Effect of probucol on neointimal thickening in a stent porcine restenosis model

Restenosis after stent deployment remains a major clinical problem. Antioxidants have been proposed as a promising strategy against restenosis. We tested the antioxidant probucol for its efficacy against neointimal hyperplasia in porcine coronary arteries after stent implantation. Probucol was then tested in vivo in 8 coronary arteries of 4 pigs (1000 mg/day orally beginning 7 days before stenting) and was compared to placebo (10 coronary arteries, 5 pigs) 28 days after stenting. Quantitative intravascular ultrasound (IVUS) revealed 38.8 +/- 4.0 versus 40.1 +/- 3.0% area stenosis in the probucol versus control group. Histopathologic assessment showed that probucol had no beneficial effect on inhibiting the neointimal proliferative response in stent lesions compared to placebo (2.35 +/- 0.26 versus 2.88 +/- 0.25 mm(2)), despite similar injury scores (1.20 +/- 0.12 versus 1.28 +/- 0.14). An edge segment (axially 2-mm proximal to the stent margins) was assessed by IVUS. Remodeling index, which is a good marker of constrictive remodeling, was defined by the ratio of the vessel area in the lesion site (stent edge) to the vessel area in the proximal reference site (6-mm proximal to the stent margins). The remodeling index was significantly larger in the probucol group that in the placebo group (1.18 +/- 0.10 versus 0.90 +/- 0.06, P = 0.0012). In conclusion, probucol reduced constrictive remodeling at the edge of the implant but did not inhibit the tissue response within the stent.     

Effect of anti-oxidant (carvedilol and probucol) loaded stents in a porcine coronary restenosis model.

BACKGROUND: The long-term clinical efficacy of intracoronary stenting is limited by restenosis and delivery by the stent of agents inhibiting cell cycle progression should prevent in-stent neointimal hyperplasia. Carvedilol is an antioxidant that inhibits smooth muscle cell proliferation and migration, whereas probucol is a vascular protectant and reduces stent restenosis by improving the lumen dimension at the stent placement site. METHODS AND RESULTS: BiodivYsio phosphorylcholine-coated stents were dip-coated with carvedilol (5 mg/ml) or probucol (50 mg/ml) by immersion in respective methanol solutions. Twenty-four stents (carvedilol=8, probucol=8, control=8) were placed in 12 pigs and histopathologic analysis was done 4 weeks later. Histomorphometry of the carvedilol-coated stent group compared with the control groups showed that the neointimal area decreased by 42% (1.12+/-0.55 mm2 in the carvedilol group vs 1.92+/-0.52 mm2 in the control, p=0.004) and the lumen area increased by 20% (5.15+/-0.90 mm2 vs 4.17+/-0.87 mm2, p=0.008), resulting in a 43% reduction of the percent area stenosis (18.22+/-9.6% vs 31.9+/-9.2%, p=0.002). In the probucol-coated stent group, the lumen area, neointimal area, and %area stenosis did not different significantly from the control group. There were 7.7+/-2.97% proliferating nuclear cell antigen-positive cells in the carvedilol-coated stent group compared with 17.8+/-1.45% in the control group (p=0.0001) and 15.9+/-1.91% in the probucol group (vs control, p=NS). CONCLUSIONS: The carvedilol-coated stent, but not the probucol-coated one, inhibited neointimal hyperplasia in a porcine stent restenosis model.     

Reduction in the rates of restenosis after coronary angioplasty with simvastatin and probucol

INTRODUCTION AND OBJECTIVES: The restenosis rates after coronary angioplasty persist as an important problem even though multiple drug therapies and different devices have been tried. The reduction of the cholesterol and low density lipoproteins levels (and their oxidation) have proved to have a beneficial effect on atherosclerosis evolution. Both the lipid lowering and antioxidant agents have caused a reduction in the neointimal formation generated with the angioplasty balloon in animals, and their combination to improve endothelial dysfunction in humans. The aim of the present study is to prove whether the whole administration of two potent agents such as simvastatin and probucol, which reduce the lipid levels and their oxidation, are able to lessen the restenosis related process. PATIENTS AND METHODS: Thirty five consecutive patients with coronary angioplasty with no stent to whom 20 mg simvastatin and 500 mg probucol bid were given (group-A) were studied in a prospective non-randomized study. They were compared to a historic group of 40 patients under the standard treatment (group-B). Both groups were angiographically evaluated to determine the restenosis percentage. A lipid profile was performed on group-A patients. RESULTS: The restenosis occurred in 4 (11.4%) in group-A and in 17 (42.5%) in group-B patients and in 4 (10.0%) and 18 (39.1%) lesions respectively (p < 0.01). A new PTCA was performed on 2 (5.7%) group-A patients vs 13 (32.5%) in group-B (p < 0.01). There was a reduction in residual stenosis (34.2 +/- 19.7% vs 48.8 +/- 23.5%, p < 0.01) and a greater minimum luminal diameter (1.76 +/- 0.59 vs 1.46 +/- 0.70 mm, p < 0.05) in group-A than in group-B patients. CONCLUSIONS: Although studies with more patients are required, a combined lipid lowering and antioxidant therapy could achieve a reduction in angioplasty coronary restenosis.     

普罗布考对合并糖尿病患者冠状动脉药物洗脱支架置入术后再狭窄及炎症因子的影响

目的评价普罗布考对合并糖尿病的冠心病患者药物洗脱支架置入术后再狭窄发生率及炎症因子的影响,初步探讨普罗布考预防再狭窄的临床价值及可能机制。方法入选72例合并糖尿病并接受药物洗脱支架置入术的冠心病患者,随机分为普罗布考组（36例）和对照组（36例）。普罗布考组在常规药物的基础上加服普罗布考（0.25 g,每日2次）,连续服药至PCI术后6个月,所有患者行冠状动脉造影复查。支架内再狭窄定义为支架内或两端5 mm内出现≥50%狭窄程度的病变。测定术前及术后6个月的血清超敏C反应蛋白、白细胞介素-6、肿瘤坏死因子-α的浓度变化。结果对照组中10例（27.8%）发生再狭窄,普罗布考组仅3例（8.3%）发生再狭窄,两组间比较,差异有统计学意义（P=0.032）;术后6个月时两组患者炎症因子水平较术前均有下降,普罗布考组下降更显著,差异具有统计学意义（P〈0.05）。结论普罗布考能够有效降低合并糖尿病的冠心病患者置入药物洗脱支架置入后再狭窄的发生,其机制可能与抗炎作用有关。     

普罗布考预防老年冠心病患者经皮冠状动脉介入治疗后再狭窄的临床观察

目的　观察抗氧化剂普罗布考预防老年冠心病患者经皮冠状动脉介入治疗 (PCI)后再狭窄的临床效果。方法　 6 2例患者随机分为普罗布考组 (32例 )和对照组 (30例 )。观察PCI前、后及随访 6个月冠状动脉造影、血清氧化指标氧化型低密度脂蛋白、丙二醛和内皮指标一氧化氮、内皮素变化情况。结果　随访 6个月时普罗布考组最小管腔直径和管腔净获得较对照组明显增加 [(2 .2± 0 .7)mmvs (l.4± 0 .3)mm ,P <0 .0 5 ;(1.8± 0 .4 )mmvs(0 .9± 0 .2 )mm ,P <0 .0 1) ],再狭窄率明显下降 (2 0 .2 %vs4 0 .0 % ,P <0 .0 5 ) ;血清氧化型低密度脂蛋白和丙二醛较对照组明显减少 [(0 .381± 0 .0 8)mg Lvs(0 .70 5± 0 .16 )mg L ,P <0 .0 1;(6 .2 0± 0 .5 7)nmol Lvs(l8.6 2± 2 .13)nmol L ,P <0 .0 1) ]。结论　抗氧化剂普罗布考可以降低PCI后 6个月冠状动脉再狭窄的发生率。     

Effects of candesartan and probucol on restenosis after coronary stenting: results of insight of stent intimal hyperplasia inhibition by new angiotensin II receptor antagonist (ISHIN) trial.

The purpose of this study was to determine whether candesartan and its combination with probucol reduce restenosis after coronary stenting. A total of 132 patients who successfully underwent stenting were randomly assigned to a control group (n=45), a candesartan group (8 mg daily, n=43), or a candesartan plus probucol group (+ probucol 500 mg daily, n=44). No differences in late loss were observed between the control and candesartan groups. In the candesartan plus probucol group, late loss was significantly smaller than in the control and candesartan groups (p=0.003, 0.015). The restenosis rate was 27% in the control group, 26% in the candesartan group (p>0.99), and 11% in the candesartan plus probucol group (p=0.104 vs the control group and p=0.103 vs the candesartan group). Intravascular ultrasound revealed no differences in stent area among the 3 groups, and no differences in lumen area or in intimal hyperplasia area between the control and candesartan groups. However, the intimal hyperplasia area in the candesartan plus probucol group was significantly less than that in the control and candesartan groups (p<0.001, p<0.001). This study demonstrated that candesartan failed to inhibit the neointimal hyperplasia and although the combination treatment did reduce neointimal hyperplasia, it did not statistically reduce the restenosis rate.     

辛伐他丁对支架新生内膜的作用

目的观察他丁类调脂药物对支架再狭窄和支架内新生内膜的影响.方法对单支冠脉病变行支架植入术的患者随机接受或不接受调脂药物的治疗,10月后复查冠脉造影和血管内超声检查.结果 65位患者随机接受辛伐他丁10mg治疗.辛伐他丁组患者在接受降脂治疗后血清总胆固醇降低15%,低密度脂蛋白胆固醇下降了26%,高密度脂蛋白胆固醇增加12%.辛伐他丁组和对照组支架再狭窄率无差异(分别为30.3%和37.5%,P>0.05).定量冠脉造影结果两组比较,两组参考段血管直径、支架最小管腔直径以及直径狭窄率均无明显差异.血管内超声发现辛伐他丁组参考段血管内膜腔截面积、最小血管内膜腔截面积以及最小支架截面积均无显著性差异.新生内膜截面积两组比较对照组大于辛伐他丁组,但无统计学意义.结论辛伐他丁长期治疗能够有效降低血中致动脉粥样硬化的脂蛋白.但10 mg/日的辛伐他丁对支架的再狭窄率以及支架内膜增生无明显影响.     

Impact of residual plaque burden after balloon angioplasty in the MultiVitamins and Probucol (MVP) trial

BACKGROUND: It has been shown in the MultiVitamins and Probucol (MVP) trial that probucol reduces angiographic lumen loss by 68% after percutaneous transluminal coronary angioplasty (PTCA). Restenosis occurred in 40% of patients not treated with probucol and in 20% of those in the probucol alone group. OBJECTIVE: To determine the morphological predictors of restenosis in patients treated with probucol. PATIENTS AND METHODS: Beginning 30 days before angioplasty, 317 patients were randomly assigned to receive probucol, multivitamins, the combined treatment or placebo. Patients were then treated for six months after angioplasty. Intravascular ultrasound (IVUS) examination was performed immediately after angioplasty and at follow-up in 94 patients (108 segments). The angioplasty operator was blinded to the IVUS results. The cross-section selected for serial analysis was the one at the angioplasty site with the smallest lumen area at follow-up. Receiver operating characteristic curves were used to determine the performance of criteria to predict angiographic restenosis at follow-up. RESULTS: In probucol-treated patients, the cross-sectional area (CSA) narrowing of 67.6% or less was the best IVUS predictor for the absence of restenosis (P=0.03). Diameter stenosis of 35% or less almost reached significance as a predictor in these patients (P=0.056). The restenosis rate when either of these predictors was met was less than 13%. Rates of repeat PTCA in patients treated with probucol were 9.7% when CSA narrowing was 67.6% or less on IVUS and 3.1% with a post-PTCA stenosis of 35% or less on quantitative coronary angiography (QCA). No predictor of the absence of restenosis in patients not treated with probucol was identified. CONCLUSIONS: The presence after balloon angioplasty of a CSA narrowing of 67.6% or less on IVUS or a diameter stenosis of 35% or less on QCA is associated, in patients treated with probucol, with extremely low rates of coronary restenosis and repeat angioplasty.     

普罗布考对糖尿病合并冠心病金属裸支架置入术后再狭窄预防的临床观察

目的观察抗氧化剂之乐（普罗布考）预防糖尿病合并冠心病金属裸支架置入术后后再狭窄的临床效果。方法163例糖尿病合并冠心病患者随机分为普罗布考组（87例）和对照组（76例）。观察PCI前、后及随访6个月冠状动脉造影、血清氧化型低密度脂蛋白情况。结果随访6个月时普罗布考组最小管腔直径和管腔净获得较对照组明显增加[（2．6±0．8）mm和（1．5±0．4）mm，P〈0．05；（1．7±0.3）mm和（0.8±0．1）mm，P〈0．01）]，再狭窄率明显下降（15．4％和38．8％，P〈0．05）。血清氧化型低密度脂蛋白较对照组明显减少[（0．372±0．06）mg／L和（0．597±40．14）mg／L，P〈0．01]；结论抗氧化剂普罗布考可以降低糖尿病合并冠心病金属裸支架置入术后6个月冠状动脉再狭窄的发生率。     

Influence of lesion length on restenosis after coronary stent placement

The length of a coronary lesion is a significant predictor of restenosis after balloon angioplasty. The influence of lesion length has not comprehensively been assessed after coronary stent placement. This study includes 2,736 consecutive patients with coronary stent placement. Only patients with recent or chronic occlusions before the intervention were excluded. Patients were divided in 2 groups: 573 patients with long lesions (≥15 mm) and 2,163 patients with short lesions (<15 mm). There were no significant differences between the groups with respect to the procedural success rate and incidence of subacute thrombosis. One-year event-free survival was lower in patients with long lesions (73.3% vs 80.0%, p = 0.001). Six-month angiography was performed in 82.5% of the eligible patients. The incidence of binary restenosis (≥50% diameter stenosis) was higher in patients with long lesions (36.9% vs 27.9%, p <0.001). Similarly, patients with long lesions presented more late lumen loss than those with short lesions (1.29 ± 0.89 vs 1.07 ± 0.77 mm, p <0.001). Multivariate models for both binary restenosis and late lumen loss demonstrated that lesion length was an independent risk factor for restenosis. The risk was further increased by multiple stent placement and overlapping stents that were also independent risk factors of restenosis. Stented segment length did not show any independent effect. Therefore, long lesions represent an independent risk factor for restenosis after coronary stent placement. The results of this study suggest that a possible way to reduce the risk is to cover the lesion with a minimal number of nonoverlapping stents.     

Probucol inhibits in-stent thrombosis and neointimal hyperplasia by promoting re-endothelialization

BACKGROUND: Evidence suggests that delayed re-endothelialization is responsible for in-stent thrombosis. Probucol inhibits neointimal thickening in animals via enhanced re-endothelialization and is the only oral drug that consistently inhibits restenosis after coronary angioplasty in humans. Here, we examined the effects of probucol on re-endothelialization and neointimal formation in a stent model. METHODS AND RESULTS: New Zealand White rabbits were fed a hypercholesterolemic diet with probucol (1%) or without (control) (n=11 each) for 6 weeks. At 2 weeks, endothelial denudation and stenting of the iliac artery was performed. Iliac arteries were harvested at week 6, and stented segments sectioned and analyzed. Compared with control, probucol increased in-stent re-endothelialization (74+/-6% in controls versus 93+/-3% in probucol-treated; P=0.008), and decreased average luminal stenosis (58+/-27 versus 31+/-16%; P=0.01) and stent depth (619+/-310 versus 314+/-158 microm; P=0.009). Compared with control, probucol also decreased accumulation of macrophages in the neointima. Furthermore, none of the probucol-treated rabbits had in-stent thrombosis, whereas four of eleven control rabbits showed thrombosis (P=0.04). CONCLUSIONS: Probucol demonstrates anti-restenotic and appears to have anti-thrombotic properties that are likely related to its ability to promote in-stent re-endothelialization.     

The relationship between preprocedural platelet size and subsequent in-stent restenosis

OBJECTIVE: Elevated mean platelet volume predicts restenosis after percutaneous transluminal coronary angioplasty but its effect on the development of in-stent restenosis is not known. We assessed the effect of mean platelet volume measured before coronary stent implantation for stable angina pectoris on subsequent development of in-stent restenosis. METHODS AND RESULTS: We retrospectively analysed the data of 60 patients who had stent implantation on one native coronary artery for stable angina pectoris and control angiographies for clinically suspected restenosis within 6 months. Mean platelet volume was measured by auto analyzer one day before stent implantation. Clinical and demographic data and laboratory results were obtained from the hospital charts of the patients. In-stent restenosis was evaluated visually from control angiograms. Angiographic in-stent restenosis was present in 35 (58%) of 60 patients and 25 (42%) patients had no restenosis. Mean platelet volume in the in-stent restenosis group was 8.28 +/- 0.71 fl compared to 7.63 +/- 0.74 fl in the no-restenosis group (p = 0.001). There was a positive correlation between preprocedural mean platelet volume and development of in-stent restenosis (r = 0.44; p < 0.001). A mean platelet volume value of > or = 8.4 fl was associated with an odds ratio of 16.0 for development of in-stent restenosis, with high specificity and positive predictivity but poor sensitivity and negative predictivity (96%, 93%, 40% and 53%, respectively). CONCLUSIONS: Mean platelet volume measured before stent implantation is correlated with subsequent development of in-stent restenosis. If preprocedural mean platelet volume is greater than 8.4 fl, in-stent restenosis is more probable to occur.     

Use of R ™ stent in the percutaneous coronary intervention of coronary bifurcation lesions

BACKGROUND: Percutaneous Coronary Intervention (PCI) of coronary bifurcation lesion is technically quite demanding. It has been associated with a lower procedural success, higher rates of complication and restenosis. Side-branch occlusion and plaque shifting or 'snow plow' effect are not uncommon. Stenting of the main vessel may cause 'stent jail' of the side-branch. Modern stent design may allow passage of a balloon or stent into the side-branch through the struts of the stent placed in the main vessel. A newly developed 316 stainless steel tubular stent, the R? stent is uniquely designed to provide flexibility, radial strength on deployment and conformability. Its large cell size facilitates PCI of bifurcation lesion. AIM: To assess the feasibility of R ? stent in the treatment of symptomatic patients with bifurcation coronary lesions. The main objective was to assess the ease of deployment, side-branch access and overall success of the R ? stent in this group of patients without any major adverse events. METHODS: Between December 1998 and September 2000 the R ? stent was used as a main stent in 28 consecutive patients with coronary bifurcation lesions, 46% of which had unstable angina. The mean age was 59 &#45 10 and 89% were male. Adjunctive medical therapy included clopidrogel, aspirin and intraprocedure heparin. Abciximab (ReoPro) was given to 9 patients. RESULTS: Successful stent deployment was achieved in all patients. Thirty-four R Stents and 16 other stents were used. Two patients had post-procedure rise in cardiac enzymes. There were no major adverse events at 30 days. LAD/D1 with LAD/diagonal was the target lesion in the majority of patients. Stenting of the side-branch was done in 18 and balloon dilatation in 9 patients. At 3-23 months (mean 11.8) follow-up, repeat angiography was done in 18 patients with restenosis in 4, two of them had repeat PCI and one had coronary artery bypass graft (CABG). CONCLUSION: Coronary bifurcation lesions are not uncommon. Current advances in stent technology offer a safe and effective revascularisation strategy for such complex lesions. The R ? stent appears to be a suitable device that provides good wall coverage, radial strength, conformability and easy side-branch access.     

Effects of statins on restenosis after coronary stent implantation

Experimental data and preliminary clinical studies suggest that lipid-lowering drugs might have a beneficial effect on restenosis after coronary angioplasty. Recently, statins have been focused on prevention of restenosis after coronary stent implantation. However, their benefit has not yet been established. The authors studied the effects of statins on stent restenosis. We compared retrospectively the quantitative coronary angiographic (QCA) variables between 62 dyslipidemic patients treated with statins (pravastatin or fluvastatin) and 62 normolipidemic patients, as a control, treated without statins after undergoing successful coronary stent implantation with 6-month follow-up angiography from May 1999 to December 2002. Major cardiac events were about the same in both groups. Each of the QCA variables before and immediately after coronary stenting was similar in the 2 groups. At follow-up angiography, however, minimal lumen diameter (MLD) (2.12 -/+ 0.73 vs 1.78 -/+ 0.7; p < 0.01) was larger in the statin group than in the normolipidemia group. Both restenosis rate (15% vs 31%; p = 0.05) and target lesion revascularization rate (10% vs 24%; p = 0.05) were lower in the statin group than in the normolipidemia group. Statin reduced restenosis rate. The efficacy of statins appears to be dependent on their pleiotropic effects on vascular wall rather than on lipid-lowering effects.     

Diabetes mellitus and the clinical and angiographic outcome after coronary stent placement

Objectives. The objectives of this study were to analyze the clinical and angiographic outcome of diabetic patients with successful coronary stent placement and to compare these results with those achieved after stenting in nondiabetic patients.

Background. The outcome of diabetic patients treated with stent placement due to coronary artery disease has not been assessed comprehensively.

Methods. This study analyzes a consecutive series of patients with successful stent placement comprising 715 patients with diabetes and 2,839 patients without diabetes. Clinical one year follow-up and angiographic control at 6 months were part of the protocol. Death, myocardial infarction and target lesion revascularization were considered as adverse events. An automated edge detection system was used for the angiographic assessment. The primary clinical endpoint was event-free survival at one year. The primary angiographic endpoint was restenosis rate at 6 months (≥50% diameter stenosis).

Results. Event-free survival was significantly lower in diabetic than in nondiabetic patients (73.1 vs. 78.5%, p < 0.001). Survival free of myocardial infarction was also significantly reduced in the diabetic group (89.9 vs. 94.4% in nondiabetics, p < 0.001). The incidence of both restenosis (37.5 vs. 28.3%, p < 0.001) and stent vessel occlusion (5.3 vs. 3.4%, p = 0.037) was significantly higher in diabetic patients. Diabetes was identified as an independent risk factor for adverse clinical events and restenosis in multivariate analyses.

Conclusions. Patients with diabetes mellitus have a less favorable clinical outcome at one year after successful stent placement as compared to the nondiabetic patients. The clinical follow-up was characterized by a higher incidence of death, myocardial infarction and reinterventions. Diabetic patients also demonstrated an increased risk for restenosis.     

Clinical significance of fractional flow reserve for evaluation of functional lesion severity in stent restenosis and native coronary arteries

OBJECTIVE: Fractional flow reserve (FFR) is a valid surrogate for hemodynamic significance in stenotic native coronary arteries, but its validity in patients with coronary stent restenosis is unknown. DESIGN: Prospective. SETTING: University hospital. PATIENTS: We studied 42 patients (mean age +/- 1 SD, 62 +/- 10 years) with stent restenosis and 57 patients (mean age, 61 +/- 12 years) with a native coronary lesion. All patients demonstrated a single coronary lesion of intermediate severity (stenosis diameter, 40 to 70%). Determination of FFR and quantitative angiography of the stenosis were performed. RESULTS: Stenosis diameter was comparable in both groups (native, 52 +/- 11%; stent, 52 +/- 9%; not significant [NS]). FFR was lower in stent restenosis (0.77 +/- 0.15 vs 0.82 +/- 0.12, p < 0.05) and more often pathologic with an FFR < 0.75 (48% vs 26%, p < 0.05) compared to native coronary stenosis. However, the area under the receiver operating characteristic curve for native stenosis was 0.82 (95% confidence interval [CI], 0.71 to 0.94) and for stent restenosis was 0.84 (95% CI, 0.71 to 0.97; NS). In patients with an FFR > 0.75, there was no adverse coronary event that was related to the stented lesion in the subsequent 6 months. CONCLUSIONS: The threshold of stenosis diameter of coronary lesions for pathologic FFR measurement (FFR < 0.75) is similar for stent restenosis and native coronary stenosis. Thus, FFR measurement seems to be applicable for decision making in patients with stent restenosis.     

Relation between residual plaque burden after stenting and six-month angiographic restenosis

The degree of residual plaque burden outside of a stent might be correlated with the degree of intimal hyperplasia. However, the relation between residual plaque burden and angiographic restenosis are still unknown in a large number of patients. Therefore, we evaluated the effect of residual plaque burden after stenting on 6-month angiographic restenosis. Intravascular ultrasound (IVUS)-guided coronary stenting was successfully performed in 723 patients with 785 native coronary lesions. Six-month follow-up angiograms and evaluation of residual plaque burden by IVUS were available in 566 patients (78.3%) with 622 lesions (79.2%). Results were evaluated using conventional methods. The overall angiographic restenosis rate was 23.0% (143 of 622 lesions). There was no significant difference in residual plaque burden between the lesions with and without restenosis (52% vs 51%, respectively, p = 0.148). The angiographic restenosis rate was 20.8% (11 of 53 lesions), 21.6% (51 of 236 lesions), 22.0% (55 of 250 lesions), and 31.3% (26 of 83 lesions) in the lesions with residual plaque burden < 40%, between 40% and 50%, between 50% and 60%, and > 60%, respectively (p = 0.284). Using multivariate logistic regression analysis, the only independent predictor of angiographic restenosis was the IVUS stent area (odds ratio 0.807, 95% confidence intervals 0.69 to 0.95, p = 0.011). Furthermore, even in the lesions with residual plaque burden > 60%, the restenosis rate was 37.3% (23 of 61 lesions) versus 13.6% (3 of 22 lesions ) in IVUS stent areas of < 7 and > or =7 mm(2), respectively (p = 0.031). In conclusion, residual plaque burden outside the stent might not predict angiographic restenosis. IVUS stent area was the only independent predictor of angiographic restenosis.     

Preventive effects of the heparin-coated stent on restenosis in the porcine model.

The coronary stent reduces acute coronary arterial occlusion and late restenosis during and after coronary intervention. However, stent thrombosis and restenosis are still major limitations in the widespread use of the coronary stent. Local drug delivery using the heparin-coated stent may be a new approach, which reduces the incidence of stent thrombosis and restenosis. In order to evaluate the effects of the heparin-coated stent on stent restenosis, heparin-coated stents were compared with control stents in a porcine coronary stent restenosis model. Stent overdilation injury (stent:artery = 1.3:1.0) was performed with bare Wiktor stents (group I, n = 10) and heparin-coated Wiktor stents (group II, n = 20; HEPAMED, Medtronics) in porcine coronary arteries. Follow-up quantitative coronary angiography (QCA) was performed at 4 weeks after stenting, and histo-pathologic assessments of stented porcine coronary arteries were compared in both groups. On QCA, percent diameter stenosis was significantly higher in group I than in group II (16.3% +/- 6.62% vs. 9.6% +/- 5.06%, P < 0.05). The injury score of stented porcine coronary arteries was the same in both groups (1. 26 +/- 0.23 vs. 1.20 +/- 0.22). The area of pathologic stenosis of the stented arteries was higher in group I than in group II (41.6% +/- 12.5% vs. 27.1% +/- 9.9%, P < 0.005). The neointimal area was higher in group I than in group II (4.58 +/- 1.41 mm(2) vs. 2.57 +/- 1.07 mm(2), P < 0.05). By immunohistochemistry, the proliferating cell nuclear antigen (PCNA) index was higher in group I compared with group II (11.2% +/- 6.75% vs. 6.3% +/- 4.14%, P < 0.05). The heparin-coated stent is effective in the prevention of late coronary stent restenosis in a porcine coronary stent restenosis model. This may be related to the inhibition of neointimal cell proliferation.     

Effects of probucol versus aspirin and versus brachytherapy on restenosis after femoropopliteal angioplasty: the PAB randomized multicenter trial.

PURPOSE: To evaluate the effect of probucol and/or of endovascular brachytherapy (EVBT) on restenosis after percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries. METHODS: A total of 335 patients (206 men; mean age 72+/-9 years) with intermittent claudication were randomized according to a 2x2 factorial design to 1 of the 4 groups: probucol, placebo, EVBT, and EVBT+probucol. Probucol (1 g/d) or placebo were given in double-blinded fashion 1 month before and for 6 months after PTA. Gamma irradiation (192Iridium, 14 Gy, 5-mm reference depth) was randomly applied in an unblinded manner from a noncentered endoluminal catheter. All patients received aspirin (100 mg/d). Primary endpoint was restenosis (>50% diameter reduction) detected by duplex ultrasound 6 months after PTA. Secondary endpoints included clinical and hemodynamic assessment. RESULTS: Restenosis in patients undergoing EVBT was 17% (23/133) versus 35% (50/142) in patients without EVBT (p<0.001); in patients treated with probucol versus placebo, the rates were 23% (31/135) and 30% (43/140, p<0.001). Three quarters (77%, 102/133) of patients were free of claudication after EVBT therapy versus 61% (87/142) without EVBT (p<0.05). Need for target vessel revascularization was 6% (8/133) with EVBT versus 14% (20/142) without EVBT (p<0.01). Late thrombotic occlusions occurred in 4% (6/133), exclusively in patients treated with EVBT after stent implantation. CONCLUSIONS: Endovascular brachytherapy significantly reduces restenosis, improves symptoms, and reduces reinterventions after PTA of femoropopliteal arteries. Probucol reduces restenosis but has no additive effect when combined with brachytherapy.     

Balloon angioplasty for the treatment of coronary in-stent restenosis: immediate results and 6-month angiographic recurrent restenosis rate

Objectives. The purpose of this prospective study was to evaluate the immediate results and the 6-month angiographic recurrent restenosis rate after balloon angioplasty for in-stent restenosis.Background. Despite excellent immediate and mid-term results, 20% to 30% of patients with coronary stent implantation will present an angiographic restenosis and may require additional treatment. The optimal treatment for in-stent restenosis is still unclear.Methods. Quantitative coronary angiography (QCA) analyses were performed before and after stent implantation, before and after balloon angioplasty for in-stent restenosis and on a 6-month systematic coronary angiogram to assess the recurrent angiographic restenosis rate.Results. Balloon angioplasty was performed in 52 patients presenting in-stent restenosis. In-stent restenosis was either diffuse (≥ 10 mm) inside the stent (71%) or focal (29%). Mean stent length was 16 ± 7 mm. Balloon diameter of 2.98 ± 0.37 mm and maximal inflation pressure of 10 ± 3 atm were used for balloon angioplasty. Angiographic success rate was 100% without any complication. Acute gain was lower after balloon angioplasty for in-stent restenosis than after stent implantation: 1.19 ± 0.60 mm vs. 1.75 ± 0.68 mm (p = 0.0002). At 6-month follow-up, 60% of patients were asymptomatic and no patient died. Eighteen patients (35%) had repeat target vessel revascularization. Angiographic restenosis rate was 54%. Recurrent restenosis rate was higher when in-stent restenosis was diffuse: 63% vs. 31% when focal, p = 0.046.Conclusions. Although balloon angioplasty for in-stent restenosis can be safely and successfully performed, it leads to less immediate stenosis improvement than at time of stent implantation and carries a high recurrent angiographic restenosis rate at 6 months, in particular in diffuse in-stent restenosis lesions.