BACKGROUND & AIMS: BACKGROUND:Uncertainties still remain in terms of what kinds of patients benefit most from cilostazol-based triple antiplatelet therapy (TAT) after coronary stenting. METHODS:We performed a meta-analysis of all relevant randomized controlled trials (RCTs) to investigate the effect of TAT versus dual antiplatelet therapy (DAT) in terms of major adverse cardiovascular events (MACEs) in patients undergoing coronary stenting. RESULTS:Fourteen RCTs with 5,821 patients were included in this study. TAT was associated with a significant reduction in the risk of MACEs compared to DAT [9.2 vs. 13.4%; odds ratio 0.59 (0.46, 0.76)] with consistent benefits among patients with diabetes, long lesions and small vessels. There were no significant between-group differences in the risk of cardiac death, myocardial infarction, stent thrombosis and bleeding events; however, the risk of target lesion revascularization was significantly lower in the TAT group. TAT resulted in borderline significant reduction in the risk of cardiovascular thrombotic events in unselected patients and significant decrease in patients with acute coronary syndrome [odds ratio 0.51 (0.27, 0.94)]. CONCLUSION:Under the treatment of standard DAT, the addition of cilostazol is an effective and relatively safe strategy in preventing MACEs after coronary stenting, especially for patients at high risk of restenosis or clinical events.

背景与目标：

BACKGROUND & AIMS: Prior to this study, cilostazol, an antithrombotic drug, was thought to exist as a single crystalline phase with a melting point of approximately 159 degrees C (Form A). On cooling, melts often form a glass that, when heated, may crystallize as additional crystalline polymorphic forms. Cilostazol, when reheated, subsequently forms polymorphs that melt at approximately 136 degrees C (Form B) and 146 degrees C (Form C). Free-energy temperature diagrams estimated from calorimetry data reveal that each pair of the cilostazol polymorphs (A-B, B-C, and A-C) is monotropic. Essentially pure samples of suitable crystalline shape and size permitted single crystal structural analysis of Forms A and C. Theoretical solubility ratios calculated using calorimetry data indicate that at 37 degrees C, Form B should be more than four times more soluble and Form C should be more than two times more soluble than Form A. Forms B and C could not be crystallized from solvents. Metastable forms from super cooled melts analyzed by intrinsic dissolution and Fourier transform-Raman experiments demonstrated that Forms B and C undergo a rapid, solvent-mediated recrystallization to Form A, making dissolution rate measurements difficult.

背景与目标： 在该研究之前，认为抗血栓形成药物西洛他唑以具有约159 ℃ (形式a) 的熔点的单晶相存在。冷却时，熔体通常会形成玻璃，加热后可能会结晶为其他晶体多晶型形式。当再次加热时，西洛他唑随后形成在大约136 ℃ (形式B) 和146 ℃ (形式C) 熔化的多晶型物。根据量热法数据估算的自由能温度图表明，每对西洛他唑多晶型物 (A-B，B-C和A-C) 都是单向的。具有合适晶体形状和尺寸的基本纯样品允许对A和C型进行单晶结构分析。使用量热法数据计算的理论溶解度比表明，在37 ℃ 下，形式B的可溶性应该是形式A的四倍以上，形式C的可溶性应该是形式A的两倍以上。形式B和C不能从溶剂中结晶。通过固有溶解和傅里叶变换拉曼实验分析的过冷熔体的亚稳态形式表明，形式B和C经历了快速的，溶剂介导的重结晶形式形成a，从而使溶解速率测量变得困难。

BACKGROUND & AIMS: :Cilostazol is a potent type III phosphodiesterase inhibitor with pharmacological effects that include vasodilatation, inhibition of platelet activation and aggregation, inhibition of thrombosis, increased blood flow to the limbs, improvement in serum lipids with lowering of triglycerides and elevation of high density lipoprotein cholesterol, and inhibition of vascular smooth muscle cell growth. It operates through its action as endothelium-target antithrombotic therapy, achieving its effects by improving endothelial cell function and reducing the number of platelets partially activated by interacting with activated endothelial cells. Since receiving approval from the Food and Drug Administration in 1999 in the United States for the treatment on intermittent claudication secondary to peripheral arterial disease, new data on its role on the prevention of restenosis after percutaneous transluminal angioplasty and the secondary prevention of cerebral infarction have increased interest in the drug. The aim of this study is to review cilostazol's beneficial effects and adverse events, and to present the results of the major clinical trials.

背景与目标： : 西洛他唑是一种有效的III型磷酸二酯酶抑制剂，具有药理作用，包括血管舒张，抑制血小板活化和聚集，抑制血栓形成，增加四肢血流量，通过降低甘油三酸酯和升高来改善血脂高密度脂蛋白胆固醇，并抑制血管平滑肌细胞生长。它通过其作为内皮靶向抗血栓治疗的作用而发挥作用，通过改善内皮细胞功能并减少通过与活化的内皮细胞相互作用而部分激活的血小板数量来实现其作用。自从获得美国食品药品监督管理局 (Food and Drug Administration) 1999年批准治疗继发于外周动脉疾病的间歇性跛行以来，有关其在预防经皮腔内血管成形术后再狭窄和脑梗塞二级预防中的作用的新数据增加了人们对该药物的兴趣。本研究的目的是回顾西洛他唑的有益作用和不良事件，并介绍主要临床试验的结果。

BACKGROUND & AIMS: BACKGROUND AND PURPOSE:The present study assessed the effects of cilostazol on LPS-stimulated TLR4 signal pathways in synovial macrophages from patients with rheumatoid arthritis (RA). These effects were confirmed in collagen-induced arthritis (CIA) in mice. EXPERIMENTAL APPROACH:Expression of TLR4, PU.1, NF-κB p65 and IκBα on synovial fluid macrophages from RA patients was determined by Western blotting, and cytokines were measured by ELISA. Anti-arthritic effects were evaluated in CIA mice. KEY RESULTS:Intracellular cAMP was concentration-dependently raised by cilostazol (1-100 μM). Cilostazol significantly suppressed LPS-stimulated increase of TLR4 expression by blocking PU.1 transcriptional activity in RA macrophages. In addition, cilostazol decreased LPS-induced myeloid differentiation factor 88 (MyD88) expression, but not that of TNF receptor-associated factor 6 (TRAF6). Cilostazol also suppressed IkBα degradation and NF-κB p65 nuclear translocation. Moreover, LPS-induced increase of cytokine production (TNF-α, IL-1β) was inhibited by cilostazol, an effect which was accompanied by suppression of IκBα degradation, and NF-κB p65 nuclear translocation. However, expression of anti-inflammatory IL-10 was elevated by cilostazol and forskolin/IBMX. In mice with CIA, post-treatment with cilostazol (30 mg kg⁻¹ day⁻¹) decreased expression of TLR4 in knee joints in association with decreased recruitment of macrophages. Consequently, synovial inflammation, proteoglycan depletion and bone erosion were significantly inhibited by cilostazol treatment. CONCLUSIONS AND IMPLICATIONS:Cilostazol down-regulated LPS-stimulated PU.1-linked TLR4 expression and TLR4/MyD88/NF-κB signal pathways, and then suppressed inflammatory cytokine production in synovial macrophages from RA patients. Also cilostazol markedly inhibited the severity of CIA in mice.

背景与目标：

BACKGROUND & AIMS: :Peripheral arterial disease may lead to lower limb claudication and increased risk of systemic vascular dysfunction. In this article, the authors have investigated the peripheral vascular dysfunction evaluating forearm blood flow using venous occlusion plethysmography, lipid profile, and C-reactive protein in 60 patients with moderate intermittent claudication treated during 20 weeks with placebo (n = 16), cilostazol (200 mg/d; n = 17), or pentoxifylline (1200 mg/d; n = 15) in a randomized double-blinded clinical trial, taking into account smoking. Forearm blood flow after reactive hyperemia response (FBF(h) ) or oral nitroglycerine spray to evaluate endothelial-dependent and endothelial-independent vasodilation, respectively, pain-free and maximal walking distance, levels of C-reactive protein, triglycerides, cholesterol, low-density lipoprotein, and high-density lipoprotein-cholesterol in plasma were determined. The results showed that there was an improvement in the high-density lipoprotein-cholesterol, pain-free and maximal walking distance, and FBF(h) independent of treatment in nonsmoking patients. Cilostazol increased high-density lipoprotein-cholesterol level, maximal walking distance, and FBF(h), whereas pentoxifylline reduced C-reactive protein level and increased maximal walking distance in total and nonsmoking groups. No treatment was effective in smokers.

背景与目标： 周围动脉疾病可能导致下肢跛行和增加全身血管功能障碍的风险。在本文中，作者研究了使用安慰剂 (n = 16)，西洛他唑 (200 mg/d; n = 17) 治疗20周的60例中度间歇性跛行患者的静脉闭塞体积描记术，脂质分布和C反应蛋白评估前臂血流的周围血管功能障碍。在考虑吸烟的随机双盲临床试验中或己酮可可碱 (1200 mg/d; n = 15)。反应性充血反应 (FBF(h)) 或口服硝酸甘油喷雾剂后前臂血流分别评估内皮依赖性和内皮依赖性血管舒张，无痛和最大步行距离，C反应蛋白水平，甘油三酸酯，胆固醇，低密度脂蛋白，并测定血浆中的高密度脂蛋白胆固醇。结果表明，在非吸烟患者中，高密度脂蛋白胆固醇，无痛和最大步行距离以及FBF(h) 的改善与治疗无关。西洛他唑增加了高密度脂蛋白胆固醇水平，最大步行距离和FBF(h)，而己酮可可碱降低了总吸烟组和非吸烟组的C反应蛋白水平并增加了最大步行距离。没有治疗对吸烟者有效。

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVES:Peripheral artery disease (PAD) is common in patients on hemodialysis (HD). Recently, cilostazol has been reported to reduce target lesion revascularization (TLR) after percutaneous transluminal angioplasty (PTA) for PAD in the general population. This study aimed to clarify the effects of cilostazol administration on long-term patency after PTA in HD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Three-hundred seventy-two consecutive lesions in 193 HD patients successfully undergoing PTA were enrolled in the study and divided into two groups: patients receiving 100 mg cilostazol twice daily in conjunction with standard therapy (130 lesions in 71 patients) and those not administered cilostazol (242 lesions in 122 patients). Effects of cilostazol on preventing restenosis after PTA in these patients were investigated. RESULTS:Kaplan-Meier analysis demonstrated the 5-yr patency rate was significantly higher in the cilostazol group than in the control group [52.4 versus 32.9%, hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.39 to 0.77, P = 0.0005]. Cox multivariate analysis revealed that administration of cilostazol was an independent predictor of preventing restenosis (HR 0.56, 95% CI 0.36 to 0.87, P = 0.010). In 102 lesions matched after propensity score analysis, cilostazol had a beneficial effect on preventing restenosis (58.4 versus 34.7%, HR 0.47, 95% CI 0.30 to 0.75, P = 0.0017) and was an independent predictor of preventing restenosis (HR 0.50; 95% CI 0.26 to 0.87, P = 0.014) after multivariate Cox analysis. CONCLUSIONS:Cilostazol administration improves long-term patency after PTA in HD patients with PAD.

背景与目标：

BACKGROUND & AIMS: BACKGROUND/AIMS:Cilostazol has been previously demonstrated to inhibit IL-23 production in human synovial macrophages via a RhoA/ROCK-dependent pathway. However, whether cilostazol affects IL-23 production in human dendritic cells remains largely unknown. The present study was designed to investigate this question and elucidate the possible underlying mechanisms. METHODS:Human monocyte-derived dendritic cells (mo-DCs) were pretreated with or without cilostazol and then incubated with zymosan. Enzyme-linked immunosorbent assay (ELISA) and real time PCR analyses were used to measure IL-23 protein expression and RNA levels, respectively, whereas Western blotting was used to measure the expression and phosphorylation level of AMPK. RESULTS:Our results demonstrated that cilostazol suppressed zymosan-induced IL-23 protein production in a concentration dependent manner without affecting dendritic cell viability. In addition, it was found that cilostazol suppressed the expression of the p19 and p40 subunits of IL-23. Moreover, cilostazol mimicked the effect of the AMPK agonist A-769662, as demonstrated by the fact that IL-23 production was also inhibited by A-769662, and the effect of cilostazol on IL-23 production was blocked by the AMPK antagonist Compound C. More importantly, Western blotting demonstrated that cilostazol led to an increased phosphorylation of AMPK. CONCLUSION:Collectively, our data suggest that cilostazol inhibits the production of IL-23 in human mo-DCs, potentially via the activation of AMPK. This suggests that cilostazol could be an effective anti-inflammatory agent in IL-23- and dendritic cell-related diseases.

背景与目标：

BACKGROUND & AIMS: AIM:Angiotensin converting enzyme inhibitors and alpha1-adrenergic blockers improve insulin sensitivity, the mechanism of which was considered, at least in part, to be due to the increased blood flow to muscle. The present study aimed to clarify whether cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in a model of spontaneous non-insulin dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rat. METHODS:OLETF rats were divided into the two groups at the age of 16 weeks: the cilostazol-supplemented group (cilostazol 40 mg/kg/day) and the normal-diet group. As a non-diabetic control, we used Long-Evans-Tokushima-Otsuka rats (non-diabetic rats). Oral glucose tolerance test and hyperinsulinemic euglycemic clamp was performed at the ages of 23 and 25 weeks, respectively. Serum levels of lipids and leptin were measured. RESULTS:Body weight and abdominal fat was increased in OLETF rats but cilostazol supplementation did not alter them. Insulin sensitivity, as measured by the hyperinsulinemic euglycemic clamp technique, was significantly decreased in OLETF rats (glucose infusion rate: 73.5 +/- 10.0 vs. 41.5 +/- 9.8 micromol/min/kg body weight, p < 0.01). Cilostazol supplementation improved insulin sensitivity partially but significantly 51.0 +/- 5.7 micromol/min/kg body weight, p < 0.05) in OLETF rats at 25 weeks of age, although it did not decrease serum levels of glucose, lipids or leptin. However, this effect was not observed in non-diabetic rats. CONCLUSION:Cilostazol, which is used in diabetic patients for the treatment of obstructive disease of artery, is expected to have a beneficial effect on insulin sensitivity in NIDDM.

背景与目标：

BACKGROUND & AIMS: :Liver failure after extended hepatectomy represents a major challenge in the surgery of hepatic colorectal metastasis. A previous study has indicated that inhibition of phosphodiesterase type 3 (PDE 3) stimulates liver regeneration. However, little is known whether PDE 3 inhibitors, such as cilostazol, also stimulate the growth of remnant metastases. Therefore, we herein studied the effect of cilostazol on engraftment, vascularization and growth of colorectal liver metastasis after major hepatectomy. WAG-rats underwent either major hepatectomy or sham operation. Metastases were induced by subcapsular implantation of 5 × 10(5) CC531-colorectal cancer cells. Animals were daily treated with cilostazol (5 mg/kg body weight) or glucose solution. Tumor growth was measured by high-resolution ultrasound at days 7 and 14. Tumor vascularization and tumor cell proliferation were determined by immunohistochemistry and western blotting. High-resolution ultrasound analysis in hepatectomized and non-hepatectomized animals showed that cilostazol does not stimulate tumor growth. Accordingly, the number of PCNA-positive tumor cells did not differ between cilostazol-treated animals and sham-treated controls. Interestingly, cilostazol reduced tumor vascularization in both hepatectomized and non-hepatectomized animals. This was indicated by a significantly lower number of platelet-endothelial cell adhesion molecule (PECAM-1)-positive cells in tumors of cilostazol-treated animals compared to sham-treated controls. The PDE 3 inhibitor cilostazol does not stimulate the growth of colorectal metastases during liver regeneration after major hepatectomy.

背景与目标： : 扩大肝切除术后的肝衰竭是肝结直肠转移手术中的主要挑战。先前的研究表明，抑制3型磷酸二酯酶 (PDE 3) 可刺激肝再生。然而，尚不清楚PDE 3抑制剂 (例如西洛他唑) 是否也刺激残余转移的生长。因此，我们在此研究了西洛他唑对大肝切除术后结直肠肝转移的植入，血管形成和生长的影响。WAG-大鼠接受了主要的肝切除术或假手术。通过5 × 10(5) CC531-colorectal癌细胞的包膜下植入诱导转移。每天用西洛他唑 (5 mg/kg体重) 或葡萄糖溶液处理动物。在第7天和第14天通过高分辨率超声测量肿瘤生长。通过免疫组织化学和western印迹法确定肿瘤血管形成和肿瘤细胞增殖。肝切除和非肝切除动物的高分辨率超声分析表明，西洛他唑不会刺激肿瘤生长。因此，在西洛他唑处理的动物和假治疗的对照组之间，PCNA阳性肿瘤细胞的数量没有差异。有趣的是，西洛他唑减少了肝切除和非肝切除动物的肿瘤血管形成。与假治疗的对照组相比，在西洛他唑治疗的动物的肿瘤中血小板-内皮细胞粘附分子 (PECAM-1) 阳性细胞的数量明显减少，表明了这一点。PDE 3抑制剂西洛他唑不会刺激大肝切除术后肝再生过程中结直肠转移瘤的生长。

BACKGROUND & AIMS: Objective:Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Methods:Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Results:Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76-39.71%); group C, 16.21% (95% CI, 13.36-19.05%); and group A, 21.12% (95% CI, 17.26-25.01%); P < 0.0001. Conclusion:We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol.

背景与目标：

BACKGROUND & AIMS: :Mitochondrial dysfunction is frequently observed in vascular diseases. Cilostazol is a drug approved by the US Food and Drug Administration for the treatment of intermittent claudication. Cilostazol increases intracellular cyclic adenosine monophosphate (cAMP) levels through inhibition of type III phosphodiesterase. The effects of cilostazol in mitochondrial biogenesis in human umbilical vein endothelial cells (HUVECs) were investigated in this study. Cilostazol treated HUVECs displayed increased levels of ATP, mitochondrial DNA/nuclear DNA ratio, expressions of cytochrome B, and mitochondrial mass, suggesting an enhanced mitochondrial biogenesis induced by cilostazol. The promoted mitochondrial biogenesis could be abolished by Protein kinase A (PKA) specific inhibitor H-89, implying that PKA pathway played a critical role in increased mitochondrial biogenesis after cilostazol treatment. Indeed, expression levels of peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), NRF 1 and mitochondrial transcription factor A (TFAM) were significantly increased in HUVECs after incubation with cilostazol at both mRNA levels and protein levels. Importantly, knockdown of PGC-1α could abolish cilostazol-induced mitochondrial biogenesis. Enhanced expression of p-CREB and PGC-1α induced by cilostazol could be inhibited by H-89. Moreover, the increased expression of PGC-1α induced by cilostazol could be inhibited by downregulation of CREB using CREB siRNA at both mRNA and protein levels. All the results indicated that cilostazol promoted mitochondrial biogenesis through activating the expression of PGC-1α in HUVECs, which was mediated by PKA/CREB pathway.

背景与目标： 线粒体功能障碍在血管疾病中经常观察到。西洛他唑是美国食品药品监督管理局批准用于治疗间歇性跛行的药物。西洛他唑通过抑制III型磷酸二酯酶来增加细胞内环磷酸腺苷 (cAMP) 的水平。本研究研究了西洛他唑对人脐静脉内皮细胞 (HUVECs) 线粒体生物发生的影响。西洛他唑处理的huvec显示出ATP水平升高，线粒体DNA/核DNA比率，细胞色素B表达和线粒体质量，表明西洛他唑诱导的线粒体生物发生增强。蛋白激酶A (PKA) 特异性抑制剂H-89可以消除促进的线粒体生物发生，这表明PKA途径在西洛他唑治疗后增加线粒体生物发生中起关键作用。实际上，与西洛他唑在mRNA水平和蛋白质水平孵育后，过氧化物酶体增殖物激活剂受体 γ-共激活剂1α (PGC-1α)，NRF 1和线粒体转录因子A (TFAM) 的表达水平在HUVECs中显着增加。重要的是，敲除PGC-1α 可以消除西洛他唑诱导的线粒体生物发生。H-89可以抑制西洛他唑诱导的p-CREB和PGC-1α 的表达。此外，使用CREB siRNA在mRNA和蛋白质水平上下调CREB可以抑制西洛他唑诱导的PGC-1α 表达增加。所有结果表明，西洛他唑通过激活PKA/CREB途径介导的HUVECs中PGC-1α 的表达来促进线粒体生物发生。

BACKGROUND & AIMS: OBJECTIVE:Several reports have indicated that cilostazol is effective in the prevention of recurrence after cerebral infarction. However, cilostazol is inferior in tolerability for the adverse events than other anti-platelet agents. The goal of this study was to determine whether cilostazol escalation oral administration affects its tolerability. METHODS:One hundred sixty-eight patients hospitalized for brain infarction with cilostazol treatment in our stroke center from 2006 to 2008 were enrolled in this study. During this term, we had two teams in our center and used different regimens. One of which used 100 mg b.i.d. regimen of cilostazol (Standard group) and the other used 50 mg b.i.d. for the initial 4 days, followed by a dose of 100 mg b.i.d. of it (Escalation group). Patient's information such as baseline characteristics, adverse events, were collected and statistically analyzed retrospectively. RESULTS:Seventy-nine patients were enrolled in Standard group and 87 patients in Escalation group. Comparison between these groups demonstrated that Escalation group had fewer patients who discontinued treatment (p=0.001) and a lower incidence of headache (p=0.004). CONCLUSION:This type of dose escalation regimen of cilostazol may be superior to the standard regimen in tolerability.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:Endothelial-neutrophil adhesion is crucial for vascular injury, the major cause of diabetic vascular complications. On the other hand, platelet aggregation inhibitors, frequently used for diabetic patients with intermittent claudication, have been shown to decrease the incidence of atherosclerosis-mediated diseases (acute myocardial infarction and stroke). However, whether these agents act directly on the endothelial reactions to hyperglycemia remains unclear. Therefore, we examined their direct effects on endothelial-neutrophil adhesion and expression of endothelial adhesion molecules induced by high glucose. METHODS AND RESULTS:After human endothelial cells were cultured in high glucose medium, neutrophils from healthy volunteers were added and allowed to adhere for 30 min. Adhered neutrophils were quantified by measuring their myeloperoxidase (MPO) activities, and surface expression of endothelial adhesion molecules was determined with an enzyme immunoassay. Of the platelet aggregation inhibitors tested, only cilostazol significantly attenuated the adhesion through decreasing expression of intercellular adhesion molecule-1 (ICAM-1) and P-selectin. In addition, nitric oxide (NO) synthase inhibitors reduced the inhibitory effects of cilostazol, but a protein kinase C (PKC) activator did not. CONCLUSIONS:Cilostazol may act directly on endothelial cells to inhibit expression of adhesion molecules and neutrophil adhesion induced by high glucose through increasing NO production.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Cilostazol is a new phosphodiesterase inhibitor that suppresses platelet aggregation and also acts as a direct arterial vasodilator. This prospective, randomized, placebo-controlled, parallel-group clinical trial evaluated the efficacy of cilostazol for treatment of stable, moderately severe intermittent claudication.

METHODS AND RESULTS:Study inclusion criteria included age > or =40 years, initial claudication distance (ICD) on treadmill (12.5% incline, 3.2 km/h) between 30 and 200 m, and confirmation of diagnosis of chronic lower-extremity arterial occlusive disease. After stabilization and single-blind placebo lead-in, 81 subjects (62 male, 19 female) from 3 centers were randomized unequally (2:1) to 12 weeks of treatment with cilostazol 100 mg PO BID or placebo. Primary outcome measures included ICD and maximum distance walked (absolute claudication distance, or ACD). Secondary outcome measures included ankle pressures, subjective assessments of benefit by patients and physicians, and safety. Treatment and control groups were similar with respect to age, severity of symptoms, ankle pressures, and smoking status. Statistical analyses used intention-to-treat analyses for each of 77 subjects who had > or =1 treadmill test after initiation of therapy. Comparisons between groups were based on logarithms of ratios of ICD and ACD changes from baseline using ANOVA test at last treatment visit. The estimated treatment effect showed a 35% increase in ICD (P<0.01) and a 41% increase in ACD (P<0.01). There was no significant change in resting or postexercise ankle/brachial indexes. Patients' and physicians' subjective assessments corroborated the measured improvements in walking performance observed in the cilostazol-treated group.

CONCLUSIONS:Cilostazol improved walking distances, significantly increasing ICD and ACD. The data suggest cilostazol is safe and well tolerated for the treatment of intermittent claudication.

背景与目标： 背景 : 西洛他唑是一种新的磷酸二酯酶抑制剂，可抑制血小板聚集，还可作为直接的动脉血管扩张剂。这项前瞻性，随机，安慰剂对照，平行组临床试验评估了西洛他唑治疗稳定，中度重度间歇性跛行的疗效。
方法和结果 : 研究纳入标准包括年龄> 或 = 40岁，跑步机上的初始跛行距离 (ICD) (12.5% 倾斜，3.2千米/h) 在30至200 m之间，并确认诊断为慢性下肢动脉闭塞性疾病。在稳定和单盲安慰剂引导后，来自3个中心的81名受试者 (62名男性，19名女性) 被随机分配 (2:1) 至12周的西洛他唑100 mg PO BID或安慰剂治疗。主要结局指标包括ICD和最大步行距离 (绝对跛行距离，或ACD)。次要结局指标包括脚踝压力，患者和医生对获益的主观评估以及安全性。治疗组和对照组在年龄，症状严重程度，脚踝压力和吸烟状况方面相似。统计分析使用意向治疗分析，对77名受试者在开始治疗后进行> 或 = 1台跑步机测试。组间的比较基于最后一次治疗访视时使用ANOVA检验的ICD和ACD从基线变化的比率的对数。估计的治疗效果显示ICD 35% 增加 (P<0.01)，ACD 41% 增加 (P<0.01)。静息或运动后的踝/肱指数无明显变化。患者和医生的主观评估证实了在西洛他唑治疗组中观察到的步行性能的改善。
结论 : 西洛他唑改善了步行距离，显着增加了ICD和ACD。数据表明西洛他唑治疗间歇性跛行是安全且耐受性良好的。

BACKGROUND & AIMS: This study sought to evaluate the effect of cilostazol in preventing restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) in 68 patients35 patients received cilostazol immediately after PTCA and 33 patients received aspirin or ticlopidine. Repeat coronary angiography was performed 4 to 6 months after PTCA and the incidence of restenosis was significantly lower (17%) in the cilostazol group than in the non-cilostazol group (40%) (p < 0.05), which indicates that cilostazol has the potential to prevent restenosis after PTCA.

背景与目标： 本研究旨在评估68例患者成功经皮腔内冠状动脉成形术 (PTCA) 后西洛他唑预防再狭窄的效果。35例患者在PTCA后立即接受西洛他唑，33例患者接受阿司匹林或噻氯匹定。PTCA术后4 ~ 6个月再次行冠状动脉造影，再狭窄发生率 (17%) 西洛他唑组明显低于非西洛他唑组 (40%) (p <0.05)，这表明西洛他唑具有预防PTCA后再狭窄的潜力。