Integrin ß1 polymorphisms and bleeding risk after coronary artery stenting.

Bleeding complications following percutaneous coronary intervention associate with increased mortality. However, the underlying molecular mechanisms are insufficiently understood. Platelet recruitment and activation at sites of vascular injury depends on the function of integrin adhesion receptors. Besides GPIIbIIIa as the most abundant integrin receptor, platelets relevantly express ß1 integrins. Experimental evidence from in vivo studies suggests a significant role of ß1 integrins in primary haemostasis. However, little is known about the clinical impact of genetic alterations of the ß1 subunit, which might contribute to bleeding complications in patients. In this study, we performed DNA sequencing of patients suffering from bleeding complications after coronary artery stenting according to TIMI or BARC classification. We isolated DNA samples from 741 patients out of a cohort from 14,160 patients recruited in seven randomized clinical trials between June 2000 and May 2011. Subsequently, Sanger sequencing was performed covering the ß1 integrin cytoplasmic activation domain (exon16) and its non-coding upstream region. Out of 764 patients suffering from bleeding complications, 741 DNA samples were successfully sequenced. Genotype variation was detected for SNP rs2153875 located within the non-coding upstream region with following allele frequency in study population: CC (7.3%), CA (35%) and AA (57.8%), which is similar to a general population cohort. Further, genotype variation in SNP rs2153875 do not associate with the frequency of TIMI or BARC classified access or non-access site bleedings. Genotype variations of the ß1 integrin activation domain do not associate with bleeding risk after PCI.

A comparison of gamma-glutamyl transferase and alkaline phosphatase as prognostic markers in patients with coronary heart disease.

BACKGROUND AND AIMS: Whether gamma-glutamyl transferase (GGT) or alkaline phosphatase (ALP) is a better prognostic marker in patients with coronary heart disease (CHD) remains unknown. The aim of this study was to compare the prognostic value of GGT and ALP in patients with CHD. METHODS AND RESULTS: This study included 3768 patients with CHD. The main study outcome was 3-year all-cause mortality. The median values of GGT and ALP were 36.2 U/L and 69.3 U/L. Patients were divided into subgroups according to GGT or ALP activity > or ≤median. Overall, there were 304 deaths: 195 deaths occurred in patients with GGT >median (n = 1882) and 109 deaths occurred in patients with GGT ≤median (n = 1886); Kaplan-Meier [KM] estimates of all-cause mortality were 11.9% and 6.4% (unadjusted hazard ratio [HR] = 1.85, 95% confidence interval [CI], 1.46 to 2.34]; P < 0.001). According to ALP activity, 186 deaths occurred in patients with ALP >median (n = 1883) and 118 deaths occurred in patients with ALP ≤median (n = 1885); KM estimates of all-cause mortality were 11.4% and 7.1% (unadjusted HR = 1.64 [1.30-2.06]; P < 0.001). After adjustment, GGT (adjusted HR = 1.32 [1.11-1.58]; P = 0.002) but not ALP (adjusted HR = 1.20 [1.00-1.43]; P = 0.051, with both HR calculated per 1 unit increment in logarithmic GGT or ALP scale) remained significantly associated with the risk for mortality. The C statistic of the mortality model with GGT was greater than the C statistic of the model with ALP (0.831 [0.802-0.859] vs. 0.826 [0.793-0.855]; P < 0.001). CONCLUSIONS: In patients with CHD, GGT was a stronger correlate of all-cause mortality than ALP.

Angiographic and clinical outcomes of patients treated with everolimus-eluting bioresorbable stents in routine clinical practice: Results of the ISAR-ABSORB registry.

OBJECTIVES: We aimed to analyze angiographic and clinical results of patients undergoing BRS implantation in a real-world setting. BACKGROUND: Angiographic and clinical outcome data from patients undergoing implantation of drug-eluting bioresorbable stents (BRS) in routine clinical practice is scant. METHODS: Consecutive patients undergoing implantation of everolimus-eluting BRS at two high-volume centers in Munich, Germany were enrolled. Data were collected prospectively. All patients were scheduled for angiographic surveillance 6-8 months after stent implantation. Quantitative coronary angiographic analysis was performed in a core laboratory. Clinical follow-up was performed to 12 months and events were adjudicated by independent assessors. RESULTS: A total of 419 patients were studied. Mean age was 66.6 ± 10.9 years, 31.5% had diabetes mellitus, 76.1% had multivessel disease, and 39.0% presented with acute coronary syndrome; 49.0% of lesions were AHA/ACC type B2/C, 13.1% had treatment of bifurcation lesions. Mean reference vessel diameter was 2.89 ± 0.46 mm. At angiographic follow-up in-stent late loss was 0.26 ± 0.51 mm, in-segment diameter stenosis was 27.5 ± 16.1, and binary angiographic restenosis was 7.5%. At 12 months, the rate of death, myocardial infarction, or target lesion revascularization was 13.1%. Definite stent thrombosis occurred in 2.6%. CONCLUSIONS: The use of everolimus-eluting BRS in routine clinical practice is associated with high antirestenotic efficacy in patients undergoing angiographic surveillance. Overall clinical outcomes at 12 months are satisfactory though stent thrombosis rates are not insignificant. Further study with longer term follow-up and larger numbers of treated patients is required before we can be sure of the role of these devices in clinical practice.

A gender-specific analysis of association between hyperuricaemia and cardiovascular events in patients with coronary artery disease.

BACKGROUND AND AIMS: Gender-related differences in the association between hyperuricaemia and cardiovascular events remain poorly understood. The objective of this study was to assess gender-related differences in the association between hyperuricaemia and cardiovascular events in patients with coronary artery disease (CAD). METHODS AND RESULTS: This study included 13,273 patients with CAD. Hyperuricaemia was defined as a plasma uric acid >7.0mgdl(-1) in men and >5.7mgdl(-1) in women. The primary outcome was 1-year all-cause mortality. Hyperuricaemia was found in 3745 men (36.5%) and 1562 women (50.3%); odds ratio (OR)=1.76, 95% confidence interval (CI) 1.62-1.91; P<0.001. Women with hyperuricaemia were older, had higher proportions of patients with diabetes and arterial hypertension and had reduced renal function and higher C-reactive protein levels compared with men with hyperuricaemia. One-year all-cause mortality was 9.3% (n=143) in women with hyperuricaemia versus 6.9% (n = 252) in men with hyperuricaemia (P=0.002). After adjustment in multivariable Cox proportional hazards model, uric acid predicted 1-year mortality with an adjusted hazard ratio (HR)=1.17, 95% CI (1.03-1.31), P=0.012 in men and HR=1.25, 95% CI (1.06-1.48), P=0.007 in women, for each standard deviation increase in the natural logarithm. Uric acid predicted 1-year mortality with an area under the receiver-operating characteristic curve=0.625, 95% CI (0.594-0.656) in men and 0.676, 95% CI (0.635-0.717) in women (P=0.044, for women versus men). CONCLUSION: Hyperuricaemia predicts an increased risk of 1-year mortality in both genders with a stronger association in women. Differences in cardiovascular risk profile may explain the stronger association between hyperuricaemia and cardiovascular events in women.

Restenosis in bare metal and drug-eluting stents: distinct mechanistic insights from histopathology and optical intravascular imaging.

An increasing body of evidence points to the existence of important differences in the processes of restenosis following drug-eluting stent (DES) as compared to bare metal stent implantation. Preclinical investigation and human autopsy studies have shown that the high efficacy of DES in comparison with bare metal stents in preventing restenosis is achieved at the collateral cost of a delay in healing of the stented arterial segment. Moreover bare metal stent restenosis is typically characterised by a homogeneous tissue rich in smooth muscle cells; whereas DES restenosis is more often hypocellular and proteoglycan-rich. In addition, in-stent neoatherosclerosis appears to have an accelerated course in DES. Angiographic surveillance studies show that while neointimal formation peaks six months after bare metal stenting, neointimal formation after DES therapy is temporally right shifted and remains a dynamic ongoing process (late luminal loss creep) even out to five years. The widespread availability of high resolution optical coherence tomography (OCT) is affording better understanding of the pathophysiology of in-stent restenosis. While bare metal stent restenosis is characterized by predominantly homogenous high-signal tissue echogenicity, layered pattern or heterogeneous tissue composition is more common in DES restenosis. Moreover, preliminary data suggests that tissue attenuation may increase in a time-dependent manner. Nevertheless, the paucity of direct histopathological correlation studies means that the tissue composition of these lesions remains speculative. Data from specifically designed imaging-pathology correlation studies in suitable preclinical models of restenosis and in autopsy specimens is eagerly awaited. Furthermore, although long-term longitudinal clinical follow-up is necessary to define the clinical relevance of optical imaging findings, the nature of restenosis as a disease entity means that its natural history is often altered by a mandate for repeat intervention directly following data acquisition.

P27 and P53 gene polymorphisms and restenosis following coronary implantation of drug-eluting stents.

OBJECTIVE: Drug-eluting stents (DES) have reduced restenosis rates compared with bare-metal stents. P27 and P53 play important roles in the signal transduction leading to neointimal growth inhibition and induction of apoptosis of smooth muscle cells due to rapamycin and paclitaxel. We hypothesized that genetic variants of P27 and P53 influence the development of restenosis and the clinical outcome of patients receiving DES. METHODS: Polymorphisms in the genes encoding for P27 and P53 were tested for their association with restenosis and major adverse cardiac events. P27 C-79T and P53 G72C polymorphism genotypes were determined in a series of 433 consecutive patients receiving DES. Follow-up angiography after 6 months was performed in 87% of the patients. Genotyping was performed with PCR-based methods. RESULTS: For patients with the respective P27 C-79T and P53 G72C genotypes, the angiographic restenosis rates were between 5.0 and 22.0%, and the clinical restenosis rates were between 0.0 and 16.3%, without significant differences for the studied genotypes (p > 0.19). There was no association of the studied genotypes with the 1-year incidences of death and myocardial infarction. CONCLUSION: This study could not demonstrate a clinically relevant role of P27 and P53 polymorphisms in the processes leading to in-stent restenosis.

Polymer coatings and delayed arterial healing following drug-eluting stent implantation.

The antirestenotic efficacy of drug-eluting stent (DES) technology is based on the local delivery and modulated release of cytotoxic drugs targeted at inhibition of neointimal hyperplasia. Control of drug-release kinetics is a critical component of device efficacy. To date this has been most effectively performed by stent coatings comprised of non-erodable (permanent) polymer which facilitate drug loading and delay elution of the active drug. In fact all 4 of the systems currently approved by the Food and Drug Administration (FDA) use a permanent polymer-based drug release system. Balancing the need for lipophilicity (to bind active drug) with hydrophilicity (which offers superior biocompatibility) is a key challenge in polymer technology. Delayed arterial healing (DAH) following DES implantation has been demonstrated in human autopsy studies and animal models and is implicated in late thrombotic occlusion and delayed loss of antirestenotic efficacy. It is characterised by 1) persistent fibrin deposition; 2) delayed endothelialization; 3) chronic inflammation; and 4) persistent platelet activation. Within segment heterogeneity in degree of healing is typical. Inflammatory response to polymer residue plays an important role and may be non-specific (monocyte-macrophage predominant) or hypersensitivity related. Failure of early preclinical models to sufficiently predict DAH in man was an important problem. Second generation DES attempt to address the issue of DAH by using thinner stent struts, lower drug load and more biocompatible polymer. At present the focus of development is towards biodegradable polymer coatings which offer the attractive prospect of controlled drug-release without the potential for late polymer-associated adverse effects. This review highlights the role of polymer coatings in determination of DES efficacy, summarises the preclinical and clinical evidence linking polymer coatings with DAH and evaluates the promise of third generation polymer-free and biodegradable polymer DES.

Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation.

OBJECTIVES: Optimal antithrombotic/anticoagulation therapy in patients on chronic oral anticoagulation (OAC) undergoing drug-eluting stent (DES) implantation is unknown. We investigated the efficacy and safety of two regimens of antithrombotic/anticoagulation therapy in patients who present for DES implantation whilst on OAC. METHODS: We included a series of 515 patients on OAC who underwent DES implantation between 2002 and 2007. Based on predefined clinical and echocardiographic criteria, 306 patients continued OAC (triple therapy) and 209 patients discontinued OAC (dual therapy) for the time they received antiplatelet therapy with clopidogrel and aspirin [stent-related antithrombotic treatment (SRAT)]. The primary end point was a composite of death, myocardial infarction, stent thrombosis or stroke. RESULTS: During SRAT the primary endpoint was observed in 13 patients in the group with triple therapy versus 15 patients in the group with dual therapy [Kaplan-Meier estimates 4.2% and 7.2%, odds ratio (OR) = 0.61, 95% confidence interval (CI) 0.29-1.28; P = 0.19]. At 2 years of follow-up, the primary endpoint was observed in 35 patients in the group with triple therapy versus 36 patients in the group with dual therapy (Kaplan-Meier estimates 14.1% and 18.0%, OR = 0.76, 95% CI: 0.48-1.21; P = 0.25). Two-year incidence of major bleeding was 1.4% (n = 4, triple therapy) versus 3.1% (n = 6, dual therapy) (P = 0.34). CONCLUSIONS: In patients on chronic OAC undergoing DES implantation, clinical and echocardiographic criteria help to define postprocedural antithrombotic/anticoagulation therapy. Based on these criteria, both a double antiplatelet therapy (clopidogrel plus aspirin) and a triple therapy (OAC plus clopidogrel plus aspirin) are associated with favourable safety and efficacy.

Myeloperoxidase level in patients with stable coronary artery disease and acute coronary syndromes.

BACKGROUND: No studies have measured plasma myeloperoxidase (MPO) across the entire spectrum of patients with coronary artery disease (CAD). The aim of the study was to compare MPO level across the entire spectrum of CAD, to assess the accuracy of MPO in predicting acute coronary syndromes and to define independent correlates of MPO level. DESIGN: This case-control study included 874 patients with angiographically proven CAD. Cases included 680 patients with CAD (382 patients with stable CAD, 107 patients with non-ST-segment elevation acute coronary syndromes and 191 patients with ST-segment elevation acute myocardial infarction). Controls included 194 subjects with normal coronary angiograms. MPO was measured using an enzyme immunoassay before angiography and heparin administration. RESULTS: MPO level [median (25th-75th percentiles)] was 74.5 (52.5-135.3) microg L(-1) in cases vs. 61.2 (44.6-80.9), microg L(-1) in controls (P < 0.001). MPO level was 61.2 (47.5-85.8), microg L(-1) in patients with stable CAD, 99.2 (62.2-154.9), microg L(-1) in patients with non-ST-segment elevation acute coronary syndromes and 129.5 (72.2-216.0) microg L(-1) in patients with acute myocardial infarction (P < 0.001). Elevated MPO level was associated with acute coronary syndromes with an area under receiver operating characteristic (ROC) curve of 0.731 (95% confidence interval 0.692-0.770; P < 0.001). Independent correlates of MPO level were acute coronary syndrome (P < 0.001), high-sensitivity C-reactive protein (P = 0.007), creatinine (P = 0.026), left ventricular ejection fraction (P = 0.027, negative association) and smoking (P = 0.028). CONCLUSIONS: MPO level is elevated in patients with CAD and higher levels of MPO were found with progression of CAD from stable CAD to non-ST-segment elevation acute coronary syndromes and to acute myocardial infarction.

Multivessel percutaneous coronary intervention: a review of the literature and fallacies in its interpretation.

Since its inception in the 1960s, coronary revascularization has established itself as a fundamental therapy for treating the acute and chronic manifestations of atherosclerotic coronary disease. Catheter-based techniques were realized in the late 1970s and have evolved from balloon dilatation of simple, discrete stenoses to complex, multivessel interventions across the spectrum of coronary disease presentations. In retrospect, there were two defining technological developments the introduction of coronary stenting which enabled more stable acute outcomes and the evolution of drug-eluting stents which ameliorated the effect of neointimal hyperplasia the dominant cause of delayed loss of efficacy. The role of catheter-based intervention in multivessel disease is well established in the treatment of ST-elevation myocardial infarction and acute coronary syndromes. On the contrary, in the arena of in stable coronary disease, its utility is keenly debated. The pace of development in cardiovascular pharmacology has rendered early investigation of best treatment strategies largely obsolete, while newer revascularization techniques have successfully extended the remit of catheter-based multivessel intervention strategies to include left main stem disease, bifurcation stenosis and chronic occlusions. Consequently complete revascularization is now available via a percutaneous approach and conventional beliefs relating to choice of revascularization strategy deserve re-assessment. The authors present a contemporary review of the literature and a challenge against fallacies in its interpretation.

Clinical evidence on polymer-based sirolimus and paclitaxel eluting stents.

Percutaneous coronary interventions with the use of stents have become the mainstay treatment of patients with various clinical manifestations of coronary artery disease. Despite their remarkable success, restenosis has remained the major drawback and its prevention has absorbed intensive experimental and clinical research work. After the failure of multiple efforts with systemic use of various drugs, local application of antiproliferative and anti-inflammatory agents released by specially designed coated stents led to considerable suppression of neointima and opened new prospects in the prevention of restenosis. An increasing body of evidence is showing the advantages provided by drug-eluting stents (DES) in almost all subsets of patients with coronary artery disease with a drastic decrease in the need for reintervention. To date, the most commonly used and the only US Food and Drug Administration (FDA) approved DES are a sirolimus-eluting stent (Cypher) and a paclitaxel-eluting stent (Taxus), both of which are polymer-based DES and will constitute the focus of this review. Recent data demonstrate that DES are not equal in their safety and efficacy. A less optimistic aspect of DES technology are the reiterated concerns about a more prolonged risk of stent thrombosis. Although all agree on the need of a longer duration of dual antiplatelet therapy in patients treated with DES, its optimal length is still to be defined. Because polymers used for stent coating are often seen at the origin of the compromised long-term safety of DES, new technologies able to avoid permanent polymers may offer a valuable alternative.

Current drug-eluting stents in complex patients and lesions.

Drug-eluting stents (DES) are playing an increasingly important role in the treatment of coronary artery disease. These new devices work by releasing controlled amounts of pharmacological agents with anti-restenosis properties at the implantation site. Most of them use polymer coating as a drug carrier, but concerns about long-term negative effects of a permanent polymer coating have stimulated the development of non-polymer DES or DES based on bioabsorbable polymers. Several randomized studies with DES have demonstrated their superiority over bare metal stents mostly in selected patients and lesion subsets. Accumulating evidence is showing significant differences in performance between currently used DES. These differences are more pronounced in complex, high-risk subsets of patients and lesions and should be considered during the process of DES selection for the individual patient. Interventional cardiologists have learned that patients who receive DES require a more prolonged antiplatelet therapy, but the optimal length and regimen are still unclear and further investigations are needed. Major advances in interventional cardiology have caused a dramatic shift away from aorto-coronary bypass surgery and an increase in the complexity of percutaneous coronary interventions. Observational and specifically designed randomized studies are currently addressing the issue of the role of DES in complex situations including in-stent restenosis, ostial and bifurcation lesions, chronic occlusions, small vessels, long lesions, saphenous vein grafts, multivessel disease, left main disease, acute myocardial infarction and diabetes mellitus. Although definitive answers are still to come from ongoing research, available data support the use of DES in most of these situations.

A randomized trial comparing stenting with balloon angioplasty in small vessels in patients with symptomatic coronary artery disease. ISAR-SMART Study Investigators. Intracoronary Stenting or Angioplasty for Restenosis Reduction in Small Arteries.

BACKGROUND: More than 30% of the lesions currently treated with interventional approaches are situated in vessels smaller in size than those representing an established indication for stenting. The objective of this randomized trial was to assess whether compared with PTCA, stenting of small coronary vessels is associated with a reduction of restenosis. METHODS AND RESULTS: Patients with symptomatic coronary artery disease with lesions situated in native coronary vessels between 2 and 2.8 mm in size were randomly assigned to be treated with either stenting (n=204) or PTCA (n=200). Adjunct therapy consisted of abciximab, ticlopidine, and aspirin. Repeat angiography at 6-month follow-up was performed in 83% of the patients. The primary end point of the study was the incidence of angiographic restenosis (>/=50% diameter stenosis) at follow-up; adverse clinical events, such as death, myocardial infarction, stroke, or target vessel revascularization, were assessed as secondary end points. After 7 months, there were no significant differences in the infarct-free survival rates between the 2 study groups: 96.6% for stent patients, and 97.0% for PTCA patients (P:=0. 80). Target vessel revascularization was needed in 20.1% of the stent patients and 16.5% of the PTCA patients (P:=0.35). The primary end point of angiographic restenosis was found in 35.7% of the stent patients and 37.4% of the PTCA patients (P:=0.74). The net lumen gain observed at follow-up was identical (0.76+/-0.78 in the stent group versus 0.76+/-0.63 mm in the PTCA group, P:=0.93). CONCLUSIONS: Stenting and PTCA are associated with equally favorable results when used for treating lesions in small coronary vessels.

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene is not associated with restenosis after coronary stent placement.

BACKGROUND: The renin-angiotensin system is thought to play a role in coronary thrombosis and restenosis. Plasma angiotensin I-converting enzyme (ACE) activity is associated with an insertion/deletion polymorphism in the gene coding for ACE. The objective of this study was to test the hypothesis that the D allele of the ACE gene is associated with a higher risk for restenosis after coronary stent placement. METHODS AND RESULTS: This prospective study included 1850 consecutive patients with coronary artery disease who underwent intracoronary stent implantation. The adverse clinical events recorded were death, myocardial infarction, and target vessel revascularization. The primary end point of the study was restenosis (>/=50% diameter stenosis at follow-up angiography performed in 84% of the patients). The secondary end point was clinical outcome 1 year after the procedure. The restenosis rate at the 6-month angiographic follow-up was 32.8% in patients with the II genotype, 34.0% for patients with the ID genotype, and 31.2% for patients with the DD genotype (P=0.62). One-year event-free survival was 77.7% in patients with genotype II, 75.2% in patients with genotype ID, and 75.5% in patients with genotype DD (P=0.54). The lack of association was also present in the subgroup of patients with a low risk for restenosis: the restenosis rate was 21.7% in II carriers, 23.4% in ID carriers, and 19.7% in DD carriers (P=0.83). CONCLUSIONS: The ACE DD genotype or D allele does not influence the 1-year clinical and angiographic outcome of patients undergoing coronary stent placement. These data suggest that routine determination of the ACE genotype may not help identify patients who are at a higher risk of thrombotic and restenotic events after coronary stent placement.

Prognostic value of the modified american college of Cardiology/American heart association stenosis morphology classification for long-term angiographic and clinical outcome after coronary stent placement.

Background-The modified American College of Cardiology/American Heart Association (ACC/AHA) lesion morphology criteria are predictive of early outcome after various coronary catheter interventions. Their potential prognostic value after stent implantation and, in particular, for restenosis and long-term clinical outcome has not been studied. We assessed the prognostic value of the modified ACC/AHA criteria for the long-term angiographic and clinical outcome of patients after coronary stenting. Methods and Results-This study includes 2944 consecutive patients with symptomatic coronary artery disease treated with coronary stent placement. Modified ACC/AHA lesion morphology criteria were used to qualitatively assess the angiograms; type A and B1 lesions were categorized as simple, and type B2 and C lesions were designated complex. Primary end points were angiographic restenosis and 1-year event-free survival. Restenosis rate was 33.2% in complex lesions and 24.9% in simple lesions (P<0.001). It was 21. 7% for type A, 26.3% for type B1, 33.7% for type B2, and 32.6% for type C lesions. One-year event-free survival was 75.6% for patients with complex lesions and 81.1% for patients with simple lesions (P<0. 001). It was 85.2% for patients with type A, 79.4% for type B1, 75. 9% for type B2, and 75.2% type C lesions. The higher risk for restenosis and an adverse outcome associated with complex lesions was also maintained after multivariate adjustment for other clinical and angiographic characteristics. Conclusions-The modified ACC/AHA lesion morphology scheme has significant prognostic value for the outcome of patients after coronary stent placement. Lesion morphology is able to influence the restenosis process and thus the entire 1-year clinical course of these patients.

Increased risk of restenosis after placement of gold-coated stents: results of a randomized trial comparing gold-coated with uncoated steel stents in patients with coronary artery disease.

BACKGROUND: Gold is a highly biocompatible material. Experimental evidence suggests that coating the stent with a gold layer may have a beneficial influence. In this randomized trial, we assessed whether gold-coated stents were associated with a better clinical and angiographic outcome after coronary placement. METHODS AND RESULTS: Patients with symptomatic coronary artery disease were randomly assigned to receive either a gold-coated Inflow stent (n = 367) or an uncoated Inflow stainless steel stent (n = 364) of identical design. Follow-up angiography was routinely performed at 6 months. The primary end point of the study was the occurrence of any adverse clinical event (death, myocardial infarction, or target-vessel revascularization) during the first year after stenting. At 30 days, there was no significant difference in the combined incidence of adverse events, with 7.9% in the gold-stent group versus 5.8% in the steel-stent group (P = 0.25). The incidence of angiographic restenosis (> or =50% diameter stenosis) was 49.7% in the gold-stent group and 38.1% in the steel-stent group (P = 0.003). One-year survival free of myocardial infarction was 88.6% in the gold-stent group and 91.8% in the steel-stent group (P = 0.14). One-year event-free survival was significantly less favorable in the gold-stent group (62.9% versus 73.9% in the steel-stent group; P = 0.001). CONCLUSIONS: Coating steel stents with gold had no significant influence on the thrombotic events observed during the first 30 days after the intervention. However, gold-coated stents were associated with a considerable increase in the risk of restenosis over the first year after stenting.

Influence of balloon pressure during stent placement in native coronary arteries on early and late angiographic and clinical outcome: A randomized evaluation of high-pressure inflation.

BACKGROUND: High-pressure dilatation is considered a better stent placement strategy, but this has not yet been proved by appropriately designed studies. The objective of this randomized trial was to assess the role of high-pressure dilatation in the early and late outcome of patients undergoing coronary stent placement. METHODS AND RESULTS: Consecutive patients with coronary stent placement were randomly assigned to high- (15 to 20 atm, 468 patients) or low- (8 to 13 atm, 466 patients) balloon-pressure dilatation. The primary end point of the study was the event-free survival at 1 year. Secondary end points were the incidence of stent thrombosis at 30 days and angiographic restenosis (>/=50% diameter stenosis) at 6 months. The incidence of stent thrombosis was 1.7% in the high-pressure and 1.9% in the low-pressure group (relative risk 0.89; 95% CI 0.30 to 2.56). During the first 30 days, although there was no significant difference in the incidence of Q-wave myocardial infarction, the incidence of non-Q-wave infarction was 6.4% in the high-pressure and 3.4% in the low-pressure group (relative risk 1. 87; 95% CI 1.02 to 3.42). The restenosis rate was 30.4% in the high-pressure and 31.4% in the low-pressure group (relative risk 0. 97; 95% CI 0.75 to 1.26). Event-free survival at 1 year was not significantly different between the groups, with 78.8% in high-pressure patients and 75.5% in patients assigned to low-pressure dilatation (hazard ratio 0.85; 95% CI 0.65 to 1.11). CONCLUSIONS: The systematic use of high-balloon-pressure inflation (15 to 20 atm) during coronary stent placement is not associated with any significant influence on the 1-year outcome of patients undergoing this intervention.

Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO) trial.

BACKGROUND: Increased thrombogenicity and smooth muscle cell proliferative response induced by the metal struts compromise the advantages of coronary stenting. The objective of this randomized, multicenter study was to assess whether a reduced strut thickness of coronary stents is associated with improved follow-up angiographic and clinical results. METHODS AND RESULTS: A total of 651 patients with coronary lesions situated in native vessels >2.8 mm in diameter were randomly assigned to receive 1 of 2 commercially available stents of comparable design but different thickness: 326 patients to the thin-strut stent (strut thickness of 50 microm) and 325 patients to the thick-strut stent (strut thickness of 140 microm). The primary end point was the angiographic restenosis (>/=50% diameter stenosis at follow-up angiography). Secondary end points were the incidence of reinterventions due to restenosis-induced ischemia and the combined rate of death and myocardial infarctions at 1 year. The incidence of angiographic restenosis was 15.0% in the thin-strut group and 25.8% in the thick-strut group (relative risk, 0.58; 95% CI, 0.39 to 0.87; P=0.003). Clinical restenosis was also significantly reduced, with a reintervention rate of 8.6% among thin-strut patients and 13.8% among thick-strut patients (relative risk, 0.62; 95% CI, 0.39 to 0.99; P=0.03). No difference was observed in the combined 1-year rate of death and myocardial infarction. CONCLUSIONS: The use of a thinner-strut device is associated with a significant reduction of angiographic and clinical restenosis after coronary artery stenting. These findings may have relevant implications for the currently most widely used percutaneous coronary intervention.

Previous cytomegalovirus infection and restenosis after coronary stent placement.

BACKGROUND: Reactivated cytomegalovirus may promote neointima formation after percutaneous coronary interventions by facilitating cell cycle progression through inhibition of the eukariotic tumor suppressor protein p53. This prospective study sought to investigate the effect of previous cytomegalovirus infection on restenosis after coronary stenting. METHODS AND RESULTS: In 551 consecutive patients with successful stent placement, we determined cytomegalovirus IgG titers. Primary and secondary end points were the rate of angiographic restenosis at 6 months and the rate of target vessel reintervention at 1 year, respectively. Three hundred forty patients (62%) had a positive cytomegalovirus IgG titer. We obtained angiographic follow-up in 82% of all patients. Angiographic restenosis rate was 28.7% in patients with positive cytomegalovirus titers and 34.6% in patients with negative titers (P=0.18). Between the groups with and without positive cytomegalovirus titers, there were no significant differences in late lumen loss (1.16+/-0.90 mm and 1.23+/-0.86 mm, respectively, P=0.44). Target vessel reintervention was performed in 16.8% of the patients with positive cytomegalovirus titers and in 17.5% of those without (P=0.82). Even after correction for potential confounding variables by multivariate analysis, positive cytomegalovirus titers did not manifest as a predictor of angiographic restenosis (adjusted odds ratio [95% confidence interval], 0.78 [0.52 to 1.19]). CONCLUSIONS: Previous cytomegalovirus infection does not carry an increased risk of restenosis after stenting.

PlA polymorphism of platelet glycoprotein IIIa and risk of restenosis after coronary stent placement.

BACKGROUND: Platelets play a central role in the process of restenosis after percutaneous coronary interventions. A polymorphism of platelet glycoprotein IIIa (PlA) has been associated with a higher risk of coronary thrombosis. We designed this prospective study to test the hypothesis that PlA polymorphism of glycoprotein IIIa is associated with an increased risk for restenosis after coronary stent placement. METHODS AND RESULTS: The study included 1150 consecutive patients with successful coronary stent placement and 6-month follow-up with coronary angiography. The end point of the study was the incidence of angiographic restenosis (>/=50% diameter stenosis) at follow-up. Of the 1150 patients, 72.5% were homozygous for PlA1, 24.7% were heterozygous (PlA1/A2), and 2.8% were homozygous for PlA2. Patients with the PlA2 allele demonstrated a significantly higher restenosis rate than did those without (47% versus 38%; OR, 1.42; 95% CI, 1.09 to 1.84). The risk was highest in homozygous carriers of PlA2 (53.1% restenosis rate). After adjustment for several clinical and angiographic characteristics, the presence of the PlA2 allele remained a significantly independent risk factor for restenosis (adjusted OR, 1.35; 95% CI, 1.07 to 1.70). The influence of the PlA2 allele on restenosis was stronger in women. Women with PlA2 had a restenosis rate of 52% compared with the 33% incidence among women homozygous for PlA1 (OR, 2.21; 95% CI, 1.27 to 3.85). CONCLUSIONS: This study showed a significant association between the PlA polymorphism of glycoprotein IIIa and the risk of restenosis after coronary stent placement. The risk was more pronounced in patients homozygous for PlA2 allele and in female patients.