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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.

Objective: We designed this prospective study to test the hypothesis that platelet antigen (PlA) polymorphism of glycoprotein (GP) IIIa is associated with an increased risk for adverse events after coronary stent placement., Background: Platelets play a central role in arterial thrombosis. The PlA polymorphism of GP IIIa, a constituent of the fibrinogen receptor, may influence the platelet function and, thereby, the early outcome of patients after coronary stent placement., Methods: The study included 1,759 consecutive patients with stable or unstable angina and successful coronary stent placement. Platelet antigen genotypes were determined by allele-specific restriction enzyme analysis. The end point of the study was a composite of death, myocardial infarction and urgent revascularization during the first 30 days after stent placement., Results: The PlA1 genotype of the patients included was: 70.2% were homozygous for platelet antigen 1 (PlA1), 2.6% homozygous for platelet antigen 2 (PlA1), and 27.2% were heterozygous (PlA1/A2). The incidence of the composite end point was 5.5% among PlA2 carriers and 5.4% in homozygous PlA1 subjects (p = 0.94). It was 5.4% in PlA1/A1 patients, 4.8% in PlA1/A2 patients and 13.0% in PlA2A2 patients (p = 0.06). The combined incidence of death or myocardial infarction was 4.3% in PlA1/A1 patients, 4.2% in PlA1/A2 patients and 13.0% in PlA2/A2 patients (p = 0.02)., Conclusions: The isolated presence of the PlA2 allele in heterozygous patients is not associated with any detectable increase in the risk for an adverse 30-day outcome after coronary stenting. This study suggests also that an increased risk is likely to be present in homozygous carriers of the PlA2 allele, but this should be confirmed in a much larger series of patients.

The glycoprotein complex Ia/IIa (GP Ia/IIa) is a major collagen receptor on platelets and other cell types. Recently, linked polymorphisms within the coding region of the GP Ia gene (C807T and G873A) were identified that are related to GP Ia/IIa surface expression. The T807/A873 allele is associated with high expression, whereas the C807/G873 allele is associated with low surface expression of GP Ia/IIa. Subsequently, the T807 allele was found to be associated with coronary and cerebral infarction in younger patients. Platelet adhesion to the vessel wall plays a pivotal role in thrombosis after coronary artery stent placement. The goal of this study was to test whether C807T polymorphism is associated with a higher incidence of thrombotic events following coronary stenting. Consecutive patients treated with coronary stent placement (n = 1797) were genotyped for C807T polymorphism with polymerase chain reaction and allele-specific fluorogenic probes. The composite end point was defined as death, myocardial infarction, or urgent target vessel revascularization within 30 days of stent implantation. The genotype distribution of the study population was CC in 36.5%, CT in 46.7%, and TT in 16.8% of the patients. The incidence of the composite end point was 6.5% in T allele carriers and 5.3% in noncarriers (odds ratio for T allele carriage 1.23 [95% confidence interval, 0.81-1.86], P =.33). After adjusting for other baseline characteristics, the odds ratio for the composite end point was 1.15 (0.76-1.75). Therefore, C807T genotype has no significant influence on the major adverse events occurring after coronary artery stenting.

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.

Platelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa) plays a fundamental role in atherothrombosis. The human platelet antigen (HPA) -1 and the HPA-3 are the most extensively studied polymorphisms of GPIIIa and GPIIb, respectively. This study was designed to test, in a large population, the hypothesis that these polymorphisms represent a risk factor for the occurrence of coronary artery disease (CAD) and myocardial infarction (MI). Consecutive, angiographically examined patients with significant coronary stenoses but without symptoms or signs of old or acute MI constituted the group with CAD (CAD, n = 998) and those with old or acute MI constituted the group with MI (MI, n = 793). As controls served subjects, matched with patients for age and sex, with neither angiographic CAD nor symptoms or signs of MI (matched controls [MC], n = 340) as well as a group of blood donors without cardiac symptoms or signs of CAD (BD, n = 104). Genotype distribution was similar across the groups; HPA-1a/a: HPA-1a/b: HPA-1b/b was 75.0%: 22.1%: 2.9% in BD, 72.6%: 24.7%: 2.6% in MC, 70.5%: 26.8%: 2.7% in CAD, and 70.7%: 26.4%: 2.9% in MI; HPA-3a/a: HPA-3a/b: HPA-3b/b was 39.4%: 40.4%: 20.2% in BD, 33.5%: 50.0%: 16.5% in MC, 35.0%: 46.4%: 17.0% in CAD, and 37.1%: 48.0%: 16.5% in MI. There was no interaction between these polymorphisms, nor between each of these polymorphisms and other risk factors. Thus, the HPA-1 and HPA-3 polymorphisms are neither separately nor in concert associated with any measurable increase of the risk for CAD or MI in angiographically evaluated subjects.

Objectives: In the Intracoronary Stenting and Antithrombotic Regimen-2 trial (ISAR-2), we sought to investigate the effect of abciximab on angiographic and clinical restenosis after stenting following acute myocardial infarction (AMI). We also intended to assess the impact of abciximab on clinical outcome in this setting., Background: It is unclear whether abciximab reduces neointima formation after stenting. Such an effect may be particularly prominent in thrombus-containing lesions., Methods: Patients undergoing stenting within 48 h after onset of AMI were randomly assigned to receive either standard-dose heparin or abciximab plus reduced-dose heparin. Of 401 patients randomized, 366 without 30-day adverse events were eligible for six-month angiographic follow-up. Scheduled angiography was performed in 80% of these patients., Results: By 30 days, the composite clinical end point of death, reinfarction, and target lesion revascularization (TLR) was reached in 5.0% of the abciximab group and in 10.5% of the control group (p = 0.038). At one year, absolute reduction in the composite clinical end point by abciximab was still 5.7% but had lost its statistical significance. Our primary end point, late lumen loss, was 1.26+/-0.85 mm with abciximab and 1.21+/-0.74 mm with standard heparin (p = 0.61), and binary angiographic restenosis rates were 31.1% and 30.6%, respectively (p = 0.92)., Conclusions: In patients undergoing stenting following AMI, abciximab exerted beneficial effects by substantially reducing the 30-day rate of major adverse cardiac events. During one-year follow-up, there was no additional benefit from a reduction in TLR nor did abciximab reduce angiographic restenosis.

C825T polymorphism in the G protein beta3 subunit gene (GNB3) has been associated with arterial hypertension, coronary artery disease and myocardial infarction. On the cellular level, C825T polymorphism is associated with altered transmembrane signaling via adenylyl cyclase inhibiting (G(i)) G proteins. This study was designed to test whether C825T polymorphism has an impact on the processes leading to restenosis and thrombosis following coronary stenting. The primary endpoint of the study was angiographic restenosis (> or =50% diameter stenosis) at 6-month follow-up. Secondary endpoint was angiographically proven stent thrombosis within 30 days of implantation. In the 562 consecutive patients C825T genotype was CC, 46.1%, CT, 45.2% and TT, 8.7%. The incidence of angiographic restenosis was 32.7% in homozygous carriers of the C allele, 28.2% in CT patients and 33.3% in homozygous carriers of the T allele (P = 0.563). C825T genotype distribution in 34 consecutive patients with subacute stent thrombosis (44.0% CC, 50.0% CT, and 6.0% TT) was not different from that of 451 patients with angiographically patent stented vessel (45.4% CC, 44.6% CT, 10.0% TT; P = 0.644). In conclusion, C825T polymorphism has no appreciable impact on the mechanisms leading to thrombosis and restenosis following coronary stent placement.

Both glycoprotein (GP) IIb and IIIa of platelet fibrinogen receptor are polymorphic proteins. Unlike GPIIIa, there is little information about the clinical significance of the GPIIb polymorphism. We designed this prospective study to assess whether patients with the human platelet antigen (HPA)-3 polymorphism of GPIIb are more susceptible to developing thrombosis and restenosis after coronary stent placement. We included 2,178 consecutive patients with coronary artery disease who underwent intracoronary stent implantation, 789 (36.2%) with HPA-3a/a, 1,023 (47.0%) with HPA-3a/b, and 366 (16.8%) with HPA-3b/b genotype. The incidence of stent thrombosis was 1.7% in HPA-3a/a, 1.7% in HPA-3a/b, and 1.6% in HPA-3b/b patients (p = 0.999). The incidence of stent restenosis was 37.3% in HPA-3a/a, 36.2% in HPA-3a/b, and 34.6% in HPA-3b/b patients (p = 0.724). Event-free survival 1 year after stent placement was 76.1% for HPA-3a/a, 76.5% for HPA-3a/b, and 76.4% for HPA-3b/b patients (p = 0.968). We conclude that the HPA-3 polymorphism of platelet GPIIb is not associated with an increase in the risk of thrombosis and restenosis over 1 year after coronary stent placement. These data indicate that unlike the HPA-1 polymorphism of GPIIIa, the HPA-3 polymorphism of GPIIb may not serve as a useful genetic marker for the risk assessment of patients treated with intracoronary stenting.

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.

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.

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.