outcome of the paclitaxel-eluting Coroflex Please stent in patients with denovo coronary lesions was evaluated in the single-arm PECOPS I pilot study. The clinical data of 96/97 (99%) of the patients included per protocol and of 86/87 (98.9%) of those treated per protocol were available 13.1 +/- 1.8 months following stent deployment. In the inclusion and treatment per protocol groups the incidence of cardiac deaths was 1/96 (1%) and 1/86 (1.2%), of myocardial infarction 3/96 (3.1%) and 1/86 (1.2%), and of target lesion revascularization 9/96 (9.4%) and 8/86 (9.3%). In patients enrolled per protocol two early thromboses (2.1%) occurred one of which two days after premature discontinuation of clopidogrel. In patients treated per protocol one thrombosis was observed after 10 hours. The one-year event-free survival was 83/96 (86.5%) in patients enrolled per protocol and 75/86 (87.2%) in those treated per protocol. The one-year clinical outcome of PECOPS I was within the range of other paclitaxel-eluting coronary stents. The relative small number of patients enrolled in PECOPS I precludes to infer any further conclusions.

Randomized comparative trial of a thin‐strut bare metal cobalt‐chromium stent versus a sirolimus‐eluting stent for coronary revascularization

To see whether use of a sirolimus-eluting stent (SES) is superior to a third-generation thin-strut, cobalt-chromium stent (CCS) in terms of in-segment late loss at 9 months in patients with symptomatic coronary artery disease. Stent-strut thickness has been shown to be strictly related with risk of in-stent restenosis, but available demonstrations of the angiographic efficacy of SES have been based on comparisons with thick-strut bare metal control stents. The primary outcome measure of this single-center, single-blind randomized comparative trial was 9-month in-segment late loss. Eligibility criteria were symptomatic coronary artery disease and target vessel diameter appropriate for implantation a 3-mm stent. Based on a power calculation, 104 patients were randomly assigned to receive a SES (Cypher) or a CCS (Vision). In-segment late loss was significantly lower in the SES group (0.18 +/- 0.40 mm vs 0.58 +/- 0.51 mm, P < 0.001). Regarding subsidiary outcome measures, in-segment restenosis (at 9 months) was recorded in 10% (5/50) patients treated with SES and 23% (11/48) receiving CCS (P = 0.14). No clinical difference between the two groups was apparent at 12 months. Freedom from target vessel failure at 12 months was 72% for SES patients and 68% for CCS patients (P = 0.65). In patients with de-novo coronary lesions at medium risk of restenosis the anti-proliferative effect of SES is greater than that of a thin-strut CCS. Nevertheless, the angiographic results of the CCS were rather good. It remains to be seen whether the angiographic superiority of SES can translate into clinical superiority.

822-3 Sirolimus-eluting stents for failed brachytherapy: Results from the SECURE registry

Jorg Hausleiter, Adnan Kastrati, Julinda Mehilli, Helmut Schuhlen, Franz Dotzer, Christoph Goos, Gisela Pogatsa-Murray, Michael Vogeser, Martin Breuer, Josef Dirschinger, Albert Schomig, The OSIRIS Study Group, German Heart Center Munich, Munich, Germany, 1. Medizinische Klinik, Klinikum rechts der Isar, Munich, GermanySirolimus coated stents are a promising new therapy for restenosis in de-novo coronarylesions. Except for the promising results achieved with brachytherapy, the treatment ofrecurrent in-stent-restenosis (ISR) remains a challenging clinical issue. Given the effi-cacy of systemic administration of Sirolimus to prevent neointimal hyperplasia in animalmodels and to halt and even reverse the progression of allograft vasculopathy, it seemsreasonable to consider this drug as a good option for oral treatment to prevent recurrentISR. This randomized, double-blind, placebo-controlled study is aimed at evaluating theefficacy of 2 different regimens of oral Sirolimus in patients with ISR treated with repeatPTCA. We enrolled 300 patients with ISR in native coronary arteries who were randomlyassigned to one of three treatment arms: usual-dose Sirolimus, high-dose Sirolimus andplacebo. All patients in the two treatment arms received Sirolimus loading two days priorto and the day of intervention followed by maintenance therapy for 7 days. The differencebetween usual- and high-dose arms was in the amount of pre-treatment, 8 mg in theusual-dose Sirolimus arm and 24 mg in the high-dose Sirolimus arm. The maintenancetherapy after intervention consisted of 2mg/d for 7 days in both arms. Angiographicbinary restenosis at 6-months angiography was the primary end point of the study. Sam-ple size was estimated to give sufficient power to the trial for detecting a 25 and 50%reduction of the binary restenosis with the two Sirolimus doses. Angiographic and 1-yearclinical follow-up is in progress and will be completed in January 2004. The final studyresults will be presented.

Sirolimus-Eluting Stents to Treat Lesions With a High Risk of Restenosis. Six-Month Clinical Follow-Up in the First 100 Patients

Sirolimus-eluting stents have been shown to be effective in de-novo coronary lesions, reducing restenosis strikingly in a subset of lesions with a low or moderate risk of restenosis. We decided to assess their usefulness in lesions with a high risk of restenosis. We included consecutive patients with lesions that met at least one of the following criteria: a) in-stent restenosis; b) diffuse lesion (>20 mm); c) small vessel (< or =2.5 mm), and d) total occlusion. Between June 2002 to December 2002, 100 patients were included (61 [11] years, 84% men, 21% with diabetes). In all, 154 lesions were treated (34% diffuse lesions, 36% in small vessels, 20% in-stent restenosis and 20% occlusions). An average of 1.6 (0.7) stents were implanted per patient. Mean diameter was 2.74 (0.26) mm, mean length was 21 (8.5) mm and total stent length per patient was 33 (16) mm. The acute success rate was 98%. After the procedure 2 (2%) non-Q-wave infarctions were diagnosed. No episodes of acute or subacute thrombosis occurred. During a follow-up period of 8.5 (2) months (range 6-12 months) there were two (2%) late thromboses, one of which caused an infarction. Target lesion revascularization was required in 3 patients (3%), two of whom were the patients with late thrombosis. Sirolimus-eluting stents can be used in lesions with a high risk of restenosis. The rate of thrombosis was low, and the use of these stents was associated with a strikingly low rate of target lesion revascularization during follow-up.

Long-term follow-up of incomplete stent apposition in patients who received sirolimus-eluting stent for de novo coronary lesions: an intravascular ultrasound analysis.

Incomplete stent apposition (ISA) has been previously documented after sirolimus-eluting stent (SES) implantation. The aim of this study was to investigate the long-term intravascular ultrasound (IVUS) findings of ISA in patients who received SES. A total of 13 patients who received SES and showed ISA at follow-up IVUS (follow-up I) were investigated. IVUS was performed on all of these patients 12 months later (follow-up II). Quantitative ISA area measurement was also performed at follow-up I and II. No vascular remodeling was observed in the vessel segment with ISA; external elastic membrane area was 19.4+/-6.6 versus 19.5+/-6.4 mm2 at follow-up I and II, respectively. There was also no significant change in external elastic membrane area between vessel segment with ISA and without ISA (+1.5% versus -3.0%, respectively; P=0.27) at late follow-up. The ISA area, either including (2.5+/-1.7 versus 3.8+/-6.3 mm2; P=NS) or excluding (2.5+/-1.8 versus 2.4+/-1.7 mm2; P=NS) a single patient with aneurysm formation, was not significantly different between follow-up I and II. One patient manifested a coronary aneurysm in the stented segment at late follow-up that was probably present at the initial follow-up but masked by thrombus. It was successfully treated with a covered stent. All patients were asymptomatic, and no patient experienced late thrombotic occlusion. Vessel dimensions and area of ISA did not change over time, except for 1 coronary aneurysm that became apparent. ISA after implantation of a SES was not associated with adverse events at late follow-up.

Clinical and angiographic effects of directional atherectomy in De Novo coronary artery lesions located at the ostium of the left anterior descending artery

Clinical and angiographic effects of directional atherectomy in De Novo coronary artery lesions located at the ostium of the left anterior descending artery

Oral rapamune to inhibit restenosis in patients with multi de-novo coronary lesions requiring stenting

Oral rapamune to inhibit restenosis in patients with multi de-novo coronary lesions requiring stenting

Sirolimus-eluting stent for treatment of complex in-stent restenosis: The first clinical experience

ObjectivesIn this study, we assess the value of sirolimus eluting stent (SES) implantation in patients with complex in-stent restenosis (ISR). BackgroundThe treatment of ISR remains a therapeutic challenge, since many pharmacological and mechanical approaches have shown disappointing results. The SESs have been reported to be effective in de-novo coronary lesions. MethodsSixteen patients with severe, recurrent ISR in a native coronary artery (average lesion length 18.4 mm) and objective evidence of ischemia were included. They received one or more 18 mm Bx VELOCITY SESs (Cordis Waterloo, Belgium). Quantitative angiographic and three-dimensional intravascular ultrasound (IVUS) follow-up was performed at four months, and clinical follow-up at nine months. ResultsThe SES implantation (n = 26) was successful in all 16 patients. Four patients had recurrent restenosis following brachytherapy, and three patients had totally occluded vessels preprocedure. At four months follow-up, one patient had died and three patients had angiographic evidence of restenosis (one in-stent and two in-lesion). In-stent late lumen loss averaged 0.21 mm and the volume obstruction of the stent by IVUS was 1.1%. At nine months clinical follow-up, three patients had experienced four major adverse cardiac events (two deaths and one acute myocardial infarction necessitating repeat target vessel angioplasty). ConclusionsThe SES implantation in patients with severe ISR lesions effectively prevents neointima formation and recurrent restenosis at four months angiographic follow-up.

Vascular remodeling in atherosclerotic coronary arteries is affected by plaque composition.

Narrowing of lumen in atherosclerotic lesions is determined not solely by accumulation of plaque but also by constrictive or expansive vascular remodeling. Underlying mechanisms and determinants of these bidirectional processes are not known. To elucidate the response of vascular remodeling to progressive atherosclerosis by analyzing its potential association with composition of plaque. Seventy patients with 77 de-novo coronary artery lesions underwent intravascular ultrasound imaging before coronary intervention. Target lesions were defined as soft, fibrous/mixed, and calcified plaques. Quantitative measurements of area of lumen (A(L)), total area of vessel (A(TV)) and area of plaque (A(P) = A(TV)-A(L)) were performed at the lesion site and at the proximal and distal reference sites. Remodeling was determined by using a remodeling index [I(R) = (stenosis of A(TV)/mean reference A(TV)) x 100]. Overall vascular remodeling was balanced with a mean remodeling index of 100.2+/-19.3% and a high interlesion range (60.2-152.4%). The remodeling index for soft lesions was significantly higher than those for fibrous/mixed and calcified lesions (110+/-18.8 versus 96.2+/-14.4 and 85.9+/-15.1%, P < 0.01). Calcified lesions exhibited lower remodeling indexes than did uncalcified lesions (85.9+/-15.1 versus 104.6+/-18.4%, P < 0.01). Processes involved in vascular remodeling are affected by composition of plaque insofar as there is a higher prevalence of constrictive remodeling among calcified plaques and a higher prevalence of expansive remodeling among soft lesions. These findings indicate that constrictive remodeling is a late manifestation in atherogenesis. Future studies are warranted in order to enhance the understanding of progression of atherosclerosis, and of mechanisms of vascular remodeling and their impacts on interventional therapy.

Successful Directional Atherectomy of de Novo Coronary Lesions Assessed With Three-dimensional Intravascular Ultrasound and Angiographic Follow-up

Successful Directional Atherectomy of de Novo Coronary Lesions Assessed With Three-dimensional Intravascular Ultrasound and Angiographic Follow-up

Successful directional atherectomy of de Novo coronary lesions assessed with three-dimensional intravascular ultrasound and angiographic follow-up

Successful directional atherectomy of de Novo coronary lesions assessed with three-dimensional intravascular ultrasound and angiographic follow-up

Successful Directional Atherectomy of De Novo Coronary Lesions Assessed With Three-Dimensional Intravascular Ultrasound and Angiographic Follow-Up

Recent histopathologic and intravascular ultrasound (IVUS) data indicate that inadequate compensatory enlargement of atherosclerotic lesions contributes to the development of significant arterial stenoses. Such lesions may contain less plaque, which may have implications for atheroablative interventions. In this study, we compared lesions with (group A, n = 16) and without inadequate compensatory enlargement (group B, n = 30) as determined by IVUS. The acute results and the follow-up lumen dimensions of angiographically successful directional coronary atherectomy procedures were compared. Inadequate compensatory enlargement was considered present when the preintervention arterial cross-sectional area at the target lesion site was smaller than that at the (distal) reference site. Three-dimensional IVUS analysis and quantitative angiography were performed in 46 patients before and after intervention. IVUS measurements included the arterial, lumen, and plaque (arterial minus lumen) cross-sectional areas at the target lesion site (i.e., smallest lumen site) and the (distal) reference site. Angiographic follow-up was performed in 42 patients. Preintervention and postintervention angiographic measurements and IVUS lumen cross-sectional area measurements were similar in both groups. However, at follow-up, the angiographic minimum lumen and reference diameters were significantly smaller in group A compared with group B (1.71 ± 0.47 mm vs 2.14 ± 0.73 mm, p <0.03, and 2.97 ± 0.29 mm vs 3.39 ± 0.76 mm, p <0.02; group A vs B). The data of this observational study suggest that lesions with inadequate compensatory enlargement, as determined by IVUS before intervention, may have less favorable long-term lumen dimensions after directional coronary atherectomy procedures.