Serum levels of circulating adhesion molecules after coronary angioplasty.

The activation of platelets, leukocytes, and vascular endothelial cells mediated by cell adhesion molecules may play a role in the mechanism of restenosis, which is still a significant complication after coronary angioplasty. We observed serial changes in the circulating soluble forms of adhesion molecules in 25 patients with coronary artery disease who underwent coronary angioplasty for a single lesion of the left anterior descending artery. Serum levels of sICAM-1 (p < 0.05) and sP-selectin (p < 0.05) were significantly increased immediately after angioplasty in the coronary sinus blood samples. These increases continued during the 48-hour observation period, and the maximum increase was seen 48 h after angioplasty for sICAM-1 (p < 0.01) and 24 h after angioplasty for sP-selectin (p < 0. 01). The level of sL-selectin increased 24 h (p < 0.01) and 48 h (p < 0.001) after angioplasty. These changes were not observed in the peripheral blood samples. The sE-selectin level did not change after angioplasty. A multiple regression analysis showed that the late loss index obtained from quantitative angiographic (QCA) analysis was correlated with the changes in sICAM-1 (r = 0.31, p < 0.05), sL-selectin (r = 0.28, p < 0.05), and sP-selectin (r = 0.26, p < 0. 05) 48 h after angioplasty in the coronary sinus blood samples, but was not correlated with procedural variables, other QCA variables, or the change in the sL-selectin level. The measurements of these adhesion molecule levels may help to evaluate traumatic vessel wall injury and inflammation at the intervention site after coronary angioplasty.     

Etanercept in the treatment of active refractory Crohn's disease: a single-center pilot trial

OBJECTIVES: Etanercept, an injectable tumor necrosis factor (TNF) receptor fusion protein, binds and inactivates human TNF and is used in active rheumatoid arthritis. Blocking TNF with monoclonal antibodies has also been beneficial in Crohn's disease. We attempted to determine the efficacy and safety of etanercept for induction of clinical, endoscopic, and histological improvement in patients with moderate to severe Crohn's disease despite standard treatment. METHODS: Ten patients with active Crohn's disease were treated with etanercept (25 mg s.c.) twice per week for 12 wk. Background therapy was kept stable during the trial. Crohn's disease activity index (CDAI), Inflammatory Bowel Disease Questionnaire, and C-reactive protein levels were measured at weeks 0, 2, 4, 8, and 12. Colonoscopies were performed before and after therapy in responders; endoscopic biopsies were scored for inflammation. RESULTS: At week 2 after the start, a clinical response (deltaCDAI > or = 70) was observed in 6/10 patients (median = 305 [294-418] to 166 [107-392]), with reduction in serum C-reactive protein levels (median = 17.2 [6.8-67.2] to 9.1 [0.9-17.2] mg/dl). Colonoscopies showed a reduction in inflammatory lesions in the four patients who attained remission (CDAI < 150), whereas the inflammatory score of the biopsies did not decrease significantly. No moderate or severe adverse events were observed. CONCLUSIONS: Etanercept may be effective in Crohn's disease refractory to standard therapy.     

A randomized, placebo-controlled trial of enoxaparin after high-risk coronary stenting: the ATLAST trial.

OBJECTIVES: We performed a multicenter, double-blind placebo-controlled trial to examine the efficacy and safety of enoxaparin in patients at high risk for stent thrombosis (ST). BACKGROUND: The optimal antithrombotic regimen for such patients is unknown. METHODS: We randomized 1,102 patients with clinical, angiographic or ultrasonographic features associated with an increased risk of ST to receive either twice-daily injections of weight-adjusted enoxaparin or placebo for 14 days after stenting. All patients received aspirin and ticlopidine. The primary end point was a 30-day composite end point of death, myocardial infarction (MI) or urgent revascularization. RESULTS: The target enrollment for the study was 2,000 patients. However, the trial was terminated prematurely at 1,102 patients after interim analysis revealed an unexpectedly low event rate. The primary outcome occurred in 1.8% enoxaparin-treated patients versus 2.7% treated with placebo (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.29 to 1.5, p = 0.30); for death or MI the rates were 0.9% vs. 2.2%, respectively (OR 0.41, 95% CI 0.14 to 1.2, p =0.13); and for MI, 0.4% vs. 1.6%, respectively (OR 0.22, 95% CI 0.05 to 0.99, p = 0.04). The groups had comparable rates of major bleeding (3.3% for enoxaparin, 1.6% for placebo, p =0.08), but minor nuisance bleeding was increased with enoxaparin (25% vs. 5.1%, p < 0.001). CONCLUSIONS: The clinical outcomes of patients at increased risk of ST are more favorable than previously reported, rendering routine oral antiplatelet therapy adequate for most. However, given its relative safety and potential to reduce the risk of subsequent infarction, a 14-day course of enoxaparin may be considered for carefully selected patients.     

Acute pleuropericarditis after coronary stenting: a case report.

A case of acute pleuropericarditis, which occurred after apparently successful percutaneous coronary intervention (PCI) for chronic total occlusion of the right coronary artery, is reported. The patient underwent coronary stenting without any immediate signs of complications. However, he had an acute onset of chest pain with fever which happened 4 h after PCI. He was diagnosed with acute pleuropericarditis by blood tests, electrocardiogram, chest X-ray, and echocardiogram. He rapidly recovered by intravenous hydrocortisone followed by oral prednisone administrations and percutaneous catheter pericardial drainage. Acute pleuropericarditis relevant to post-cardiac injury syndrome with an atypically early onset might have occurred in this case as a rare complication of PCI.     

Effect of cilostazol on restenosis after coronary angioplasty and stenting in comparison to conventional coronary artery stenting with ticlopidine

BACKGROUND: The role of antiplatelet therapy with ticlopidine plus aspirin in the prevention of subacute thrombosis after coronary artery stenting has been established. However, restenosis remains a major limitation in coronary artery stenting. METHODS: To compare the effect of cilostazol on restenosis after coronary angioplasty and stenting with that of ticlopidine after coronary artery stenting, 213 patients with 230 lesions who underwent successful coronary interventions were evaluated. Optimal results (residual stenosis less than 30%) were obtained by balloon angioplasty in 112 lesions, 64 lesions were treated with aspirin 81 mg/day (balloon-aspirin group) and 48 lesions with cilostazol 200 mg/day and aspirin 81 mg/day (balloon-cilostazol group). Stent implantation was performed in the remaining 118 lesions; 55 lesions were treated with ticlopidine 200 mg/day and aspirin 243 mg/day (stent-ticlopidine group) and 63 lesions with cilostazol 200 mg/day and aspirin 81 mg/day (stent-cilostazol group). Concomitant medications were continued for 4 to 6 months of follow-up. RESULTS: No adverse events including acute occlusion and subacute thrombosis occurred in any groups. Although immediate gain and minimal lumen diameter immediately after angioplasty were significantly larger in stent groups than those in balloon groups, net gain at follow-up was significantly larger in cilostazol groups (1.54+/-0.83 mm in balloon-cilostazol group and 1.65+/-0.78 mm in stent-cilostazol group) than other groups (1.02+/-0.81 mm in balloon-aspirin group and 1.21+/-0.70 in stent-ticlopidine group) as a result of significantly lower late loss and loss index in cilostazol groups. The restenosis rate was significantly lower in cilostazol groups (12.5% in balloon-cilostazol group and 14.3% in stent-cilostazol group) than other groups (43.8% in balloon-aspirin group and 32.7% in stent-ticlopidine group). The rate of recurrent angina was significantly lower in cilostazol groups (4.3% in balloon-cilostazol group and 1.9% in stent-cilostazol group) than in other groups (17.5% in balloon-aspirin group and 14.0% in stent-ticlopidine groups). CONCLUSIONS: Both optimal balloon angioplasty with cilostazol and coronary artery stenting with cilostazol have a potential to reduce restenosis compared with optimal balloon angioplasty with aspirin or conventional coronary artery stenting with ticlopidine plus aspirin.     

血脂康对冠心病粘附分子表达的影响

目的 探讨动脉粥样硬化(AS)时血脂异常对单核细胞(MC)粘附分子表达及调脂干预对其产生的影响.方法 选择冠心病不稳定性心绞痛(UA)患者30例,并经血脂康调脂治疗3个月后随访,同时选取正常对照者30例,检测研究对象的TC、LDL-c、MC表面CD11a、CD11b和CD18阳性细胞百分率,观察其变化以及测定冠心病患者血脂康调脂治疗前后血清P-选择素、ICAM-1、Ox-LDL的水平,分析之间的相关性.结果 不稳定性心绞痛患者血清Ox-LDL水平明显增高,与血清P-选择素水平呈显著正相关关系;LDL与CD11a、CD18相关显著.经血脂康调脂治疗后,患者在血清TC、LDL-c水平下降的同时,血清P-选择素、ICAM-1、Ox-LDL水平也显著降低,提示通过血脂康调脂干预治疗,能够阻止不稳定性心绞痛患者冠状动脉粥样病变的炎症反应,改善血管内皮细胞功能,延缓冠状动脉粥样病变的进展.结论 血脂康抑制Ox-LDL诱导的粘附分子表达是其独立于调脂之外的另一抗AS作用.     

Clinical and economic outcomes of multivessel coronary stenting compared with bypass surgery: a single-center US experience

Background Randomized trials comparing multivessel stenting with coronary artery bypass surgery (CABG) have demonstrated similar rates of death and myocardial infarction but higher rates of repeat revascularization after stenting. The impact of these alternative strategies on overall medical care costs is uncertain, particularly within the US health care system. Methods We performed a retrospective, matched cohort study to compare the clinical and economic outcomes of multivessel stenting and bypass surgery. The stent group consisted of 100 consecutive patients who underwent stenting of ≥2 major native coronary arteries at our institution. The CABG group consisted of 200 patients who underwent nonemergent isolated bypass surgery during the same time frame, matched (2:1) for age, sex, ejection fraction, diabetes mellitus, and extent of coronary disease. Detailed clinical follow-up and resource utilization data were collected for a minimum of 2 years. Total costs were calculated by use of year 2000 unit prices. Results Over a median follow up period of 2.8 years, there were no significant differences in all-cause mortality rates (3.0% vs 3.0%), Q-wave myocardial infarction (5.1% vs 4.0%), or the composite of death or myocardial infarction (7.1% vs 7.0%) between the stent and CABG groups (P = not significant for all comparisons). However, at 2-year follow up, patients with stents were more likely to require ≥1 repeat revascularization procedure (32.0% vs 4.5%, P < .001). The initial cost of multivessel stenting was 43% less than the cost of CABG ($11,810 vs $20,574, P < .001) and remained 27% less ($17,634 vs $24,288, P = .005) at 2 years. Conclusions Multivessel stenting and CABG result in comparable risks of death and myocardial infarction. Despite a higher rate of repeat revascularization, multivessel stenting was significantly less costly than CABG through the first 2 years of follow-up. (Am Heart J 2003;145:334-42.)     

Effect of angiotensin-converting enzyme inhibition on restenosis after coronary stenting

The Plasma level of angiotensin-converting enzyme (ACE) has been identified as a major risk factor for restenosis after coronary stent implantation in selected patients; ACE inhibition may therefore contribute to prevent its occurrence. The effect of oral ACE inhibition at conventional doses was analyzed retrospectively in a series of 897 patients with ischemia who received >or=1 coronary stent on 998 lesions and underwent angiographic follow-up; no exclusion criteria were introduced in this analysis. The restenosis rate in 282 patients (31.4%) taking ACE inhibitors was 36.6% compared with 22.9% in 615 non-ACE-inhibited patients (p = 0.00001, odds ratio [OR] 1.94, 95% confidence interval [CI] 1.45 to 2.59), and the late loss in minimum lumen diameter was 1.25 +/- 0.8 versus 0.96 +/- 0.8 mm, respectively (p = 0.0001). During univariate analysis, a negative effect of the drug on restenosis was observed in all subgroups of patients (i.e., hypertensives, diabetics, women, and patients with previous myocardial infarction). Similar effects were observed independently of the ACE gene insertion/deletion polymorphism. During multivariate analysis, ACE inhibition was confirmed as an independent risk factor for restenosis (OR 1.84, 95% CI 1.35 to 2.51, p = 0.0001). Other predictors were the implantation of multiple stents (OR 2.41, 95% CI 1.60 to 3.64, p <0.0001), diabetes (OR 2.34, 95% CI 1.61 to 3.41, p <0.0001), and vessel reference diameter before angioplasty (OR 0.51, 95% CI 0.38 to 0.69, p <0.0001). Although unexplained and apparently contradictory, our data suggest that the use of conventional oral doses of ACE inhibitors in a "real-world" population who underwent coronary stent implantation increases the incidence of in-stent restenosis. Such a finding does not negate the known clinical benefits of ACE inhibitors, but it may deserve attention when a patient treated with ACE inhibitors becomes a candidate for stent implantation.     

Intracoronary stenting and angiographic results: Restenosis after direct stenting versus stenting with predilation in patients with symptomatic coronary artery disease (ISAR-DIRECT trial).

The objective of this randomized study was to assess whether direct stenting leads to less restenosis than does conventional stenting (CS) with predilation in clinical practice. We included 910 patients who were randomly assigned to undergo either direct stenting (DS; n = 456) or CS (n = 454). No significant difference was observed in the incidence of angiographic restenosis (primary endpoint): 23.6% for DS and 21.0% for CS (P = 0.41; relative risk = 1.1; 95% CI = 0.8-1.5). The incidence of target vessel revascularization was 17.3% among DS and 14.8% among CS patients (P = 0.29; relative risk = 1.2; 95% CI = 0.8-1.6). The combined incidence of death or myocardial infarction at one year was 9.0% in the DS group and 7.0% in the CS group (P = 0.28). In conclusion, direct stenting is not associated with any reduction of thrombotic and restenotic complications as compared to the conventional stenting.     

Effect of amlodipine on vascular responses after coronary stenting compared with an angiotensin-converting enzyme inhibitor.

BACKGROUND: Prevention of restenosis after coronary stenting is clinically important. We compared amlodipine and quinapril to determine which is more effective in preventing restenosis after stenting. METHODS AND RESULTS: Immediately after successful coronary stenting of 101 lesions in 63 consecutive patients, the patients were randomly divided into 2 groups: 32 patients with 48 lesions were administered amlodipine 5 mg/day (group A), and 31 patients with 53 lesions were administered quinapril 10 mg/day (group Q). Lesions were assessed by quantitative coronary angiography (QCA) before and immediately after stenting and in the follow-up phase. Intravascular ultrasound (IVUS) could only be performed on 20 lesions in group A and 16 lesions in group Q throughout the follow-up period. We analyzed each lesion at 5 sites. In the follow-up phase, the minimal lumen diameter in group A was significantly larger than that in group Q (1.88 +/- 0.64 mm vs 1.52 +/- 0.53 mm, p<0.01). In the follow-up phase, the neointimal area (stent area-lumen area) in group A was significantly smaller than that in group Q (1.9 +/- 0.5 mm2 vs 2.7 +/- 0.8 mm2 at the middle portion of stent, p<0.01). CONCLUSION: These QCA and IVUS findings suggest that amlodipine has beneficial effects in inhibiting neointimal hyperplasia in stented lesions compared with quinapril.     

80岁及以上老年人冠状动脉内支架术疗效和安全性的观察

目的　评价年龄因素对冠心病患者选择性冠状动脉 (冠脉 )内支架术疗效和安全性的影响。　方法　连续 5 0 2例冠心病患者行选择性冠脉内支架术 ,根据年龄分组 :80～ 87岁 48例 ,70～ 79岁 143例 ,60～ 69岁 169例 ,3 5～ 5 9岁 142例。比较 4组支架术成功率及随访结果。　结果　 4组支架术成功率分别为 97 9%、97 2 %、97 6%和 96 5 % ,并发症率为 6 3 %、9 8%、7 1%、2 1% ,差异无显著性 (均为P >0 0 5 )。随访 1～ 3 0个月 ,平均 (12 0± 4 8)个月 ,随访率为 92 3 %。 4组的心绞痛复发分别为 2 7 9%、41 4%、5 0 3 %和 48 4% ,80～ 87岁组心绞痛复发显著少于 60～ 69岁组和 3 5～ 5 9岁组(均为P <0 0 5 ) ,但硝酸酯药物停用率 (4 1 9%、3 4 6%、3 0 7%和 3 5 5 % )、再入院率 (2 7 9%、3 6 8%、3 0 7%和 3 4 7% )、心功能改善率 (5 5 8%、44 4%、48 4%和 5 7 3 % )、心脏事件发生率 (18 6%、2 1 1%、2 4 8%和 2 1 0 % )和病死率 (7 0 %、3 8%、2 6%和 1 6% )差异无显著性 (均为P >0 0 5 )。　结论　年龄因素对冠脉内支架术的疗效和安全性无显著影响 ,80岁以上患者选择性冠脉内支架术安全、成功率高 ,近期疗效好     

Effect of cilostazol on in-stent neointimal hyperplasia after coronary artery stenting: a quantative coronary angiography and volumetric intravascular ultrasound study.

BACKGROUND: This study was designed to investigate the efficacy of cilostazol on the prevention of in-stent neointimal hyperplasia as measured by both quantitative coronary angiography (CAG) and volumetric intravascular ultrasound (IVUS). METHODS AND RESULTS: Fifty-nine patients (39 men, age 62 years) undergoing elective coronary stenting were randomly assigned to receive aspirin plus clopidogrel or ticlopidine (Group I, n=28, 30 lesions) or aspirin plus clopidogrel or ticlopidine plus cilostazol (Group II, n=31, 35 lesions). CAG and IVUS were performed and repeated at 6 months to assess the primary endpoints of minimal luminal diameter (MLD) and in-stent neointimal hyperplasia volume. Follow-up CAG was performed on all patients and follow-up IVUS study was available for 50 lesions in 48 patients (24 lesions in Group I, 26 in Group II). There were no significant differences in the baseline angiographic data between the 2 groups. At 6 months follow-up, in-stent MLD was 1.90+/-0.76 mm in Group I and 2.41+/-0.85 mm in Group II (p=0.006). Volumetric IVUS at 6 months demonstrated that in-stent intimal hyperplasia volume per stent length was 2.2+/-1.4 mm3/mm in Group I and 1.0+/-0.5 mm3/mm in Group II (p=0.001). CONCLUSIONS: Triple antiplatelet therapy including cilostazol seems to be more effective at preventing in-stent neointimal hyperplasia than a dual antiplatelet regimen.     

Effect of recombinant growth hormone treatment on children with Crohn's disease and short stature: a pilot study

BACKGROUND: Growth failure frequently complicates Crohn's disease in childhood. Abnormalities in the growth hormone (GH)/insulin-like growth factor-1 axis may occur. The effects of administered GH on growth have not been studied previously in a randomized trial. METHODS: Seven children (6 boys and 1 girl; age, 11.9-16 yr) with Crohn's disease and growth failure were enrolled. In phase 1, patients were randomized to either GH (0.05 mg/kg per day) or placebo; in phase 2, patients who received placebo during the first year received GH for various time periods. Follow-up was every 3 months for up to 2 years. RESULTS: During placebo treatment (4 patients), mean height-for-age z score (haz) increased 0.23 in the first half year and 0.55 in the second half year. The mean improvement in haz during the first half year of GH treatment (7 patients) was 0.13; during the second half year (5 patients), haz decreased 0.01. Effects of GH varied among patients; 2 patients grew only when nutritional supplementation was added. Observed changes were not statistically significant; however, the number of patients studied was small, and statistical analyses could have been affected by sample size. Serum insulin-like growth factor-1 levels correlated with height velocity. Only 2 patients later reached expected adult height. CONCLUSIONS: In this pilot study, GH treatment at the dose given did not stimulate growth in children with Crohn's disease and short stature. Whether or not GH plus nutritional therapy would be effective in promoting sustained catch-up growth remains to be determined.     

Prophylactic abciximab in elective coronary stenting: results of a randomized trial

BACKGROUND: The use of abciximab (c7E3 Fab; ReoPro , Eli Lilly & Company, Indianapolis, Indiana) during percutaneous coronary intervention (PCI) decreases the incidence of early (30-day) and late (6-month to 1 year) adverse cardiac ischemic events. In a high-risk population, abciximab also reduced the need for target lesion revascularization. PCI of lesions with complex morphology, particularly long lesions, is associated with more complicated outcomes. The use of multiple and/or long intracoronary stents to cover long coronary lesions may lower the incidence of acute or subacute occlusion, but is still limited by a high late restenosis rate. We characterized patients undergoing elective implantation of long or multiple overlapping coronary stents and determined the impact of abciximab administration on clinical and angiographic outcomes. METHODS AND RESULTS: In a prospective, single-center randomized trial, a total of 107 patients undergoing elective implantation of long or multiple overlapping coronary stents were randomly assigned to receive either standard-dose heparin (n = 53) or abciximab plus low-dose heparin (n = 54). The use of abciximab was not associated with an increased incidence of bleeding or vascular complications compared to standard heparin regimen (3.7% versus 3.8%, respectively; p = NS). A 68% reduction in composite in-hospital cardiac events (i.e., death, myocardial infarction, urgent revascularization) was observed in the abciximab group (3.7% versus 11.5%, p = 0.1). At 6-month follow-up, a 48% reduction of target lesion revascularization (11% versus 21%; p = 0.1) and a decrease in binary angiographic restenosis were observed for abciximab-treated patients (17% versus 34%; p < 0.05). CONCLUSION: The peri-procedural use of abciximab during implantation of long or multiple overlapping coronary stents is safe and effective, as it does not increase bleeding or vascular complications compared to standard heparin anticoagulation and reduces the incidence of in-hospital adverse cardiac events; moreover, abciximab improves 6-month clinical and angiographic outcomes in such a complex setting.     

Effect of rosiglitazone on restenosis after coronary stenting in patients with type 2 diabetes

Background

Thiazolidinediones have been shown to have an antiproliferative vascular effect in experimental models. We sought to study the effect of rosiglitazone on in-stent restenosis in patients with established type 2 diabetes.

Methods

Patients with treated type 2 diabetes (mean duration 5.5 ± 7.5 years) referred for coronary stenting were randomized in a double-blind fashion to receive oral rosiglitazone or placebo for 6 months. Quantitative coronary angiography and intravascular ultrasound data were obtained at baseline and follow-up. Plasma plasminogen activator inhibitor-1 levels were prospectively measured.

Results

Sixteen patients were enrolled. There were no significant differences in follow-up in-stent luminal diameter stenosis measured by quantitative coronary angiography or in-stent luminal area stenosis and neointimal volume index obtained by intravascular ultrasound, nor were there any differences in plasma plasminogen activator inhibitor-1 levels after long-term use despite improvement in diabetes control and insulin sensitivity.

Conclusions

Rosiglitazone, given at the time of stent implantation in treated diabetics, did not reduce in-stent restenosis in this small series. The vascular biological effects of this agent await further clarification in humans and evaluation in larger clinical trials.