Objective To compare the effects of cilostazol on cerebral arteries and cerebrovascular blood flow in secondary prevention of ischemic stroke, with those of aspirin. Methods Sixty-eight patients who had ischemic strok...Objective To compare the effects of cilostazol on cerebral arteries and cerebrovascular blood flow in secondary prevention of ischemic stroke, with those of aspirin. Methods Sixty-eight patients who had ischemic stroke during the recent 1-6 months were recruited and randomized into cilostazol or aspirin group. Cerebrovascular condition was assessed by magnetic resonance angiography （MRA） and transcranial doppler ultrasonography （TCD） at the beginning of the study and after 12-month medication. Results During the clinical follow-up, ischemic stroke recurred in 2 patients in cilostazol group, while in aspirin group, one case of ischemic stroke recurrence and one case of acute myocardial infarction were found. MRA revealed that in aspirin group, the percentages of patients experiencing aggravation and attenuation of cerebrovascular condition were 3.3% and 6.7%, respectively, while in aspirin group, they were 3.3% and 10%, respectively. Moreover, TCD revealed that 26.9% of the patients in aspirin group and 14.3% of the patients in cilostazol group experienced aggravation of cerebrovascular condition. However, the systolic peak flow velocity of the previously abnormal arteries increased by 42.9% after 12-month medication of cilostazol, which was significantly higher than that after aspirin medication （27.5%） （P = 0.04）. Furthermore, as a major side effect of antiplatelet therapy, the frequrency of bleeding was much less in cilostazol group （0 case in cilostazol group vs 5 in aspirin, P 〈 0.05）. Conclusion Cilostazol is as effective as aspirin in preventing the aggravation of cerebral arteries in secondary prevention of ischemic stroke. Besides, it is more safe. Cilostazol can increase the systolic peak flow velocity of cerebral arteries, which may improve the blood supply of focal ischemia.展开更多
A simple,rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS） method has been developed for the simultaneous determination of cilostazol and its pharmacologically active m...A simple,rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS） method has been developed for the simultaneous determination of cilostazol and its pharmacologically active metabolite 3,4-dehydro cilostazol in human plasma using deuterated analogs as internal standards（ISs）.Plasma samples were prepared using solid phase extraction and chromatographic separation was performed on UPLC BEH C18（50 mm × 2.1 mm.1.7 μm） column.The method was established over a concentration range of 0.5-1000 ng/mL for cilostazol and 0.5-500 ng/mL for 3.4-dehydro cilostazol.Intra- and inter-batch precision（%CV） and accuracy for the analytes were found within 0.93-1.88 and 98.8-101.7% for cilostazol and 0.91-2.79 and 98.0-102.7% for the metabolite respectively.The assay recovery was within 95-97% for both the analytes and internal standards.The method was successfully applied to support a bioequivalence study of 100 mg cilostazol in30 healthy subjects.展开更多
Hypoxiainducible factor1 and its specific target gene heme oxygenase1, are involved in acute cerebral ischemia. However, very few studies have examined in detail the changes in the hy poxiainducible factor1/heme oxyge...Hypoxiainducible factor1 and its specific target gene heme oxygenase1, are involved in acute cerebral ischemia. However, very few studies have examined in detail the changes in the hy poxiainducible factor1/heme oxygenase1 signaling pathway in chronic cerebral ischemia. In this study, a rat model of chronic cerebral ischemia was established by permanent bilateral common carotid artery occlusion, and these rats were treated with intragastric cilostazol （30 mg/kg） for 9 weeks. Morris water maze results showed that cognitive impairment gradually worsened as the cerebral ischemia proceeded. Immunohistochemistry, semiquantitative PCR and western blot analysis showed that hypoxiainducible factorla and heme oxygenase1 expression levels in creased after chronic cerebral ischemia, with hypoxiainducible factorla expression peaking at 3 weeks and heme oxygenase1 expression peaking at 6 weeks. These results suggest that the elevated levels of hypoxiainducible factorla may upregulate heine oxygenase1 expression fol lowing chronic cerebral ischemia and that the hypoxiainducible factor1/heme oxygenase1 sig naling pathway is involved in the development of cognitive impairment induced by chronic cerebral ischemia. Cilostazol treatment alleviated the cognitive impairment in rats with chronic cerebral ischemia, decreased hypoxiainducible factorla and heme oxygenase1 expression levels, and reduced apoptosis in the frontal cortex. These findings demonstrate that cilostazol can protect against cognitive impairment induced by chronic cerebral ischemic injury through an antiapoptotic mechanism.展开更多
Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and indi...Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati- ents, 165 for per-protocol and 160 for the safety （QTc intervals） were set, respectively. Probucol significantly reduced total cholesterol （P 〈 0.001）, low-density lipoprotein cholesterol （LDL-C）, （P = 0.01）, and high-density lipoprotein cholesterol （HDL-C） （P 〈 0.001） compared with conventional therapy. Cilostazol was effective in increasing HDL-C （P = 0.002） and reducing triglycerides levels （P 〈 0.01） compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein （Ox-LDL, P = 0.065）. No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.展开更多
Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this be...Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mito-chondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arr-hythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore （mPTP） blocker, cyclosporine A （CsA）, and an inner membrane anion channel （IMAC） blocker, 4＇-chlorodiazepam （CDP）, were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species （ROS） production, mitochondrial membrane potential change and mi-tochondrial swelling were determined as indicators of cardiac mitochondrial function. Results Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS produc-tion. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of car-diac mitochondrial dysfunction caused by severe oxidative stress.展开更多
OBJeCTIve：To assess the efifcacy and safety of cilostazol on the progression and regression of symptomatic intracranial artery stenosis. DATA ReTRIvAL： We searched the main databases for eligible trials including Me...OBJeCTIve：To assess the efifcacy and safety of cilostazol on the progression and regression of symptomatic intracranial artery stenosis. DATA ReTRIvAL： We searched the main databases for eligible trials including Medline （from 1966 to June 2014）, Embase （from 1980 to June 2014）, Cochrane Library （Issue 6, 2014）, Chinese National Knowledge Infrastructure （from 1995 to June 2014）, Current Controlled Trials （http：//controlled-trials.com）, Clinical Trials.gov （http：//clinicaltrials.gov）, and Chinese Clinical Trial Registry （http：//www.chictr.org）. All studies regarding prevention and treatment of symptomatic intracranial arterial stenosis by cilostazol were collected. The Mesh or text keywords were the En-glish words： “cilostazol, phosphodiesterase 3 inhibitor, atherosclerosis, and ischemic stroke.” No restrictions were put on publications or publication language. SeLeCTION CRITeRIA：Grade A or B randomized controlled trials were selected according to the quality of evaluation criteria from the Cochrane Collaboration, in which cilostazol and aspi-rin were used to evaluate the effects of cilostazol in the treatment of patients with symptomatic intracranial artery stenosis. The quality of study methodology was evaluated based on criteria de-scribed in Cochrane Reviewer’s Handbook 5.0.1. RevMan 5.2 software was used for data analysis. MAIN OUTCOMe MeASUReS： Clinical efifcacy and safety of cilostazol in stopping progression and promoting regression of symptomatic intracranial artery stenosis were measured by magnet-ic resonance angiography and transcranial Doppler. ReSULTS：Two randomized controlled trials with a total of 203 patients were included in this study. The results showed that while cilostazol was associated with a significantly reduced progression of intracranial artery stenosis （OR = 0.21, 95%CI： 0.09–0.47,P 〈 0.01）, it had no beneifcial effect on symptom regression （OR = 1.42, 95%CI： 0.80–2.51,P = 0.24）. During the follow-up period, although some adverse effects developed, including headache, gastrointestinal disturbance, and dizziness, incidences of bleeding were lower than in aspirin-treated patients. CONCLUSION：Cilostazol may prevent the progression of symptomatic intracranial artery ste-nosis, which could reduce the incidence of ischemic stroke.展开更多
Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions Plasmacytoid dendritic cells （pDCs） have been found to participate in the progres...Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions Plasmacytoid dendritic cells （pDCs） have been found to participate in the progression of atherosclerosis mainly through interferon ct （IFN-ct） production. Whether cilostazol influences pDCs activation is still not clear. In this study, we aimed to investigate the effects of cilostazol on cell activation and antigen presentation ofpDCs in vitro in this study. Methods Peripheral blood mononuclear cells isolated by Ficoll cen- trifugation and pDCs sorted by flow cytometry were used in this study. After pretreated with cilostazol for 2 h, cells were stimulated with CpG-A, R848 or virus for 6 h or 20 h, or stimulated with CpG-B for 48 h and then co-cultured with naive T cell for five days. Cytokines in supernatant and intracellular cytokines were analyzed by ELISA or flow cytometry respectively. Results Our data indicated that cilostazol could inhibit IFN-α and tumor necrosis factor α （TNF-α） production from pDCs in a dose-dependent manner. In addition, the ability of priming na ve T cells of pDCs was also impaired by cilostazol. The inhibitory effect was not due to cell killing since the viability of pDCs did not change upon cilostazol treatment. Conclusion Cilostazol inhibits pDCs cell activation and antigen presentation in vitro, which may explain how cilostazol protects against atherosclerosis.展开更多
Cilostazol, a potent inhibitor of type 3 phosphodiesterase (PDE3), has recently been reported to exert neuroprotective effects during acute cerebral ischemic injury. These effects are, at least in part, mediated by th...Cilostazol, a potent inhibitor of type 3 phosphodiesterase (PDE3), has recently been reported to exert neuroprotective effects during acute cerebral ischemic injury. These effects are, at least in part, mediated by the inhibition of oxidative cell death. However, the effects of cilostazol on glucose metabolism in brain cells have not been determined. In the present study, we examined the effects of cilostazol on the oxidative metabolism of glucose and the resultant formation of reactive oxygen species (ROS) in cultured neurons and astroglia. Cultures of neurons or astroglia were prepared from Sprague-Dawley rats. The cells were treated with cilostazol (0 – 30 μM) for 48 hours prior to the assay. L-[U-14C]lactate ([14C]lactate) or [1-14C]pyruvate ([14C]pyruvate) oxidation was measured. ROS production was determined using an H2DCFDA assay with a microplate reader. Forty-eight hours of exposure to cilostazol resulted in dose-dependent increases in [14C]lactate and [14C]pyruvate oxidation in both the neurons and astroglia. Dibutyryl cyclic AMP (0 – 0.5 mM) also increased [14C]lactate oxidation, indicating cAMP-mediated PDH activation. In contrast, free radical formation was not affected by cilostazol in either the neurons or astroglia. Cilostazol enhanced the oxidative metabolism of glucose in both neurons and astroglia, while it did not augment ROS production.展开更多
Background Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activit...Background Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Recently, cilostazol has been used for antiplatelet therapy after coronary bare metal stent implantation for thrombosis and restenosis prevention. This prospective randomized and double blind trial was designed to investigate the safety and efficacy of cilostazol for the prevention of late restenosis and acute or subacute stent thrombosis. Methods One hundred and twenty patients who underwent elective stent were randomly assigned to treatment group with cilostazol 200 mg/d （n = 60）, clopidogrel 75 mg/d and aspirin 100 mg/d or to control group with clopidogrel treatment 75 mg/d （n = 60） and aspirin 100 mg/d. Follow-up coronary angiography was performed 6--9 months later. Results Nine months major adverse cardio-cerebral event （MACCE） were lower in treatment groups （P〈0.05）. The quantitative coronary angiography （QCA） at 6 months follow-up showed that minimum lumen diameter （MLD） was higher in treatment group than that of control group [（2.14 ± 0.52）mm vs （1.82 ± 0.36）mm, P〈0.05]. Late lumen loss （LL） [（0.82 ± 0.42）mm vs （1.31 ± 0.58）mm; P〈0.01 ], restenosis rate （RR） （14% vs 32%; P〈0.05） and target lesion revascularizaion （TLR） rate （5% vs 17%; P〈0.05） were lower in treatment group than in control group. Conclusion Cilostazol therapy is an effective regimen for prevention not only stent thrombosis but also RR and TLR through reducing MLD without the risk of increasing bleeding.展开更多
Diabetic nephropathy （DN） is the most common microvascular complication of diabetes and is one of the major causes of end-stage renal disease （ESRD）. Cilostazol, an antiplatelet drug, plays an important role in t...Diabetic nephropathy （DN） is the most common microvascular complication of diabetes and is one of the major causes of end-stage renal disease （ESRD）. Cilostazol, an antiplatelet drug, plays an important role in the prevention and treatment of the chronic complications of diabetes through a series of mechanisms, including anti-inflammation, the inhibition of vascular smooth muscle proliferation, the protection of nerve cells, and the regulation of blood lipids.展开更多
Background Stroke is one of the leading causes of death worldwide.Cilostazol,an antiplatelet and phosphodiesterase 3 inhibitor,has not been clearly established for ischaemic stroke use.We aim to determine the efficacy...Background Stroke is one of the leading causes of death worldwide.Cilostazol,an antiplatelet and phosphodiesterase 3 inhibitor,has not been clearly established for ischaemic stroke use.We aim to determine the efficacy and safety of cilostazol for secondary stroke prevention.Methods MEDLINE,EMBASE,Cochrane Library,Web of Science and ClinicalTrials.gov were searched from inception to 25 September 2020,for randomised trials comparing the efficacy and safety of cilostazol monotherapy or dual therapy with another antiplatelet regimen or placebo,in patients with ischaemic stroke.Version 2 of the Cochrane risk-of-bias tool for randomised trials(RoB 2)was used to assess study quality.This meta-analysis was reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)statement.Results Eighteen randomised trials comprising 11429 participants were included in this meta-analysis.Most trials possessed low risk of bias and were of low heterogeneity.Cilostazol significantly reduced the rate of ischaemic stroke recurrence(risk ratio,RR=0.69,95%CI 0.58 to 0.81),any stroke recurrence(RR=0.64,95%CI 0.54 to 0.74)and major adverse cardiovascular events(RR=0.67,95%CI 0.56 to 0.81).Cilostazol did not significantly decrease mortality(RR=0.90,95%CI 0.64 to 1.25)or increase the rate of good functional outcome(Modified Rankin Scale score of 0–1;RR=1.07,95%CI 0.95 to 1.19).Cilostazol demonstrated favourable safety profile,significantly reducing the risk of intracranial haemorrhage(RR=0.46,95%CI 0.31 to 0.68)and major haemorrhagic events(RR=0.49,95%CI 0.34 to 0.70).Conclusions Cilostazol demonstrated superior efficacy and safety profiles compared with traditional antiplatelet regimens such as aspirin and clopidogrel for secondary stroke prevention but does not appear to affect functional outcomes.Future randomised trials can be conducted outside East Asia,or compare cilostazol with a wider range of antiplatelet agents.展开更多
基金supported by the Science and Technology Planned Project of Bureau of Education of Guangzhou, China (No. 08A 002)the grant from Zhejiang Dazhong Pharmaceutical Company
文摘Objective To compare the effects of cilostazol on cerebral arteries and cerebrovascular blood flow in secondary prevention of ischemic stroke, with those of aspirin. Methods Sixty-eight patients who had ischemic stroke during the recent 1-6 months were recruited and randomized into cilostazol or aspirin group. Cerebrovascular condition was assessed by magnetic resonance angiography （MRA） and transcranial doppler ultrasonography （TCD） at the beginning of the study and after 12-month medication. Results During the clinical follow-up, ischemic stroke recurred in 2 patients in cilostazol group, while in aspirin group, one case of ischemic stroke recurrence and one case of acute myocardial infarction were found. MRA revealed that in aspirin group, the percentages of patients experiencing aggravation and attenuation of cerebrovascular condition were 3.3% and 6.7%, respectively, while in aspirin group, they were 3.3% and 10%, respectively. Moreover, TCD revealed that 26.9% of the patients in aspirin group and 14.3% of the patients in cilostazol group experienced aggravation of cerebrovascular condition. However, the systolic peak flow velocity of the previously abnormal arteries increased by 42.9% after 12-month medication of cilostazol, which was significantly higher than that after aspirin medication （27.5%） （P = 0.04）. Furthermore, as a major side effect of antiplatelet therapy, the frequrency of bleeding was much less in cilostazol group （0 case in cilostazol group vs 5 in aspirin, P 〈 0.05）. Conclusion Cilostazol is as effective as aspirin in preventing the aggravation of cerebral arteries in secondary prevention of ischemic stroke. Besides, it is more safe. Cilostazol can increase the systolic peak flow velocity of cerebral arteries, which may improve the blood supply of focal ischemia.
文摘A simple,rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS） method has been developed for the simultaneous determination of cilostazol and its pharmacologically active metabolite 3,4-dehydro cilostazol in human plasma using deuterated analogs as internal standards（ISs）.Plasma samples were prepared using solid phase extraction and chromatographic separation was performed on UPLC BEH C18（50 mm × 2.1 mm.1.7 μm） column.The method was established over a concentration range of 0.5-1000 ng/mL for cilostazol and 0.5-500 ng/mL for 3.4-dehydro cilostazol.Intra- and inter-batch precision（%CV） and accuracy for the analytes were found within 0.93-1.88 and 98.8-101.7% for cilostazol and 0.91-2.79 and 98.0-102.7% for the metabolite respectively.The assay recovery was within 95-97% for both the analytes and internal standards.The method was successfully applied to support a bioequivalence study of 100 mg cilostazol in30 healthy subjects.
基金supported by the Natural Science Fundation of Jilin Province in China, No.200705272
文摘Hypoxiainducible factor1 and its specific target gene heme oxygenase1, are involved in acute cerebral ischemia. However, very few studies have examined in detail the changes in the hy poxiainducible factor1/heme oxygenase1 signaling pathway in chronic cerebral ischemia. In this study, a rat model of chronic cerebral ischemia was established by permanent bilateral common carotid artery occlusion, and these rats were treated with intragastric cilostazol （30 mg/kg） for 9 weeks. Morris water maze results showed that cognitive impairment gradually worsened as the cerebral ischemia proceeded. Immunohistochemistry, semiquantitative PCR and western blot analysis showed that hypoxiainducible factorla and heme oxygenase1 expression levels in creased after chronic cerebral ischemia, with hypoxiainducible factorla expression peaking at 3 weeks and heme oxygenase1 expression peaking at 6 weeks. These results suggest that the elevated levels of hypoxiainducible factorla may upregulate heine oxygenase1 expression fol lowing chronic cerebral ischemia and that the hypoxiainducible factor1/heme oxygenase1 sig naling pathway is involved in the development of cognitive impairment induced by chronic cerebral ischemia. Cilostazol treatment alleviated the cognitive impairment in rats with chronic cerebral ischemia, decreased hypoxiainducible factorla and heme oxygenase1 expression levels, and reduced apoptosis in the frontal cortex. These findings demonstrate that cilostazol can protect against cognitive impairment induced by chronic cerebral ischemic injury through an antiapoptotic mechanism.
文摘Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati- ents, 165 for per-protocol and 160 for the safety （QTc intervals） were set, respectively. Probucol significantly reduced total cholesterol （P 〈 0.001）, low-density lipoprotein cholesterol （LDL-C）, （P = 0.01）, and high-density lipoprotein cholesterol （HDL-C） （P 〈 0.001） compared with conventional therapy. Cilostazol was effective in increasing HDL-C （P = 0.002） and reducing triglycerides levels （P 〈 0.01） compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein （Ox-LDL, P = 0.065）. No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.
文摘Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mito-chondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arr-hythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore （mPTP） blocker, cyclosporine A （CsA）, and an inner membrane anion channel （IMAC） blocker, 4＇-chlorodiazepam （CDP）, were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species （ROS） production, mitochondrial membrane potential change and mi-tochondrial swelling were determined as indicators of cardiac mitochondrial function. Results Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS produc-tion. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of car-diac mitochondrial dysfunction caused by severe oxidative stress.
文摘OBJeCTIve：To assess the efifcacy and safety of cilostazol on the progression and regression of symptomatic intracranial artery stenosis. DATA ReTRIvAL： We searched the main databases for eligible trials including Medline （from 1966 to June 2014）, Embase （from 1980 to June 2014）, Cochrane Library （Issue 6, 2014）, Chinese National Knowledge Infrastructure （from 1995 to June 2014）, Current Controlled Trials （http：//controlled-trials.com）, Clinical Trials.gov （http：//clinicaltrials.gov）, and Chinese Clinical Trial Registry （http：//www.chictr.org）. All studies regarding prevention and treatment of symptomatic intracranial arterial stenosis by cilostazol were collected. The Mesh or text keywords were the En-glish words： “cilostazol, phosphodiesterase 3 inhibitor, atherosclerosis, and ischemic stroke.” No restrictions were put on publications or publication language. SeLeCTION CRITeRIA：Grade A or B randomized controlled trials were selected according to the quality of evaluation criteria from the Cochrane Collaboration, in which cilostazol and aspi-rin were used to evaluate the effects of cilostazol in the treatment of patients with symptomatic intracranial artery stenosis. The quality of study methodology was evaluated based on criteria de-scribed in Cochrane Reviewer’s Handbook 5.0.1. RevMan 5.2 software was used for data analysis. MAIN OUTCOMe MeASUReS： Clinical efifcacy and safety of cilostazol in stopping progression and promoting regression of symptomatic intracranial artery stenosis were measured by magnet-ic resonance angiography and transcranial Doppler. ReSULTS：Two randomized controlled trials with a total of 203 patients were included in this study. The results showed that while cilostazol was associated with a significantly reduced progression of intracranial artery stenosis （OR = 0.21, 95%CI： 0.09–0.47,P 〈 0.01）, it had no beneifcial effect on symptom regression （OR = 1.42, 95%CI： 0.80–2.51,P = 0.24）. During the follow-up period, although some adverse effects developed, including headache, gastrointestinal disturbance, and dizziness, incidences of bleeding were lower than in aspirin-treated patients. CONCLUSION：Cilostazol may prevent the progression of symptomatic intracranial artery ste-nosis, which could reduce the incidence of ischemic stroke.
文摘Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions Plasmacytoid dendritic cells （pDCs） have been found to participate in the progression of atherosclerosis mainly through interferon ct （IFN-ct） production. Whether cilostazol influences pDCs activation is still not clear. In this study, we aimed to investigate the effects of cilostazol on cell activation and antigen presentation ofpDCs in vitro in this study. Methods Peripheral blood mononuclear cells isolated by Ficoll cen- trifugation and pDCs sorted by flow cytometry were used in this study. After pretreated with cilostazol for 2 h, cells were stimulated with CpG-A, R848 or virus for 6 h or 20 h, or stimulated with CpG-B for 48 h and then co-cultured with naive T cell for five days. Cytokines in supernatant and intracellular cytokines were analyzed by ELISA or flow cytometry respectively. Results Our data indicated that cilostazol could inhibit IFN-α and tumor necrosis factor α （TNF-α） production from pDCs in a dose-dependent manner. In addition, the ability of priming na ve T cells of pDCs was also impaired by cilostazol. The inhibitory effect was not due to cell killing since the viability of pDCs did not change upon cilostazol treatment. Conclusion Cilostazol inhibits pDCs cell activation and antigen presentation in vitro, which may explain how cilostazol protects against atherosclerosis.
文摘Cilostazol, a potent inhibitor of type 3 phosphodiesterase (PDE3), has recently been reported to exert neuroprotective effects during acute cerebral ischemic injury. These effects are, at least in part, mediated by the inhibition of oxidative cell death. However, the effects of cilostazol on glucose metabolism in brain cells have not been determined. In the present study, we examined the effects of cilostazol on the oxidative metabolism of glucose and the resultant formation of reactive oxygen species (ROS) in cultured neurons and astroglia. Cultures of neurons or astroglia were prepared from Sprague-Dawley rats. The cells were treated with cilostazol (0 – 30 μM) for 48 hours prior to the assay. L-[U-14C]lactate ([14C]lactate) or [1-14C]pyruvate ([14C]pyruvate) oxidation was measured. ROS production was determined using an H2DCFDA assay with a microplate reader. Forty-eight hours of exposure to cilostazol resulted in dose-dependent increases in [14C]lactate and [14C]pyruvate oxidation in both the neurons and astroglia. Dibutyryl cyclic AMP (0 – 0.5 mM) also increased [14C]lactate oxidation, indicating cAMP-mediated PDH activation. In contrast, free radical formation was not affected by cilostazol in either the neurons or astroglia. Cilostazol enhanced the oxidative metabolism of glucose in both neurons and astroglia, while it did not augment ROS production.
文摘Background Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Recently, cilostazol has been used for antiplatelet therapy after coronary bare metal stent implantation for thrombosis and restenosis prevention. This prospective randomized and double blind trial was designed to investigate the safety and efficacy of cilostazol for the prevention of late restenosis and acute or subacute stent thrombosis. Methods One hundred and twenty patients who underwent elective stent were randomly assigned to treatment group with cilostazol 200 mg/d （n = 60）, clopidogrel 75 mg/d and aspirin 100 mg/d or to control group with clopidogrel treatment 75 mg/d （n = 60） and aspirin 100 mg/d. Follow-up coronary angiography was performed 6--9 months later. Results Nine months major adverse cardio-cerebral event （MACCE） were lower in treatment groups （P〈0.05）. The quantitative coronary angiography （QCA） at 6 months follow-up showed that minimum lumen diameter （MLD） was higher in treatment group than that of control group [（2.14 ± 0.52）mm vs （1.82 ± 0.36）mm, P〈0.05]. Late lumen loss （LL） [（0.82 ± 0.42）mm vs （1.31 ± 0.58）mm; P〈0.01 ], restenosis rate （RR） （14% vs 32%; P〈0.05） and target lesion revascularizaion （TLR） rate （5% vs 17%; P〈0.05） were lower in treatment group than in control group. Conclusion Cilostazol therapy is an effective regimen for prevention not only stent thrombosis but also RR and TLR through reducing MLD without the risk of increasing bleeding.
文摘Diabetic nephropathy （DN） is the most common microvascular complication of diabetes and is one of the major causes of end-stage renal disease （ESRD）. Cilostazol, an antiplatelet drug, plays an important role in the prevention and treatment of the chronic complications of diabetes through a series of mechanisms, including anti-inflammation, the inhibition of vascular smooth muscle proliferation, the protection of nerve cells, and the regulation of blood lipids.
文摘Background Stroke is one of the leading causes of death worldwide.Cilostazol,an antiplatelet and phosphodiesterase 3 inhibitor,has not been clearly established for ischaemic stroke use.We aim to determine the efficacy and safety of cilostazol for secondary stroke prevention.Methods MEDLINE,EMBASE,Cochrane Library,Web of Science and ClinicalTrials.gov were searched from inception to 25 September 2020,for randomised trials comparing the efficacy and safety of cilostazol monotherapy or dual therapy with another antiplatelet regimen or placebo,in patients with ischaemic stroke.Version 2 of the Cochrane risk-of-bias tool for randomised trials(RoB 2)was used to assess study quality.This meta-analysis was reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)statement.Results Eighteen randomised trials comprising 11429 participants were included in this meta-analysis.Most trials possessed low risk of bias and were of low heterogeneity.Cilostazol significantly reduced the rate of ischaemic stroke recurrence(risk ratio,RR=0.69,95%CI 0.58 to 0.81),any stroke recurrence(RR=0.64,95%CI 0.54 to 0.74)and major adverse cardiovascular events(RR=0.67,95%CI 0.56 to 0.81).Cilostazol did not significantly decrease mortality(RR=0.90,95%CI 0.64 to 1.25)or increase the rate of good functional outcome(Modified Rankin Scale score of 0–1;RR=1.07,95%CI 0.95 to 1.19).Cilostazol demonstrated favourable safety profile,significantly reducing the risk of intracranial haemorrhage(RR=0.46,95%CI 0.31 to 0.68)and major haemorrhagic events(RR=0.49,95%CI 0.34 to 0.70).Conclusions Cilostazol demonstrated superior efficacy and safety profiles compared with traditional antiplatelet regimens such as aspirin and clopidogrel for secondary stroke prevention but does not appear to affect functional outcomes.Future randomised trials can be conducted outside East Asia,or compare cilostazol with a wider range of antiplatelet agents.
