MedWorm: Cilostazol

Control of cilostazol release kinetics and direction from a stent using a reservoir-based design.

Biomed Res — Sat, 28 Jan 2012 05:00:00 +0100

Authors: Parker T, Davé V, Falotico R, Zhao J, Nguyen T, He S, Sun YP, Rogers C Abstract Sustained release formulations of a potent antithrombotic drug, cilostazol, in poly-(lactic acid-co-glycolic acid) (PLGA) matrices were created for luminal release from a novel drug-eluting stent utilizing reservoirs (RES TECHNOLOGY™). The crystallinity of cilostazol and the morphology of the cilostazol/polymer matrix in the stent reservoirs were examined by cross-polarized optical microscopy and differential scanning calorimetry. An in vitro method was developed to study release kinetics of various cilostazol formulations and to examine correlation with in vivo release. Formulation parameters such as drug-to-polymer ratio and the use of a polymer barrier on the abluminal surface of the drug...

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Cilostazol suppression of arterial intimal hyperplasia is associated with decreased expression of sialyl Lewis X homing receptors on mononuclear cells and E-selectin in endothelial cells

Journal of Vascular Surgery — Fri, 27 Jan 2012 11:25:14 +0100

Conclusions: These results demonstrate that the protective effect of cilostazol against neointimal hyperplasia may be mediated by its anti-inflammatory actions of mononuclear cells homing to endothelial cells by decreasing SLX and E-selectin expression. Clinical Relevance: It is reported that cilostazol inhibits neointimal hyperplasia by decreasing the expression of some cell-adhesion molecules. We evaluated the effects of cilostazol for the expression of sialyl Lewis X (SLX) on mononuclear cells and E-selectin on endothelial cells, which interaction is the first step of inflammation action. Cilostazol was thought to show the anti-inflammatory actions by decreasing SLX and E-selectin expression in addition to decreasing the expression of some cell-adhesion molecules. (Source: Journal of...

Ginkgo bilobaExtract(GbE) Enhances the Anti-atherogenic Effect of Cilostazol by InhibitingROS Generation.

Atherosclerosis — Fri, 27 Jan 2012 05:00:00 +0100

In this study, the synergistic effect of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and Ginkgo biloba extract (GbE) was examined in apolipoprotein E (ApoE) null mice. Co-treatment withGbE and cilostazol synergistically decreased reactive oxygen species (ROS) production in ApoE null mice fed a high-fat diet. Co-treatment resulted in a significantly decreased atherosclerotic lesion area compared to untreated ApoE mice. The inflammatory cytokines and adhesion moleculessuch as monocyte chemoattractant-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and VCAM-1which can initiateatherosclerosiswere significantly reduced by the co-treatment of cilostazol withGbE. Further, the infiltration of macrophages into the intima was decreased by co...

Quantitative assessment of changes in carotid plaques during cilostazol administration using three-dimensional ultrasonography and non-gated magnetic resonance plaque imaging

Neuroradiology — Tue, 24 Jan 2012 06:50:06 +0100

Conclusions 3D-US and MR plaque imaging can quantitatively detect changes in the size and composition of carotid plaques during cilostazol therapy. Content Type Journal ArticleCategory Diagnostic NeuroradiologyPages 1-7DOI 10.1007/s00234-012-1011-2Authors Mao Yamaguchi, Department of Neurology and Gerontology, Iwate Medical University, 19-1 Uchimaru, Morioka, JapanMakoto Sasaki, Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, 19-1 Uchimaru, Morioka, JapanHideki Ohba, Department of Neurology and Gerontology, Iwate Medical University, 19-1 Uchimaru, Morioka, JapanKiyofumi Mori, Department of Neurology and Gerontology, Iwate Medical University, 19-1 Uchimaru, Morioka, JapanShinsuke Narumi, Department of Neurology and Geronto...

Current Evidence for Antithrombotic Therapy after Peripheral Vascular Interventions.

Current Vascular Pharmacology — Fri, 20 Jan 2012 05:00:00 +0100

Authors: Saha SP, Whayne TF, Mukherjee D Abstract There is occurring a progressive increase in peripheral arterial disease (PAD) in the United States and around the World. This is undoubtedly associated with deterioration in health status and an increase in cardiovascular risk factors. There are multiple old and new antithrombotic and anticoagulation medications that have been used for the treatment of PAD. Several are considered in this review. The purpose of antithrombotics in surgery is the prevention of thrombosis of surgical bypass grafts in order to help maintain their patency. Multiple different medication approaches can be made in association with surgery. Just as in the case of peripheral vascular surgery, thrombosis also plagues the long-term maintenance of patency follow...

Options to Overcome Clopidogrel Response Variability.

Circulation Journal — Thu, 12 Jan 2012 05:00:00 +0100

Authors: Park KW, Kim HS Abstract Oral antiplatelet agents targeting the platelet P2Y12 receptor are an integral component of treating patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. Clopidogrel has been the most commonly used agent in this respect worldwide. However, there are certain shortcomings of clopdiogrel, the most important of which is the wide response variability of platelet inhibition. The response to clopidogrel is affected by various clinical variables, genetic variations involved in its activation, and drug-drug interactions. Therefore, clinicians are faced with challenges in situations where high inhibition of platelets is necessary and in cases where the response to clopidogrel may be suboptimal. There are various ways...

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Platelet Reactivity in CKD - Cilostazol vs ClopidogrelPlatelet Reactivity in CKD - Cilostazol vs Clopidogrel

Medscape Today Headlines — Thu, 05 Jan 2012 04:00:00 +0100

Learn more about functional impact of cilostazol on platelets in CKD patients undergoing hemodialysis. American Heart Journal (Source: Medscape Today Headlines)

Adjunctive pharmacotherapies for intermittent claudication--NICE guidance

Heart — Fri, 23 Dec 2011 05:00:00 +0100

There are a number of adjunctive pharmacotherapies available for individuals with peripheral arterial disease and intermittent claudication, in whom appropriate risk factor modification and antiplatelet treatment have been initiated. These include cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, which have vasodilatation among their mechanisms of action and have been the subject of recent technology appraisal guidance offered by the National Institute for Health and Clinical Excellence (NICE).1 The guidance offered was based upon systematic review, meta-analysis and cost-effectiveness analysis and is summarised in box 1. Box 1Summary of NICE guidelines1 For individuals with peripheral arterial disease and intermittent claudication, where vasodilator treatment is c...

Systematic review and economic evaluation: Cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for treatment of intermittent claudication

NeLM - Drug Specific Reviews — Thu, 15 Dec 2011 05:00:00 +0100

Source: Health Technology Assessment (HTA) Area: Evidence > Drug Specific Reviews This systematic review conducted by researchers with the NHS Health Technology Assessment (HTA) programme examined the clinical- and cost-effectiveness of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no vasoactive drugs, for intermittent claudication in people with peripheral arterial disease whose symptoms continue despite a period of conventional management. A search for literature carried out between April to June 2010 identified 26 RCTs that met the inclusion criteria for the clinical effectiveness review. The following findings were reported: . There was evidence that walking distance outcomes were significantly improved by both ...

Cilostazol, a phosphodiesterase inhibitor, prevents no-reflow and hemorrhage in mice with focal cerebral ischemia.

Experimental Neurology — Thu, 08 Dec 2011 05:00:00 +0100

CONCLUSIONS: Cilostazol may possess protective properties against cerebral ischemic injury by preventing no-reflow and hemorrhagic transformation, via maintenance of microvascular integrity. PMID: 22173318 [PubMed - as supplied by publisher] (Source: Experimental Neurology)

Cilostazol improves clopidogrel platelet inhibitory effect in CKD patients

MedWire News - Cardiology — Wed, 07 Dec 2011 02:42:16 +0100

Adding cilostazol to antiplatelet therapy improves platelet inhibition in patients with chronic kidney disease undergoing hemodialysis, research shows. (Source: MedWire News - Cardiology)

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A selective phosphodiesterase 3 inhibitor rescues low PO2-induced ATP release from erythrocytes of humans with type 2 diabetes: implication for vascular control

AJP: Heart and Circulatory Physiology — Mon, 05 Dec 2011 05:00:00 +0100

Erythrocytes, via release of ATP in areas of low oxygen (O2) tension, are components of a regulatory system for the distribution of perfusion in skeletal muscle ensuring optimal O2 delivery to meet tissue needs. In type 2 diabetes (DM2), there are defects in O2 supply to muscle as well as a failure of erythrocytes to release ATP. The goal of this study was to ascertain if a phosphodiesterase 3 (PDE3) inhibitor, cilostazol, would rescue low O2-induced ATP release from DM2 erythrocytes and, thereby, enable these cells to dilate isolated erythrocyte-perfused skeletal muscle arterioles exposed to decreased extraluminal O2. Erythrocytes were obtained from healthy humans (HH; n = 12) and humans with DM2 (n = 17). We determined that 1) PDE3B is similarly expressed in both groups, 2) mastoparan 7 ...

Pharmacokinetic Comparison of Sustained- and Immediate-Release Oral Formulations of Cilostazol in Healthy Korean Subjects: A Randomized, Open-Label, 3-Part, Sequential, 2-Period, Crossover, Single-Dose, Food-Effect, and Multiple-Dose Study.

Clinical Therapeutics — Mon, 28 Nov 2011 05:00:00 +0100

CONCLUSIONS: These findings suggest that in this select group of healthy Korean volunteers, the SR formulation of cilostazol was not significantly different in AUC compared with that of the IR formulation, although it did display a significantly lower C(max) per dose in both the single- and multiple-dose groups. Food significantly increased the bioavailability of the SR formulation. The cilostazol SR and IR formulations were well tolerated in all parts of the study, with no serious adverse events reported. ClinicalTrials.gov identifier: NCT01455558. PMID: 22129569 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)

A phase II dose-ranging study of the phosphodiesterase inhibitor K-134 in patients with peripheral artery disease and claudication

Journal of Vascular Surgery — Mon, 28 Nov 2011 05:00:00 +0100

Conclusions: K-134 was generally well tolerated. K-134 at a dose of 100 mg twice daily did not affect PWT according to the primary analysis, but K-134 and cilostazol both increased PWT when analyzed using a mixed-effects model and in the per-protocol population. (Source: Journal of Vascular Surgery)

Novel Antiplatelet Therapies

Current Atherosclerosis Reports — Fri, 18 Nov 2011 17:29:28 +0100

Abstract Advances in antiplatelet therapy have significantly improved outcomes in patients with ischemic heart disease. Thienopyridines remain a cornerstone of therapy along with aspirin. Recently, concerns have been raised about the use of clopidogrel due to its pharmacokinetic and pharmacogenetic interpatient variability. A third-generation thienopyridine, prasugrel, overcomes some of these problems by improving inhibition of platelet aggregation, but increasing the risk of peri-procedural bleeding. Other novel antiplatelet agents, such as ticagrelor, have shown improved efficacy in recent trials and require further investigations. The field of pharmacotherapy continues to rapidly evolve as newer agents, such as thrombin receptor antagonists, along with older agents, suc...

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Platelet reactivity in patients with chronic kidney disease receiving adjunctive cilostazol compared with a high-maintenance dose of clopidogrel: Results of the Effect of Platelet Inhibition According to Clopidogrel Dose in Patients with Chronic Kidney Disease (PIANO-2 CKD) randomized study

American Heart Journal — Thu, 10 Nov 2011 05:00:00 +0100

Conclusions: Adjunctive cilostazol improves platelet inhibition compared with 75 or 150 mg of clopidogrel in CKD patients undergoing hemodialysis. (Source: American Heart Journal)

Novel agents for anti-platelet therapy

Journal of Hematology and Oncology — Fri, 04 Nov 2011 04:00:00 +0100

Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban) have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12) receptor...

Long-term results of direct and indirect endovascular revascularization based on the angiosome concept in patients with critical limb ischemia presenting with isolated below-the-knee lesions

Journal of Vascular Surgery — Thu, 03 Nov 2011 04:00:00 +0100

Conclusion: Achieving direct flow by angioplasty based on the angiosome concept in CLI patients with isolated BTK lesions is clinically important for AFS and freedom from MA and MALE. Limb salvage factors appear to differ between patients with and without direct flow from the feeding artery after EVT. (Source: Journal of Vascular Surgery)

Cilostazol Reduces the Risk of Hemorrhagic Infarction After Administration of Tissue-Type Plasminogen Activator in a Murine Stroke Model.

Stroke — Thu, 27 Oct 2011 04:00:00 +0100

CONCLUSIONS: Our results suggest that patients treated with cilostazol before onset of stroke could have a lower risk of cerebral hemorrhage after thrombolytic therapy and might also have a longer therapeutic time window for thrombolysis. Furthermore, the risk of cerebral hemorrhage can be significantly altered by prestroke therapies, and analysis of the effects of multiple drugs on tissue-type plasminogen activator-induced cerebral hemorrhage in animal models is essential for the extending safe and effective thrombolytic therapy to a wider group of patients. PMID: 22033992 [PubMed - as supplied by publisher] (Source: Stroke)

Drug-Drug Interactions Associated with Antiplatelet Therapy.

Current Pharmaceutical Biotechnology — Wed, 26 Oct 2011 04:00:00 +0100

Authors: Dunn SP, Macaulay TE Abstract Antiplatelet therapy is of paramount importance in the treatment and prevention of adverse cardiovascular events and stroke. Drug-drug interactions (DDIs) among antiplatelet therapies have been growing in both prevalence and clinical importance. Most DDIs with antiplatelet therapies are pharmacodynamic in nature. DDIs with thienopyridines and proton pump inhibitors have resulted in advisories from regulatory agencies although the full significance of this interaction is unknown. Other DDIs with thienopyridines may potentially exist with statins, calcium channel blockers, and warfarin but lack demonstratable evidence of harm. Aspirin may interact with a variety of medications, including non-steroidal anti-inflammatory agents and angiotensin inh...

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Interaction analysis between genetic polymorphisms and pharmacodynamic effect in patients treated with adjunctive cilostazol to dual antiplatelet therapy

British Journal of Clinical Pharmacology — Sat, 22 Oct 2011 05:35:06 +0100

CONCLUSION ‐ Among PCI‐treated patients, the effect of triple antiplatelet therapy is influenced by the CYP2C19 LOF allele. Its clinical benefit needs to be validated according to the CYP2C19 metabolic phenotype in future clinical trials. [Adjunctive Cilostazol Versus High Maintenancedose ClopidogrEL in Acute Myocardial Infarction Patients According to CYP2C19 Polymorphism (ACCEL‐AMI‐2C19); NCT00915733; and Adjunctive Cilostazol Versus High Maintenance‐dose Clopidogrel According to Cytochrome 2C19 Polymorphism (ACCEL‐2C19); NCT01012193]. (Source: British Journal of Clinical Pharmacology)

Cilostazol combined with aspirin prevents early neurological deterioration in patients with acute ischemic stroke: A pilot study

Journal of the Neurological Sciences — Thu, 20 Oct 2011 04:00:00 +0100

Abstract: Recent randomized trials have shown that cilostazol is superior to aspirin for secondary stroke prevention. We hypothesized that combining cilostazol with aspirin is more effective than aspirin alone in patients with acute ischemic stroke. This randomized study compared the effects of oral aspirin alone to aspirin plus cilostazol in patients with non-cardioembolic ischemic stroke within 48h of stroke onset. NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were checked before and after 14days and 6months of drug administration. The primary and secondary endpoints were neurological deterioration or stroke recurrence (NIHSS score≥1) within 14days and 6months, respectively. For statistical analysis, on-treatment analysis was conducted. Seventy-six patients were enrol...

Effect of cilostazol on the progression of carotid intima-media thickness: A meta-analysis of randomized controlled trials

Atherosclerosis — Wed, 19 Oct 2011 04:00:00 +0100

Abstract: Background: It has been well established that cilostazol has anti-proliferative effect against in-stent restenosis. However, it remains unclear whether cilostazol can prevent the progression of carotid atherosclerosis.Methods and results: We performed a meta-analysis of all relevant randomized controlled trials (RCTs) to evaluate the effect of cilostazol on the progression of carotid intima-media thickness (IMT). Five RCTs with 698 patients [597 subjects with type 2 diabetes mellitus (T2DM)] were included in this study. Cilostazol was associated with a significant reduction in the progression of carotid IMT (WMD, −0.08mm, 95% CI −0.13, −0.04; P=0.00003). Subgroup analysis shows that cilostazol monotherapy or addition to dual antiplatelet therapy (aspirin and clopidogrel) wa...

Cilostazol in Diabetic Neuropathy: Premature Farewell or New Beginning?

Angiology — Tue, 11 Oct 2011 04:00:00 +0100

Peripheral neuropathy remains a major chronic complication of diabetes mellitus. Its pathogenesis mainly involves chronic glucose toxicity and nerve ischemia. Preclinical studies have shown that cilostazol, a reversible selective inhibitor of phosphodiesterase-3A with antiplatelet, antithrombotic, and vasodilatory properties, exerts beneficial effects on nerve function in experimental diabetes. Clinical data, however, is sparse. Two recent randomized placebo-controlled clinical trials showed that cilostazol did not improve diabetic neuropathy in humans. Hence, more data is needed to confirm or refute the poor clinical efficacy of cilostazol. Importantly, future studies should include larger patient series, provide longer follow-up data, and employ more accurate diagnostic tools. (Source: A...

Cilostazol: A Pilot Study on Safety and Clinical Efficacy in Neuropathies of Diabetes Mellitus Type 2 (ASCEND)

Angiology — Tue, 11 Oct 2011 04:00:00 +0100

Conclusion: Despite significant improvement in the neuropathy symptom scores in the overall motor and sensory categories of the 3 arms of the study from baseline to week 12, no significant differences were found among the groups, indicating nonsuperiority of cilostazol in regard to improvement of neuropathy symptoms over the short study span. However, cilostazol, at low dose, was effective in improving walking speed from baseline to week 12, implying an improved blood flow. No significant worsening nor improvement in motor and sensory nerve conduction parameters were observed, comparing the 3 study arms from baseline to weeks 4, 12, and 16, supporting cilostazol’s safety. Overall, the adverse events of the 3 study arms did not significantly differ, and neither were there serious adve...

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Cilostazol to Overcome High On-Treatment Platelet Reactivity in Korean Patients Treated With Clopidogrel and Calcium-Channel Blocker.

Circulation Journal — Wed, 05 Oct 2011 04:00:00 +0100

Authors: Jeong YH, Tantry US, Bliden KP, Gurbel PA PMID: 21970840 [PubMed - as supplied by publisher] (Source: Circulation Journal)

Carbamazepine/cilostazol/omeprazole interaction: First report of an interaction, leading to fatal toxic epidermal necrolysis in an elderly patient: case report

Reactions — Mon, 03 Oct 2011 06:00:13 +0100

(Source: Reactions)

Representative images of left ventricular myocytes from Wistar Kyoto (WKY, left) and spontaneously hypertensive rats (SHR, right) labelled with antibodies raised against the calcium-ATPase SERCA2a (red) and the sarcolemmal sodium-calcium exchanger (NCX, green). See Ward et al., pp 711-716.

Clinical and Experimental Pharmacology and Physiology — Sat, 01 Oct 2011 04:00:00 +0100

Authors: Abstract Cover image: Representative images of left ventricular myocytes from Wistar Kyoto (WKY, left) and spontaneously hypertensive rats (SHR, right) labelled with antibodies raised against the calcium-ATPase SERCA2a (red) and the sarcolemmal sodium-calcium exchanger (NCX, green). See Ward et al., pp 711-716. • Cilostazol reduces myocardial infarct size • HF enhances PV arrhythmogenesis • NOS in simulated microgravity • Fasudil exerts antioxidant effects • Losartan diminishes schistosomal liver fibrosis • Proceedings of the Australian Physiological Society Symposium: Stress, disease and Ca -2+ management: The cardiovascular challenge. PMID: 21951297 [PubMed - in process] (Source: Clinical and Experimental Pharmacology and Physiology)

Are threshold levels of signal transduction required for the protective effect of cilostazol against cardiac ischaemia-reperfusion injury?

Clinical and Experimental Pharmacology and Physiology — Sat, 01 Oct 2011 04:00:00 +0100

Authors: Reis F PMID: 21711382 [PubMed - in process] (Source: Clinical and Experimental Pharmacology and Physiology)

Cilostazol Versus Aspirin for Secondary Prevention of Vascular Events After Stoke of Arterial Origin

Journal of Vascular Surgery — Sat, 01 Oct 2011 04:00:00 +0100

Conclusion: In Asian populations after an initial stroke, cilostazol is superior to aspirin in secondary prevention of stroke, myocardial infarction, or vascular death. Summary: This is a summary of a Cochrane Review. The review is based on the fact that aspirin for secondary prevention after stroke of arterial origin has been widely studied and prescribed. Cilostazol has been used for secondary prevention in Asian populations with non-cardioembolic stroke and no clinically evident cardiac disease. The purpose of this review was to determine the relative effectiveness and safety of cilostazol compared with aspirin in the prevention of stroke and other vascular events in patients with a previous transient ischemic attack (TIA) or ischemic stroke of arterial origin. (Source: Journal of Vasc...

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Use of prasugrel in a patient with clopidogrel hypersensitivity.

The Annals of Pharmacotherapy — Sat, 01 Oct 2011 04:00:00 +0100

CONCLUSIONS: Prasugrel may be considered a therapeutic alternative in some patients allergic or intolerant to clopidogrel, but additional data are warranted to make a strong conclusion. PMID: 21896923 [PubMed - in process] (Source: The Annals of Pharmacotherapy)

[Interims analysis of a prospective observational study on the use of cilostazol (pletal®) in daily clinical vascularsurgical practice].

Zentralblatt fur Chirurgie — Sat, 01 Oct 2011 04:00:00 +0100

CONCLUSION: Cilostazol medication can be considered a suitable tool as: (i) an initial step in the sequential therapeutic algorithm in stage II b of PAOD, (ii) a therapeutic alternative in exhausted vascular surgical (interventional) options. Further study-based clinical observations on the use of Cilostazol appear to be indicated. PMID: 22009542 [PubMed - in process] (Source: Zentralblatt fur Chirurgie)

[Vagal stimulation - a new possibility for conservative treatment of peripheral arterial occlusion disease].

Zentralblatt fur Chirurgie — Sat, 01 Oct 2011 04:00:00 +0100

CONCLUSION: The considerable increase in pain-free walking distance after vagal stimulation therapy by P-STIM is appreciably better than those which were described for supervised exercise therapy or pharmacotherapy with Naftidrofuryl or Cilostazol. On the basis of these results we think that vagal stimulation by P-STIM might be a new option for treating intermittent claudication. PMID: 22009541 [PubMed - in process] (Source: Zentralblatt fur Chirurgie)

Efficacy and safety of combination antiplatelet therapies in patients with symptomatic intracranial atherosclerotic stenosis.

Stroke — Fri, 30 Sep 2011 21:39:02 +0100

CONCLUSIONS: This trial failed to show significant difference in preventing progression of ICAS and new ischemic lesions between the 2 combination antiplatelet therapies in the patients with symptomatic ICAS. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00130039. PMID: 21799173 [PubMed - in process] (Source: Stroke)

Loading solution prevents activation damage of human platelets before lyophilization.

Cryobiology — Fri, 16 Sep 2011 04:00:00 +0100

Authors: Zhou J, Zhang C, Liu J, Fan L, Yang L Abstract The current study aims to optimize the compositions of platelet activation-inhibitors for a loading solution of lyophilizing protectants and to establish a series of perfect pretreatment methods for platelet lyophilization. The optimal combination of six kinds of inhibitors and loading solutions of lyophilizing protectants, including prostaglandin E1 (PGE1), adenosine, l-arginine, phyticacid, bivalirudin, and cilostazol, was analyzed using the orthogonal experimental design. The values of the expression rates of p-selectin (CD62p) and platelet membrane glyeoprotein (PAC-1), as well as of platelet and mean platelet volume (MPV), were selected as indices of platelet activation. The values of CD62p and Pac-1 induced by thrombin w...

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Retraction of: Cilostazol inhibits cytokine-induced nuclear factor-{kappa}B activation via AMP-activated protein kinase activation in vascular endothelial cells

Cardiovascular Research — Wed, 14 Sep 2011 04:00:00 +0100

(Source: Cardiovascular Research)

Cilostazol inhibits matrix invasion and modulates the gene expressions of MMP-9 and TIMP-1 in PMA-differentiated THP-1 cells.

European Journal of Pharmacology — Mon, 12 Sep 2011 04:00:00 +0100

In conclusion, the present study provides an additional mechanism underlying the anti-atherosclerotic effect of cilostazol by inhibiting the monocyte invasion and modulating the gene expressions of MMP-9 and TIMP-1 in monocytes upon differentiating to macrophages. PMID: 21925496 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)

Use of Prasugrel in a Patient with Clopidogrel Hypersensitivity (October).

The Annals of Pharmacotherapy — Tue, 06 Sep 2011 04:00:00 +0100

CONCLUSIONS:Prasugrel may be considered a therapeutic alternative in some patients allergic or intolerant to clopidogrel, but additional data are warranted to make a strong conclusion. PMID: 21896923 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)

Impact of cilostazol after endovascular treatment for infrainguinal disease in patients with critical limb ischemia

Journal of Vascular Surgery — Mon, 29 Aug 2011 04:00:00 +0100

Conclusions: Cilostazol may improve AFS and limb salvage rate after EVT for infrainguinal disease in patients with CLI. (Source: Journal of Vascular Surgery)

Learning to Walk Before We Run: The Mechanics of Medical Intervention for Peripheral Arterial Disease⁎

Journal of the American College of Cardiology — Sat, 27 Aug 2011 13:30:06 +0100

Clinicians are often faced with 2 important issues when treating patients with peripheral arterial disease (PAD) and coronary artery disease (CAD): 1) reduction of cardiovascular risk and 2) improvement of symptoms. Although multiple therapies (antiplatelet agents, statins, antihypertensive agents) have been proven to reduce cardiovascular risk in both CAD and PAD patients, unlike CAD, very few therapeutic agents have been shown to improve leg symptoms in PAD patients. Statins are currently listed as a Class IB recommendation in the PAD guidelines with specific recommendations about low-density lipoprotein (LDL) goals, but no recommendation about their use for symptom management (). The current guideline-based approach for PAD patients with intermittent claudication is to recommend aerobic...

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Inhibitory Interaction Between Calcium Channel Blocker and Clopidogrel.

Circulation Journal — Fri, 19 Aug 2011 23:00:00 +0100

Conclusions: Concomitant use of CCB may weaken the anti-platelet effect of clopidogrel and increase subsequent thrombotic events in Asian subjects. This hazardous CCB-clopidogrel interaction may be overcome by addition of cilostazol. PMID: 21857144 [PubMed - as supplied by publisher] (Source: Circulation Journal)

Benefit, rather than safety, of cilostazol for long-term mortality in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized trials

International Journal of Cardiology — Thu, 18 Aug 2011 04:00:00 +0100

On the basis of an extensive efficacy database substantiating treatment benefit on improvements in peak exercise performance and quality of life in patients with claudication , cilostazol was approved by the United States FDA (Food and Drug Administration) to treat the symptom of claudication. Cilostazol, however, is a member of the phosphodiesterase-III drug class, and other drugs from this class have been associated with excess mortality when used in patients with heart failure. The long-term administration of milrinone for the treatment of heart failure was associated with a statistically significant 28% increase in all-cause mortality . The CASTLE (Cilostazol: A Study in Long-term Effects) study demonstrated no long-term (36-month) safety signal for cilostazol on all-cause or cardiovas...

Cilostazol Stimulates Revascularisation in Response to Ischaemia via an eNOS-Dependent Mechanism

European Journal of Vascular and Endovascular Surgery — Thu, 18 Aug 2011 04:00:00 +0100

Abstract: Objectives: Cilostazol is known to be a selective inhibitor of phosphodiesterase 3 and is generally used to treat intermittent claudication caused by peripheral arterial disease. However, there is little information concerning the effect of cilostazol on angiogenesis. Here, we investigated whether cilostazol modulates the angiogenic process in vivo employing a hindlimb model of ischaemia-induced angiogenesis.Design: This was an experimental study.Materials and methods: Wild-type (WT) mice were randomly divided into two groups and were treated with or without cilostazol. One week later, the mice were subjected to unilateral hindlimb ischaemia. Angiogenesis was determined by laser Doppler analysis and capillary density stained with CD31. The expression of endothelial nitric oxide ...

Cilostazol Stimulates Revascularisation in Response to Ischaemia via an eNOS-Dependent Mechanism.

PubMed: Eur J Vasc Endovasc ... — Mon, 15 Aug 2011 23:00:00 +0100

CONCLUSIONS: Our observations indicate that cilostazol can promote neo-vascularisation in response to tissue ischaemia via an eNOS-dependent mechanism. Cilostazol could be useful for treatment of ischaemic limb diseases. PMID: 21852163 [PubMed - as supplied by publisher] (Source: PubMed: Eur J Vasc Endovasc ...)

A randomized study assessing the effects of pretreatment with cilostazol on periprocedural myonecrosis after percutaneous coronary intervention.

Yonsei Medical Journal — Mon, 15 Aug 2011 14:55:10 +0100

Conclusion: This trial demonstrated that adjunctive cilostazol pretreatment might not significantly reduce PPMN after elective PCI in patients with stable angina. PMID: 21786434 [PubMed - in process] (Source: Yonsei Medical Journal)

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Antiplatelet therapies comparable in intracranial stenosis

Modern Medicine — Sun, 14 Aug 2011 23:00:00 +0100

NEW YORK (Reuters Health) - Aspirin in combination with cilostazol or clopidogrel appears to have a similar inhibitory effect on progression of symptomatic intracranial atherosclerotic stenosis (ICAS), Korean researchers report. However, cilostazol may have advantages. (Source: Modern Medicine)

Clopidogrel-Induced Neutropenia after Coronary Stenting: Is Cilostazol a Good Alternative?

Diagnostic and Therapeutic Endoscopy — Thu, 11 Aug 2011 14:15:38 +0100

We report a case of clopidogrel-induced bone marrow toxicity manifesting with severe neutropenia in a patient treated with multiple coronary stents and provide suggestions for an alternative treatment. (Source: Diagnostic and Therapeutic Endoscopy)

Clopidogrel Resistance: Identifying and Overcoming a Barrier to Effective Antiplatelet Treatment

Cardiovascular Therapeutics — Sat, 30 Jul 2011 23:00:00 +0100

SUMMARYClopidogrel is an inhibitor of the ADP receptor P2Y12 and platelet aggregation. It is widely used for the management of atherothrombotic disease in patients who have experienced severe vascular events such as stroke or myocardial infarction or with peripheral artery disease. However, some patients show “resistance” to clopidogrel, and show impaired inhibition of platelet aggregation. In this review, I discuss the clinical evidence of the extent of the problem, potential implications for future cardiovascular events and clinical tests to assess platelet aggregation. I also discuss the mechanisms that appear responsible for clopidogrel resistance. Clopidogrel is administered as a prodrug and the active metabolite is generated by the cytochrome P450 system. Therefore, inadequate re...

Restenosis after stent implantation for superficial femoral artery disease in patients treated with cilostazol

Catheterization and Cardiovascular Interventions — Thu, 28 Jul 2011 23:00:00 +0100

Conclusions:Cilostazol reduced restenosis after SFA stenting with self‐expandable nitinol stent and it seems to be more effective in high‐risk patients for restenosis. © 2011 Wiley‐Liss, Inc. (Source: Catheterization and Cardiovascular Interventions)

Timing of the restenosis following nitinol stenting in the superficial femoral artery and the factors associated with early and late restenoses

Catheterization and Cardiovascular Interventions — Thu, 28 Jul 2011 23:00:00 +0100

Conclusions: Restenosis predominantly occurred within a year following nitinol stenting in the SFA, and the factors associated with the early restenosis were different from those with the late restenosis. © 2011 Wiley‐Liss, Inc. (Source: Catheterization and Cardiovascular Interventions)

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Effect of the antiplatelet agent cilostazol on endovascular inflammatory biochemical parameters and the clinical symptoms of peripheral artery disease and restless legs syndrome in hemodialysis patients

Clinical and Experimental Nephrology — Tue, 19 Jul 2011 23:37:42 +0100

Conclusion The treatment of HD patients with cilostazol improved some of the lipid-related and endovascular inflammatory biochemical parameters associated with PAD, and relieved the clinical symptoms and physical status of PAD in some cases. Content Type Journal ArticlePages 1-7DOI 10.1007/s10157-011-0485-2Authors Shunji Shiohira, Department of Medicine IV, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, JapanTakumi Yoshida, Department of Medicine IV, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, JapanHidekazu Sugiura, Department of Medicine IV, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, JapanSatsuki Yoshida, Department of Medicine IV, Tokyo Women’s Medical University, ...

Investigation of nanosized crystalline form to improve the oral bioavailability of poorly water soluble cilostazol.

J Pharm Pharm Sci — Tue, 12 Jul 2011 15:30:03 +0100

Conclusion: The anti-solvent-high-pressure homogenization technique was employed successfully to produce cilostazol nanosuspensions. The bioavailability of CLT tablets prepared using spray dried nanosized crystalline powder after oral administration to dogs was markedly increased compared with that produced by nanosized tablets and commercial tablets, because of its greater dissolution rate owing to its transition of the crystalline state to form C and form B, reduced particle size and porous structure with increased surface area. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID: 21733409 [PubMed - in process] (Source: J Pharm Pharm Sci)

Sex differences in pharmacokinetics of cilostazol in rats.

Xenobiotica — Thu, 30 Jun 2011 23:00:00 +0100

Authors: Kamada N, Yamada K, Odomi M, Mukai T, Nishibayashi T, Ogawara KI, Kimura T, Higaki K The pharmacokinetics of cilostazol was investigated after oral and intravenous administration in both male and female rats. After oral administration, area under serum concentration-time curve (AUC) was about 35-fold higher in female rats than in male rats, and absolute bioavailability was about 5.8-fold higher in female rats than in male rats. Total body clearance (CL(total)) for female rats was around one-sixth of that for male rats. In vivo hepatic clearance (CL(h)) calculated based on isolated liver perfusion studies was even higher than or around 90% of the in vivo CL(total) of cilostazol for female and male rats, respectively, indicating that cilostazol is mainly eliminated by the liver ...

We Need Further Studies for the Development of “Optimized Antiplatelet Therapy” Based on Ethnicity

Journal of the American College of Cardiology — Wed, 29 Jun 2011 15:52:38 +0100

We read with interest the CILON-T (Influence of Cilostazol-based Triple Antiplatelet Therapy on Ischemic Complication After Drug-Eluting Stent Implantation) trial on the efficacy of cilostazol on ischemic complications after drug-eluting stent (DES) implantation (), which suggested the potential link between platelet reactivity and ischemic events in Asians. (Source: Journal of the American College of Cardiology)

Reply

Journal of the American College of Cardiology — Wed, 29 Jun 2011 15:52:38 +0100

We cordially appreciate the interest of Dr. Jeong and colleagues in our paper () and welcome their comments. The CILON-T (Influence of Cilostazol-based Triple Antiplatelet Therapy on Ischemic Complication After Drug-Eluting Stent Implantation) trial was designed to compare the efficacy and safety of dual and triple antiplatelet therapy in patients undergoing percutaneous coronary intervention in the real-world setting (). It showed that the individual response to antiplatelet therapy rather than the choice of specific regimen is important to predict future adverse events, and it suggested the cut-off P2Y12 reaction unit (PRU) values in Asians, which has not been well reported. (Source: Journal of the American College of Cardiology)

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Are threshold levels of signal transduction required for the protective effect of cilostazol against cardiac ischaemia reperfusion injury?

Clinical and Experimental Pharmacology and Physiology — Mon, 27 Jun 2011 23:00:00 +0100

Authors: Reis F PMID: 21711382 [PubMed - as supplied by publisher] (Source: Clinical and Experimental Pharmacology and Physiology)

Dysthymia and Apathy: Diagnosis and Treatment

Clinical and Developmental Immunology — Mon, 27 Jun 2011 15:55:56 +0100

Dysthymia is a depressive mood disorder characterized by chronic and persistent but mild depression. It is often difficult to be distinguished from major depression, specifically in its partially remitted state because “loss of interest” or “apathy” tends to prevail both in dysthymia, and remitted depression. Apathy may also occur in various psychiatric and neurological disorders, including schizophrenia, stroke, Parkinson's disease, progressive supranuclear palsy, Huntington's disease, and dementias such as Alzheimer's disease, vascular dementia, and frontotemporal dementia. It is symptomatologically important that apathy is related to, but different from, major depression from the viewpoint of its causes and treatment. Antidepressants, especially noradrenergic...

NICE Bites - June 2011: Multiple TA; Peripheral arterial disease & Common mental health disorders

NeLM - Health In Focus — Tue, 21 Jun 2011 23:00:00 +0100

Source: North West Medicines Information Centre Area: Health In Focus NICE Bites is a monthly bulletin which summarises key prescribing points from NICE guidance. This edition includes two topics; Cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease and Common mental health disorders. (Source: NeLM - Health In Focus)

Beneficial effect of anti-platelet therapies on atherosclerotic lesion formation assessed by phase-contrast X-ray CT imaging

The International Journal of Cardiovascular Imaging — Tue, 21 Jun 2011 18:00:05 +0100

In this study, we investigated the effect of the anti-platelet therapies, widely used for secondly prevention of cardiovascular events, on plaque stability and examined whether this novel technique could detect the changes of plaque components under the therapy. Apolipoprotein E-deficient mice were fed on high-cholesterol diet alone and either with 0.1% cilostazol or clopidogrel for 10 weeks. We assessed atherosclerotic lesion volumes and components at brachiocephalic artery by the phase-contrast X-ray CT imaging and histochemistry. The phase-contrast X-ray CT imaging could reveal that cilostazol and clopidogrel significantly decreased atherosclerotic lesion volumes at brachiocephalic artery (31.2% reduction in cilostazol group and 37.4% reduction in clopidogrel group), compared...

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Cilostazol Promotes Vascular Smooth Muscles Cell Differentiation Through the cAMP Response Element-Binding Protein-Dependent Pathway.

Arteriosclerosis, Thrombosis and Vascular Biology — Wed, 15 Jun 2011 23:00:00 +0100

CONCLUSIONS: Cilostazol promotes VSMC differentiation through the cAMP/PKA/CREB signaling cascade. PMID: 21680899 [PubMed - as supplied by publisher] (Source: Arteriosclerosis, Thrombosis and Vascular Biology)

Cilostazol protects the heart against ischaemia reperfusion injury in a rabbit model of myocardial infarction: Focus on adenosine, nitric oxide and mitochondrial KATP channels.

Clinical and Experimental Pharmacology and Physiology — Tue, 14 Jun 2011 23:00:00 +0100

This study examined whether cilostazol reduces the myocardial infarct size and to investigated its mechanism in a rabbit model of myocardial infarction. 2) Japanese white rabbits underwent 30 min of coronary occlusion, followed by 48 hours of reperfusion. Cilostazol (1 and 5 mg/kg) or vehicle was intravenously administered 5 min before ischaemia. 8-p-Sulfophenyl theophylline (8SPT, an adenosine receptor blocker, 7.5 mg/kg), Nω-nitro-L-arginine methylester (L-NAME, an NOS inhibitor, 10 mg/kg), or 5-hydroxydecanoic acid sodium salt (5-HD, a mitochondrial KATP channel blocker, 5 mg/kg) was intravenously administered 5 min before cilostazol injection. Infarct size was determined as a percentage of the risk area. 3) The myocardial interstitial levels of adenosine and nitrogen oxide (NOx) d...

Cilostazol Improves Outcome after Subarachnoid Hemorrhage: A Preliminary Report

Karger Publishers — Fri, 10 Jun 2011 14:16:04 +0100

Cerebrovasc Dis 2011;32:89–93 (DOI:10.1159/000327040) (Source: Karger Publishers)

Effect of type II endoleaks and antiplatelet therapy on abdominal aortic aneurysm shrinkage after endovascular repair

Journal of Vascular Surgery — Fri, 10 Jun 2011 04:00:00 +0100

Conclusion: Patients with a persistent type II endoleak and patients undergoing multiagent antiplatelet therapy are at an increased risk of a lack of aneurysm shrinkage 6 months after EVAR. (Source: Journal of Vascular Surgery)

Anti‐platelet therapy: Phosphodiesterase inhibitors

British Journal of Clinical Pharmacology — Tue, 07 Jun 2011 23:00:00 +0100

SUMMARYInhibition of platelet aggregation can be achieved by either the blockade of membrane receptors or by interaction with intracellular signalling pathways. Cyclic adenosine 3’‐5’‐monophosphate (cAMP) and cyclic guanosine 3’‐5‐monophosphate (cGMP) are two critical intracellular second messengers provided with strong inhibitory activity on fundamental platelet function. Phosphodiesterases (PDEs), by catalyzing the hydrolysis of cAMP and cGMP, limit the intracellular levels of cyclic nucleotides thus regulating platelet function. The inhibition of PDEs may therefore exert a strong platelet inhibitory effect. Platelets possess three PDE isoforms: PDE2, PDE3 and PDE5, with different selectivity for cAMP and cGMP. Several non selective or isoenzyme selective PDE inhibitors hav...

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Medical Management of the Patient with Intermittent Claudication

Cardiology Clinics — Sun, 05 Jun 2011 23:00:00 +0100

Intermittent claudication (IC) due to peripheral arterial disease (PAD) causes substantial impairment in quality of life, and is strongly associated with increased cardiovascular morbidity and mortality. The overall medical approach to management focuses on reducing cardiovascular events, preventing progression of underlying PAD (eg, limb loss), and improving symptoms. Aggressive secondary prevention strategies (eg, statins and smoking cessation) are of critical importance. Cilostazol treatment should be considered for those with persistent IC symptoms despite exercise and risk factor control. Management of IC requires a comprehensive approach toward symptomatic relief of pain with strategies that prolong life and prevent limb loss. (Source: Cardiology Clinics)

Toxic epidermal necrolysis with fatal ending due to the concurrent use of carbamazepine, cilostazol and omeprazol: a case report.

Farmacia Hospitalaria — Thu, 02 Jun 2011 23:00:00 +0100

Authors: Concepción Martín I, Fernández de Palencia Espinosa MA, Garrido Corro B, De La Rubia Nieto A PMID: 21641845 [PubMed - as supplied by publisher] (Source: Farmacia Hospitalaria)

A meta-analysis of randomized trials of triple versus dual antiplatelet therapy after stent-based percutaneous coronary intervention

International Journal of Cardiology — Wed, 01 Jun 2011 23:00:00 +0100

Cilostazol in addition to dual antiplatelet therapy (aspirin and clopidogrel) may be associated with a reduction in target lesion revascularization (TLR) and no difference in subacute stent thrombosis in patients undergoing stent-based percutaneous coronary intervention (PCI) . However, the appropriate role of triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol) for prevention of major adverse cardiac events in stent-based PCI population remains unclear, because previous meta-analyses included a few randomized controlled trials. We performed a meta-analysis of randomized trials of triple versus dual antiplatelet therapy for prevention of each component of major adverse cardiac events in stent-based PCI. (Source: International Journal of Cardiology)

Cilostazol, a Type III Phosphodiesterase Inhibitor, Reduces Ischemia/Reperfusion-Induced Spinal Cord Injury.

The Heart Surgery Forum — Tue, 31 May 2011 23:00:00 +0100

Conclusion: Administration of cilostazol before spinal cord ischemia reduced neurologic injury and produced clinical improvement by attenuating oxidative stress in this rat spinal cord I/R model. PMID: 21676683 [PubMed - in process] (Source: The Heart Surgery Forum)

Detection of Clopidogrel Hyporesponsiveness Using a Point-of-Care Assay and the Impact of Additional Cilostazol Administration after Coronary Stent Implantation in Diabetic Patients.

The Korean Journal of Internal Medicine — Tue, 31 May 2011 23:00:00 +0100

Authors: Yang TH, Kim DI, Kim DK, Jang JS, Kim U, Seol SH, Kim DK, Hong GR, Park JS, Shin DG, Kim YJ, Cho YK, Nam CW, Hur SH, Kim KB, Kim DS Impaired responsiveness to clopidogrel is common in patients with type 2 diabetes mellitus (DM). The aim of this study was to evaluate the clinical application of a point-of-care assay to detect impaired responsiveness to clopidogrel after coronary stent implantation in patients with type 2 DM. PMID: 21716590 [PubMed - in process] (Source: The Korean Journal of Internal Medicine)

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Impact of adjunctive cilostazol therapy on platelet function profiles in patients with and without diabetes mellitus on aspirin and clopidogrel therapy.

Thrombosis and Haemostasis — Wed, 25 May 2011 23:00:00 +0100

Authors: Angiolillo DJ, Capranzano P, Ferreiro JL, Ueno M, Capodanno D, Dharmashankar K, Darlington A, Sumner S, Desai B, Charlton RK, Box LC, Zenni M, Guzman LA, Bass TA Cilostazol is a platelet inhibitor which when added to aspirin and clopidogrel has shown to reduce the risk of recurrent ischaemic events without an increase in bleeding. These clinical benefits have shown to be more pronounced in patients with diabetes mellitus (DM). However, it remains unknown whether cilostazol exerts different pharmacodynamic effects in patients with and without DM. This was a randomised, double-blind, placebo-controlled, cross-over pharmacodynamic study comparing platelet function in patients with and without DM on aspirin and clopidogrel therapy. Patients (n=111) were randomly assigned to either...

NICE issues guidance on cilostazol, naftidrofyryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication

NeLM - Guidelines — Tue, 24 May 2011 23:00:00 +0100

Source: NICE Area: Evidence > Guidelines The National Institute for Health and Clinical Excellence (NICE) has issued guidance on the use of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in patients with peripheral arterial disease. The following recommendations have been made (taken directly from source): . Naftidrofuryl oxalate is recommended as an option for the treatment of intermittent claudication in people with peripheral arterial disease for whom vasodilator therapy is considered appropriate after taking into account other treatment options. Treatment with naftidrofuryl oxalate should be started with the least costly licensed preparation. . Cilostazol, pentoxifylline ...

Application of Adaptive Design and Decision Making to a Phase II Trial of a Phosphodiesterase Inhibitor for the Treatment of Intermittent Claudication

Trials — Tue, 24 May 2011 23:00:00 +0100

Conclusions: In this phase II, dose-finding trial of K-134 in the treatment of stable intermittent claudication, no concerning safety signals were seen at interim analysis, allowing the discontinuation of the lowest-dose-containing arm and the retention of the two highest-dose-containing arms. The adaptive design facilitated safe and efficient evaluation of K-134 in this high-risk cardiovascular population.ClinicalTrials.gov Registration: NCT00783081 (Source: Trials)

Pharmacodynamic interaction study of Allium sativum (garlic) with cilostazol in patients with type II diabetes mellitus

Indian Journal of Pharmacology — Mon, 23 May 2011 23:00:00 +0100

Conclusions: Coadministration of aged garlic extract and cilostazol did not enhance the antiplatelet activity compared with individual drugs. Large randomized trials are needed to further evaluate the possible interaction of garlic in higher doses and in combination with other antiplatelet activity drugs. (Source: Indian Journal of Pharmacology)

Standard versus high loading doses of clopidogrel in Asian patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: Insights from the Korea Acute Myocardial Infarction Registry

American Heart Journal — Sun, 22 May 2011 23:00:00 +0100

We read with interest the work by Choi et al, which reported that, from the Korea Acute Myocardial Infarction Registry (KAMIR) results, in Asian patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), a 600-mg loading dose of clopidogrel could not afford additional benefit when compared with a 300-mg loading dose of clopidogrel. However, the previous KAMIR results have demonstrated that cilostazol-based triple therapy would reduce the major adverse cardiac events after primary PCI. Whether the loading dose of clopidogrel in the condition of cilostazol therapy affecting the major adverse cardiac event rates is still unknown and should be further investigated. In addition, the effectiveness of high loading dose of clopidog...

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European CHMP begins benefit-risk assessment of cilostazol-containing medicines,

NeLM - News — Thu, 19 May 2011 23:00:00 +0100

Source: European Medicines Agency (EMA) Area: News The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has started a benefit-risk assessment of cilostazol-containing medicines, currently used to improve the maximal walking distance and maximal pain-free walking distances in patients with intermittent claudication. This review was triggered by Spain following the review of all safety reports during the first 18 months of marketing of these medicines. The safety review showed an increased risk of cardiovascular and haemorrhagic reactions. This increased risk has to be assessed in the light of a modest clinical efficacy mainly shown in a population younger than the population receiving these medicines in daily practice. The Committee will now revi...

Cilostazol: A Potential Therapeutic Option to Prevent In-Stent Restenosis

Journal of the American College of Cardiology — Thu, 12 May 2011 15:43:20 +0100

It was of great interest and utility to read the paper by Dangas et al. () pertaining to in-stent restenosis (ISR) in drug-eluting stents (DES). The authors reviewed systematically the pathophysiological, mechanical, and technical mechanisms and treatment options of ISR in DES. The proposed treatment algorithm is an important clinical tool for a challenging problem without a proven treatment regimen. We would like to present another possible treatment option available for ISR. We believe that the platelet phosphodiesterase III (PDE III) inhibitor cilostazol may potentially have a beneficial role in the treatment of ISR in DES. (Source: Journal of the American College of Cardiology)

Cilostazol: a drug particularly effective for Asians?

International Journal of Stroke — Wed, 11 May 2011 19:10:43 +0100

Cilostazol is an antiplatelet drug often used in Asia; however, it is rarely used in the western hemisphere, particularly for stroke patients. Further studies of cilostazol in other ethnicities are required to prove or disprove whether this drug is also beneficial in non‐Asian populations. (Source: International Journal of Stroke)

Cilostazol in patients with ischemic stroke

Expert Opinion: Expert Opinion on Pharmacotherapy: Table of Contents — Fri, 06 May 2011 13:25:46 +0100

Expert Opinion on Pharmacotherapy, Volume 0, Issue 0, Page 1305-1315, Early Online. (Source: Expert Opinion: Expert Opinion on Pharmacotherapy: Table of Contents)

Optimizing of thienopyridine therapy by multiple electrode platelet aggregometry in clopidogrel low responders undergoing PCI

Clinical Research in Cardiology — Fri, 29 Apr 2011 15:47:19 +0100

Conclusion Clopidogrel low response is present in 1/10 patients and more frequent in ACS-PCI. MEA-guided optimizing of thienopyridine therapy is feasible and results in a very low specific MACCE rate. Low response to all thienopyridines is rare. Content Type Journal ArticlePages 1-8DOI 10.1007/s00392-011-0321-4Authors Tobias Behr, Medizinische Klinik, Klinikum Augsburg, Stenglinstr. 2, 86156 Augsburg, GermanyBernhard Kuch, Medizinische Klinik, Klinikum Augsburg, Stenglinstr. 2, 86156 Augsburg, GermanyWerner Behr, Institut für Laboratoriumsmedizin, Klinikum Augsburg, Augsburg, GermanyWolfgang von Scheidt, Medizinische Klinik, Klinikum Augsburg, Stenglinstr. 2, 86156 Augsburg, Germany Journal Clinical Research in CardiologyOnline ISSN 1861-0692Print ISSN 1861-0...

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Cilostazol minimizes venous ischemic injury in diabetic and normal rats

Journal of Cerebral Blood Flow — Tue, 19 Apr 2011 23:00:00 +0100

Authors: Daisuke Wajima, Mitsutoshi Nakamura, Kaoru Horiuchi, Yasuhiro Takeshima, Fumihiko Nishimura & Hiroyuki Nakase (Source: Journal of Cerebral Blood Flow)

Platelet Inhibition by Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel in Patients With Acute Myocardial Infarction According to Cytochrome P450 2C19 Genotype

Journal of the American College of Cardiology: Cardiovascular Interventions — Sun, 17 Apr 2011 23:00:00 +0100

Conclusions Compared with high-MD clopidogrel, adjunctive cilostazol significantly enhances platelet inhibition and reduces the rate of HPR, especially in AMI patients with CYP2C19 loss-of-function variants. (Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel in Acute Myocardial Infarction (AMI) Patients According to CYP2C19 Polymorphism [ACCELAMI2C19]; NCT00915733) (Source: Journal of the American College of Cardiology: Cardiovascular Interventions)

Effect of dibutyryl cyclic adenosine monophosphate on the gene expression of plasminogen activator inhibitor-1 and tissue factor in adipocytes

Thrombosis Research — Fri, 15 Apr 2011 04:00:00 +0100

Abstract: Introduction: Hypertrophic adipocytes in obese states express the elevated levels of plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF). An increase in the intracellular concentration of cyclic adenosine monophosphate (cAMP) promotes triglyceride hydrolysis and may improve dysregulation of adipocyte metabolism. Here, we investigate the effect of dibutyryl-cAMP (a phosphodiesterase-resistant analog of cAMP) on the gene expression of PAI-1 and TF in adipocytes.Materials and methods: Differentiated 3T3-L1 adipocytes were treated with dibutyryl-cAMP and agents that would be expected to elevate intracellular cAMP, including cilostazol (a phosphodiesterase inhibitor with anti-platelet and vasodilatory properties), isoproterenol (a beta adrenergic agonist) and forskolin (a...

NICE issues FAD on cilostazol, naftidrofyryl oxalate, pentoxifylline and inositol nicotinate for peripheral arterial disease

NeLM - News — Wed, 13 Apr 2011 23:00:00 +0100

Source: NICE Area: News NICE has issued a Final Appraisal Determination (FAD) on cilostazol, naftidrofyryl oxalate, pentoxifylline and inositol nicotinate for peripheral arterial disease, which contains the following draft recommendations: . Naftidrofuryl oxalate is recommended as an option for the treatment of intermittent claudication in people with peripheral arterial disease for whom vasodilator therapy is considered appropriate after taking into account other treatment options. Treatment with naftidrofuryl oxalate should be started with the least costly licensed preparation. . Cilostazol, pentoxifylline and inositol nicotinate are not recommended for the treatment of intermittent claudication in people with peripheral arterial disease. The a...

Determinants of Lower Extremity Amputation or Revascularization Procedure in Patients With Peripheral Artery Diseases: A Population-Based Investigation

Angiology — Tue, 05 Apr 2011 23:00:00 +0100

In conclusion, PAD patients having DM and using cilostazol had less LEA or PRP, whereas those having HTN and CAD had more LEA or PRP. (Source: Angiology)

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Impact of Cilostazol on Left Ventricular Geometry and Function: Assessment by Tissue Doppler Imaging and Two‐Dimensional Speckle‐Tracking Echocardiography

Echocardiography — Thu, 31 Mar 2011 23:00:00 +0100

Conclusion: Positive inotropic and chronotropic effects of cilostazol were found based on assessment by TDI and 2D‐STE. We suggest that periodic echocardiographic assessment should be performed before and after oral administration of cilostazol. (Echocardiography 2011;28:431‐437) (Source: Echocardiography)

Protective Effects of Cilostazol against Transient Focal Cerebral Ischemia and Hemorrhagic Transformation.

Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan — Thu, 31 Mar 2011 23:00:00 +0100

This article reviews the protective effects of cilostazol against transient focal cerebral ischemia and hemorrhagic transformation and its mechanism of action. PMID: 21467790 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)

Blockade of Phosphodiesterase-III Protects against Oxygen-Glucose Deprivation in Endothelial Cells by Upregulation of VE-Cadherin.

Current Neurovascular Research — Sun, 27 Mar 2011 23:00:00 +0100

Authors: Ishiguro M, Suzuki Y, Mishiro K, Kakino M, Tsuruma K, Shimazawa M, Yoshimura S, Iwama T, Har H We recently reported that a phosphodiesterase-III inhibitor, cilostazol, prevented the hemorrhagic transformation induced by focal cerebral ischemia in mice treated with tissue plasminogen activator (tPA) and that it reversed tPA-induced cell damage by protecting the neurovascular unit, particularly endothelial cells. However, the mechanisms of cilostazol action are still not clearly defined. The adheren junction (AJ) protein, VE-cadherin, is a known mediator of endothelial barrier sealing and maintenance. Therefore, we tested whether cilostazol might promote expression of adhesion molecules in endothelial cells, thereby preventing deterioration of endothelial barrier functions. Huma...

Evaluation of anti-platelet and anti-thrombotic effects of cilostazol with PFA-100® and Multiplate® whole blood aggregometer in vitro, ex vivo and FeCl3-induced thrombosis models in vivo

Thrombosis Research — Mon, 21 Mar 2011 00:00:00 +0100

Abstract: We evaluate the anti-platelet and anti-thrombotic effects of cilostazol using Multiplate® and PFA-100® in vitro and ex vivo with freshly isolated rat whole blood and in vivo venous and arterial thrombosis models in the same species, in an effort to assess the sensitivity of the whole blood aggregometer assays without potential issues of species differences. In vitro assay of anti-platelet effects of cilostazol against collagen-induced aggregation using Multiplate® produced a graded dose-dependent inhibition curve with IC50 value of 75.4±2.4μM while it showed a highly sensitive and all-or-none type inhibition response from 25μM in PFA-100®. Interestingly, cilostazol manifested anti-thrombotic effects in vivo at much lower plasma concentrations than the effective concentrati...

In vitro dissolution/permeation system to predict the oral absorption of poorly water-soluble drugs: effect of food and dose strength on it.

Biological and Pharmaceutical Bulletin — Sat, 19 Mar 2011 04:15:03 +0100

Authors: Kataoka M, Itsubata S, Masaoka Y, Sakuma S, Yamashita S The aim of the present work was to confirm the usefulness of the dissolution/permeation system (D/P system) in the estimation of human oral absorption of poorly water-soluble drugs. The D/P system, which can simultaneously evaluate drug absorption processes, dissolution and permeation, can predict the oral absorption of poorly water-soluble drugs in fasted and fed humans, with a correlation between in vivo oral absorption (% of absorbed) and in vitro permeated amount (% of dose/2 h) in the D/P system. The oral absorption (fraction of absorbed dose, %) of poorly water-soluble drugs in the fasted and fed states was predicted using the D/P system. The effect of food on the oral absorption of various drugs estimated by the D/...

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Cilostazol attenuates on-treatment platelet reactivity in patients with CYP2C19 loss of function alleles receiving dual antiplatelet therapy: a genetic substudy of the CILON-T randomised controlled trial

Heart — Fri, 18 Mar 2011 00:00:00 +0100

Conclusion TAT significantly reduced OPR compared with DAT in carriers of the CYP2C19 LOF allele, but not in non-carriers. These data suggest that the addition of cilostazol to DAT may be a good strategy to attenuate CYP2C19 LOF-related high OPR. (Source: Heart)

A Randomized, Double-Blind, Multicenter Comparison Study of Triple Antiplatelet Therapy With Dual Antiplatelet Therapy to Reduce Restenosis After Drug-Eluting Stent Implantation in Long Coronary Lesions: Results From the DECLARE-LONG II (Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients with Long Coronary Lesions) Trial

Journal of the American College of Cardiology — Tue, 15 Mar 2011 00:00:00 +0100

Conclusions: Patients receiving triple antiplatelet therapy after long zotarolimus-eluting stent implantation had decreased extent of late luminal loss, percent intimal hyperplasia volume, and angiographic restenosis, resulting in a reduced risk of 12-month target lesion revascularization compared with patients receiving dual antiplatelet therapy. (Triple Versus Dual Antiplatelet Therapy after ABT578-Eluting Stent; NCT00589927) (Source: Journal of the American College of Cardiology)

cAMP regulates ADP-induced HSP27 phosphorylation in human platelets.

International Journal of Molecular Medicine — Thu, 03 Mar 2011 00:00:00 +0100

Authors: Enomoto Y, Adachi S, Doi T, Natsume H, Kato K, Matsushima-Nishiwaki R, Akamatsu S, Tokuda H, Yoshimura S, Otsuka T, Ogura S, Kozawa O, Iwama T Elevation of cAMP in platelets is recognized to play a suppressive role in platelet functions. We have previously shown that adenosine diphosphate (ADP)-induced phosphorylation of heat shock protein 27 (HSP27) via p38 mitogen-activated protein (MAP) kinase is correlated with platelet-derived growth factor (PDGF)-AB secretion and soluble CD40 ligand (sCD40L) release. In the present study, we investigated the relationship between cAMP and HSP27 phosphorylation in platelet function. 8-Bromoadenosine-3',5'-cyclic monophosphate (8-bromo-cAMP), a plasma membrane-permeable cAMP analogue, or cilostazol, an inhibitor of cAMP phosphodiesterase, ...

Cilostazol enhances integrin‐dependent homing of progenitor cells by activation of camp‐dependent protein kinase in synergy with Epac1

Journal of Neuroscience Research — Fri, 18 Feb 2011 02:56:32 +0100

In conclusion, cilostazol stimulated integrin expression and enhanced migration and adhesion of progenitor cells through cooperative activation of PKA and Epac signals; such activity may improve the efficacy of cell therapy for ischemic disease. © 2011 Wiley‐Liss, Inc. (Source: Journal of Neuroscience Research)

Aspirin, P2Y12 blockers, cilostazol, PAR-1 blockers and emerging antiplatelet therapies: can biomarkers guide clinical development and practice?

Future Medicine: Biomarkers in Medicine — Tue, 15 Feb 2011 04:00:13 +0100

Biomarkers in Medicine , February 2011, Vol. 5, No. 1, Pages 1-3. (Source: Future Medicine: Biomarkers in Medicine)

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Comparison of 600 Versus 300-mg Clopidogrel Loading Dose in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Coronary Angioplasty

The American Journal of Cardiology — Sat, 12 Feb 2011 15:47:19 +0100

The rationale for the use of a double dose of clopidogrel in the study of Mangiacapra et al for those with ST-segment elevation myocardial infarction (STEMI) who underwent primary coronary angioplasty was to rapidly suppress platelet activity to avoid subsequent cardiovascular ischemic events. As is known, other adjuvant antiplatelet therapy trials for patients with STEMI who undergo primary angioplasty have revealed similar results, with reductions of cardiovascular end points and events of acute and subacute instant thrombosis. However, additional benefits have been emphasized, especially for those with high risk profiles. For example, in the Korean Acute Myocardial Infarction Registry, Chen et al pointed out that cilostazol-based triple therapy should be used for elderly, female, and di...

Long-Term Results of the S.M.A.R.T. Control(TM) Stent for Superficial Femoral Artery Lesions, J-SMART Registry.

Circulation Journal — Fri, 11 Feb 2011 00:00:00 +0100

Conclusions: The S.M.A.R.T. Control(TM) stent provided good long-term durability in the treatment of SFA lesions, and no cilostazol administration, female gender, younger age and CTO were associated with re-stenosis. PMID: 21325721 [PubMed - as supplied by publisher] (Source: Circulation Journal)

Suppression of Experimental Abdominal Aortic Aneurysm in a Rat Model by the Phosphodiesterase 3 Inhibitor Cilostazol

Journal of Surgical Research — Wed, 09 Feb 2011 00:00:00 +0100

Background: The present experiments sought to determine whether cilostazol, a selective inhibitor of cyclic adenosine monophosphate (cAMP) phosphodiesterase 3 (PDE3), suppressed elastase-induced abdominal aortic aneurysm (AAA) development in a rat model.Methods: Male Sprague-Dawley rats (n = 16/each group) were randomly distributed into three groups: sham-, saline-, and cilostazol-. Rats of saline and cilostazol groups underwent intra-aortic elastase perfusion to induce AAAs, while rats of sham-group were perfused with saline. Rats of cilostazol-group received cilostazol treatment (100 mgkg−1d−1) for the entire experimental period. The areas of the lumen of the aortas at the segment with maximum diameter were measured preperfusion and on d 7, 14 after perfusion. Systolic blood pressu...

Comparison of Dual Drug-Eluting Cilotax Stent and Paclitaxel-Eluting Taxus Liberte Stent in Native Coronary Artery Lesions

The American Journal of Cardiology — Tue, 08 Feb 2011 00:00:00 +0100

In conclusion, the Cilotax stent was safe and effective in decreasing late loss, indicating that this stent represents a promising new type of DES system. (Source: The American Journal of Cardiology)

Cilostazol versus aspirin for secondary prevention of vascular events after stroke of arterial origin.

Cochrane Database of Systematic Reviews — Wed, 02 Feb 2011 16:15:07 +0100

Authors: Kamal AK, Naqvi I, Husain MR, Khealani BA Aspirin is widely used for secondary prevention after stroke. Cilostazol has shown promise as an alternative to aspirin in Asian people with stroke. PMID: 21249700 [PubMed - in process] (Source: Cochrane Database of Systematic Reviews)

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Cilostazol and atherogenic dyslipidemia: a clinically relevant effect?

Expert Opinion: Expert Opinion on Pharmacotherapy: Table of Contents — Wed, 02 Feb 2011 12:17:32 +0100

Expert Opinion on Pharmacotherapy, Volume 0, Issue 0, Page 1-9, Early Online. (Source: Expert Opinion: Expert Opinion on Pharmacotherapy: Table of Contents)

NICE issues preliminary recommendations (ACD) on cilostazol, naftidrofyryl oxalate, pentoxifylline and inositol nicotinate for peripheral arterial disease

NeLM - News — Tue, 01 Feb 2011 00:00:00 +0100

Source: NICE Area: News NICE has been asked by the Department of Health to produce guidance on using cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease (PAD) in the NHS in England and Wales. An Appraisal Consultation Document (ACD) is now available, containing the following preliminary recommendations: . Naftidrofuryl oxalate is recommended as an option for the treatment of intermittent claudication in people with peripheral arterial disease for whom vasodilator therapy is considered clinically appropriate. Treatment with naftidrofuryl oxalate should be started with the least costly licensed preparation. . Cilostazol, pentoxifylline and ino...

Induction of heme oxygenase-1 expression by cilostazol contributes to its anti-inflammatory effects in J774 murine macrophages.

Immunology Letters — Wed, 19 Jan 2011 00:00:00 +0100

Authors: Park SY, Lee SW, Baek SH, Lee SJ, Lee WS, Rhim BY, Hong KW, Kim CD The effects of cilostazol on stimulating heme oxygenase (HO)-1 expression including signal pathways and suppression of inflammatory cytokines and molecules, were studied. Cilostazol stimulation time (1-8hours)- and concentration (1-30μM)-dependently increased the HO-1 mRNA and protein expression associated with increased HO-1 activity, as did cobalt protoporphyrin IX (1-3μM) in J774A.1 macrophages. In addition, cilostazol (1-30μM) concentration-dependently reduced lipopolysaccharide (LPS)-mediated nitrite and TNF-α production, in accordance with the inhibition of LPS-stimulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in the J774 macrophages, as did CoPP (1μM)....

JACC: Triple-antiplatelet therapy is no better than dual therapy

Cardiovascular Business News — Mon, 17 Jan 2011 20:03:20 +0100

Despite a greater reduction of platelet reactivity by the addition of cilostazol to conventional dual-antiplatelet therapy, triple-antiplatelet therapy did not show superiority in reducing the composite of adverse cardiovascular outcomes after drug-eluting stent implantation, according to a study in the Jan. 18 Journal of the American College of Cardiology. (Source: Cardiovascular Business News)

Study design and rational of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

Trials — Wed, 12 Jan 2011 00:00:00 +0100

Discussion: The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier #NCT01031667). (Source: Trials)

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Extrapleural hematoma as a complication following thoracotomy for pulmonary lobectomy

General Thoracic and Cardiovascular Surgery — Tue, 11 Jan 2011 18:08:27 +0100

We report a case of an extrapleural hematoma following pleural lobectomy that resolved completely with nonsurgical treatment. A 63-year-old woman underwent left lower lobectomy for lung cancer through a left posterolateral thoracotomy. She had been prescribed the anticoagulant cilostazol to increase her heart rate for atrioventricular dissociation. Preoperatively, it was stopped, and a temporary pacemaker was placed to counteract bradycardia via the right jugular vein without complication. The chest tube was removed, and cilostazol was resumed on the third postoperative day. On day 7, she suddenly experienced left shoulder pain followed by hypotension, tachycardia, and anemia. Enhanced computed tomography (CT) revealed an extrapleural hematoma rather than a hemothorax. She became sym...

Antiplatelet Drugs: A Review of Their Pharmacology and Management in the Perioperative Period.

Anesthesia and Analgesia — Thu, 06 Jan 2011 00:00:00 +0100

Authors: Hall R, Mazer CD In the normal course of the delivery of care, anesthesiologists encounter many patients who are receiving drugs that affect platelet function as a fundamental part of primary and secondary management of atherosclerotic thrombotic disease. There are several antiplatelet drugs available for use in clinical practice and several under investigation. Aspirin and clopidogrel (alone and in combination) have been the most studied and have the most favorable risk-benefit profiles of drugs currently available. Prasugrel was recently approved for patients with acute coronary syndrome undergoing percutaneous interventions. Other drugs such as dipyridamole and cilostazol have not been as extensively investigated. There are several newer investigational drugs such as cangre...

Cilostazol

Practical Diabetes International — Sat, 01 Jan 2011 00:00:00 +0100

(Source: Practical Diabetes International)

Cilostazol vs. Aspirin for Recurrent-Stroke Prevention

Medscape Today Headlines — Fri, 10 Dec 2010 04:00:00 +0100

Is the phosphodiesterase inhibitor cilostazol as effective as aspirin at preventing recurrent stroke? Journal Watch (Source: Medscape Today Headlines)

What is the optimal duration of triple anti-platelet therapy in patients with acute myocardial infarction undergoing drug-eluting stent implantation?

Journal of Cardiology — Thu, 09 Dec 2010 00:00:00 +0100

CONCLUSIONS: Our data show that the DTAP ≥3 months is associated with better clinical outcomes compared with that of <3 months in patients with AMI undergoing DES implantation without increasing bleeding complications. PMID: 21146365 [PubMed - as supplied by publisher] (Source: Journal of Cardiology)

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Cilostazol reduces the progression of carotid intima-media thickness without increasing the risk of bleeding in patients with acute coronary syndrome during a 2-year follow-up

Heart and Vessels — Wed, 08 Dec 2010 18:09:48 +0100

Abstract Cilostazol, a phosphodiesterase III inhibitor, is known to have anti-proliferative activity. We investigated the effects of cilostazol 200 mg, in addition to aspirin 100 mg and clopidogrel 75 mg, on carotid intima-media thickness (IMT) progression during a 2-year follow-up period in patients with acute coronary syndrome (ACS) requiring stent implantation. Patients with ACS (n = 130) were randomly assigned to the cilostazol group (n = 64) or the control group (n = 66). Longitudinal images of left and right carotid IMT were measured at baseline, at 6, 12, and 24 months using a 10-MHz linear vascular probe. The primary endpoint was to compare the changes in maximum carotid IMT at 2 years. Other parameters such as ...

Cilostazol Increases Skin Perfusion Pressure in Severely Ischemic Limbs

Angiology — Mon, 06 Dec 2010 00:00:00 +0100

Skin perfusion pressure (SPP) is a measure of peripheral circulation; low SPP (<40 mm Hg) indicates poor wound healing. Cilostazol is used to alleviate symptoms and improve walking distance in patients with peripheral artery disease (PAD), but its effect on SPP is unknown. We enrolled patients whose symptoms were Rutherford class 3 or 4 and whose SPP was <40 mm Hg. We analyzed patient symptoms, ankle-brachial index (ABI), and SPP before and 1 month after treatment with cilostazol. We analyzed 20 legs of 14 patients. Cilostazol improved symptoms in 12 legs. The average heart rate increased from 76 ± 16 to 84 ± 20 beats/min (P < .05). Cilostazol did not increase the ABI but caused a significant increase in the SPP from 24.5 ± 8.88 to 42.8 ± 21.0 mm Hg (P ...

[In Context] September, 2010

Lancet Neurology — Wed, 17 Nov 2010 10:50:18 +0100

Neuropathic pain (Review, August)Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol 2010; 9: 807–19.Drugs for Alzheimer's disease (Review, July)Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M. Alzheimer's disease: clinical trials and drug development. Lancet Neurol 2010; 9: 702–16.Cilostazol for prevention of secondary stroke (Articles, October)Shinohara Y, Katayama Y, Uchiyama S, et al, for the CSPS 2 group. Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial. (Source: Lancet Neurology)

Cilostazol augments the inhibition of platelet aggregation in clopidogrel low‐responders

Journal of Thrombosis and Haemostasis — Mon, 01 Nov 2010 00:00:00 +0100

(Source: Journal of Thrombosis and Haemostasis)

The Phosphodiesterase Inhibitor Cilostazol Induces Regression of Carotid Atherosclerosis in Subjects With Type 2 Diabetes Mellitus Principal Results of the Diabetic Atherosclerosis Prevention by Cilostazol (DAPC) Study: A Randomized Trial

Journal of Vascular Surgery — Mon, 01 Nov 2010 00:00:00 +0100

Conclusion: Cilostazol provides greater inhibition of progression of carotid intima-medial thickness than aspirin in patients with type 2 diabetes mellitus. Summary: It appears patients with diabetes without previous myocardial infarction have as high a risk of myocardial infarction as patients without diabetes and previous myocardial infarction (Haffner SM, et al, N Engl J Med 1998;339:229-34). On the basis of this, some have advocated that primary prevention in patients with diabetes may be indicated. Guidelines suggest that individuals with risk factors for coronary heart disease, such as diabetes mellitus, should take aspirin for primary and secondary prevention, although the ability of aspirin to effectively serve as a primary preventive agent is controversial (American Diabetes Asso...

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Cilostazol Response Was High in Diabetes Patients

Family Practice News — Mon, 01 Nov 2010 00:00:00 +0100

Major Finding: Adding cilostazol, 100 mg twice daily, to a standard regimen of dual-antiplatelet therapy with aspirin and clopidogrel cut platelet reactivity by an average of 23% in patients with diabetes, and by an average of 15% in patients without diabetes, statistically significant differences. (Source: Family Practice News)

PLETAL (Cilostazol) Tablet [Otsuka America Pharmaceutical, Inc.]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Thu, 28 Oct 2010 05:00:00 +0100

Updated Date: Oct 28, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Long-term effects of cilostazol on the prevention of macrovascular disease in patients with type 2 diabetes mellitus

Diabetes Research and Clinical Practice — Mon, 11 Oct 2010 00:00:00 +0100

Abstract: We analyzed the medical records of 884 type 2 DM patients who were taking different antiplatelet agents for more than 2 years. Based on the records, occurrences of cardiovascular events for 10 years were evaluated. The composite disease-free survival rate for cilostazol monotherapy group was similar to aspirin subgroup (p=0.133). (Source: Diabetes Research and Clinical Practice)

Cilostazol Is an Effective Antiplatelet Drug Following Stroke

AccessMedicine Updates — Sun, 10 Oct 2010 03:30:01 +0100

(Source: AccessMedicine Updates)

Determination of the Prevalence of Aspirin and Clopidogrel Resistances in Patients with Coronary Artery Disease by using Various Platelet-function Tests.

The Korean Journal of Laboratory Medicine — Thu, 30 Sep 2010 23:00:00 +0100

CONCLUSIONS: The clinical usefulness of the different assays for the correct classification of patients in terms of antiplatelet resistance remains unclear. Further studies are required to determine the best method for correlating the occurrences of adverse ischemic events. PMID: 20890076 [PubMed - in process] (Source: The Korean Journal of Laboratory Medicine)

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[Reflection and Reaction] Secondary prevention of stroke: can we do better than aspirin?

Lancet Neurology — Thu, 30 Sep 2010 23:00:00 +0100

Meta-analyses have reported that antiplatelet therapy is associated with a 25% reduction in recurrent ischaemic stroke in patients with a previous stroke or transient ischaemic attack. one such drug is cilostazol, which inhibits the phosphodiesterase 3A enzyme and uptake of adenosine and has been shown to inhibit platelet aggregation. (Source: Lancet Neurology)

[Articles] Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial

Lancet Neurology — Thu, 30 Sep 2010 23:00:00 +0100

Cilostazol seems to be non-inferior, and might be superior, to aspirin for prevention of stroke after an ischaemic stroke, and was associated with fewer haemorrhagic events. Therefore, cilostazol could be used for prevention of stroke in patients with non-cardioembolic stroke. (Source: Lancet Neurology)

Pregnancy and Short‐Coupled Torsades de Pointes

Pacing and Clinical Electrophysiology : PACE — Thu, 30 Sep 2010 23:00:00 +0100

This 24‐year‐old woman had incessant polymorphic ventricular tachycardia (PVT) during week 24 of her pregnancy and received over 200 implantable cardioverter‐defibrillator discharges. She failed to respond to quinidine, magnesium, isoproterenol, amiodarone, esmolol, and cilostazol during her PVT storm, although her dramatic response to verapamil was consistent with the diagnosis of short‐coupled variant of torsades de pointes. The case illustrated the utility of extracorporeal membrane oxygenation during refractory PVT, while attempting diagnostic and therapeutic pharmacologic maneuvers. (PACE 2010; 1–3) (Source: Pacing and Clinical Electrophysiology : PACE)

Protecting against ischemia‐reperfusion injury: antiplatelet drugs, statins, and their potential interactions

Annals of the New York Academy of Sciences — Thu, 30 Sep 2010 23:00:00 +0100

Statins and antiplatelet agents are currently used as therapeutic agents for patients with acute myocardial infarction. Statins limit myocardial infarct size by activating phosphatidylinositol‐3‐kinase (PI3K), ecto‐5′‐nucleotidase, Akt/endothelial nitric oxide synthase (eNOS), and the downstream effectors inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2). Inhibition of PI3K, adenosine receptors, eNOS, iNOS, or COX‐2 abrogates the protective effects of statins. At >5 mg/kg, aspirin attenuates the myocardial infarct‐size‐limiting effect of statins. In contrast, the combination of low‐dose atoravastatin with either the phosphodiesterase‐III inhibitor cilostazol or the adenosine reuptake inhibitor dipyridamole synergistically limits infarct size. Low�...

Similar Efficacy, Less Bleeding With Cilostazol vs Aspirin for Recurrent Stroke Prevention: CSPS 2 Published

Medscape Nurses Headlines — Wed, 29 Sep 2010 14:00:00 +0100

Final results of the CSPS 2 trial, presented earlier this year, show a similar efficacy but fewer hemorrhagic events with cilostazol vs aspirin. Medscape Medical News (Source: Medscape Nurses Headlines)

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Cilostazol ‘might be superior’ to aspirin for secondary stroke prevention

MedWire News - Stroke — Tue, 21 Sep 2010 08:06:56 +0100

Cilostazol is noninferior to aspirin for recurrent stroke prevention and is associated with less bleeding risk, say the CSPS 2 investigators. (Source: MedWire News - Stroke)

[Reflection and Reaction] Secondary prevention of stroke: can we do better than aspirin?

Lancet Neurology — Sun, 19 Sep 2010 23:00:00 +0100

Meta-analyses have reported that antiplatelet therapy is associated with a 25% reduction in recurrent ischaemic stroke in patients with a previous stroke or transient ischaemic attack. Over the past few years, trials have assessed the efficacy and safety of antiplatelet drugs other than aspirin; one such drug is cilostazol, which inhibits the phosphodiesterase 3A enzyme and uptake of adenosine and has been shown to inhibit platelet aggregation. (Source: Lancet Neurology)

[Articles] Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial

Lancet Neurology — Sun, 19 Sep 2010 23:00:00 +0100

Platelets have a pivotal role in the pathogenesis of atherothrombosis, and findings of randomised trials and meta-analyses have shown the efficacy of antiplatelet therapies for secondary prevention after ischaemic stroke. Comparisons of several antiplatelet regimens have shown statistically significantly different outcomes, though only marginal clinical benefit, in stroke prevention, and few regimens have proven significantly more effective than has aspirin alone. Dual antiplatelet therapy has been intensively studied, and in the Management of Atherothrombosis with Clopidogrel in High-risk patients (MATCH) and Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilisation, Management, and Avoidance (CHARISMA) trials combined aspirin and clopidogrel was not more effective for reducti...

Cilostazol matches aspirin’s effectiveness in preventing secondary stroke

MD Consult: News: Top Stories — Tue, 14 Sep 2010 00:00:00 +0100

Read the full story on MD Consult: Cilostazol matches aspirin’s effectiveness in preventing secondary stroke (Source: MD Consult: News: Top Stories)

Cilostazol As Good As Aspirin for Stroke Prevention

Modern Medicine — Mon, 13 Sep 2010 23:00:00 +0100

The antiplatelet drug cilostazol is non-inferior, and possibly superior, to aspirin for secondary stroke prevention, and is associated with fewer hemorrhagic events, according to research from the second Cilostazol Stroke Prevention Study published online Sept. 11 in The Lancet Neurology. (Source: Modern Medicine)

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Cilostazol Seems to Outperform Aspirin in Preventing Secondary Stroke

Physician's First Watch current issue — Mon, 13 Sep 2010 12:06:28 +0100

(Source: Physician's First Watch current issue)

Cilostazol could cut repeat stroke rate

HealthcareRepublic Independent Nurse News — Mon, 13 Sep 2010 00:01:00 +0100

Using cilostazol, rather than aspirin, to prevent repeat stroke is associated with fewer bleeding events and may be more effective, a study has found. (Source: HealthcareRepublic Independent Nurse News)

Cilostazol may have similar benefits as aspirin for secondary stroke prevention

NeLM - News — Sun, 12 Sep 2010 23:00:00 +0100

This study aimed to determine whether it was non-inferior to aspirin as secondary prophylaxis in patients with non-cardioembolic ischaemic stroke. Participants were Japanese adults aged 20 to 79 who had suffered an ischaemic stroke within the previous 26 weeks. They were randomised to receive cilostazol 100mg bd or aspirin 81mg daily and followed up for the primary outcome of any stroke (cerebral infarction, cerebral haemorrhage, or subarachnoid haemorrhage). Serious bleeding (cerebral haemorrhage, subarachnoid haemorrhage, or haemorrhage requiring hospital admission) was a major safety outcome. Over a period of 34 months, 2,757 patients were enrolled into the trial (cilostazol 1,379, aspirin 1,378), of whom 2,672 (1,337 ... (Source: NeLM - News)

Enhanced platelet inhibition by adjunctive cilostazol to dual antiplatelet therapy after drug-eluting stent implantation for complex lesions.

Thrombosis and Haemostasis — Sun, 12 Sep 2010 23:00:00 +0100

Authors: Jeong YH, Park Y, Kim IS, Yun SE, Kang MK, Hwang SJ, Kwak CH, Hwang JY PMID: 20838742 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)

Second Strokes Less Common With Cilostazol (CME/CE)

MedPage Today Cardiovascular — Sat, 11 Sep 2010 03:13:00 +0100

(MedPage Today) -- The antiplatelet agent cilostazol (Pletal) appeared significantly more effective than aspirin for secondary prevention of strokes and was associated with fewer major bleeding events in a Japanese study. (Source: MedPage Today Cardiovascular)

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Cilostazol prevents amyloid β peptide25‐35‐induced memory impairment and oxidative stress in mice

British Journal of Pharmacology — Tue, 31 Aug 2010 23:00:00 +0100

(Source: British Journal of Pharmacology)

Triple antiplatelet therapy reduces ischemic events after drug-eluting stent implantation: Drug-Eluting stenting followed by Cilostazol treatment REduces Adverse Serious cardiac Events (DECREASE registry)

American Heart Journal — Tue, 31 Aug 2010 23:00:00 +0100

We appreciate the work by Lee et al that answered in part our concern raised in the Korea Acute Myocardial Infarction Registry regarding acute and subacute stent thrombosis with drug-eluting stent (DES) for those undergoing percutaneous coronary intervention on cilostazol-based triple therapy. Apparently, the rate of stent thrombosis with DES was lower in the triple antiplatelet therapy group than that in the dual antiplatelet therapy group in propensity-matched patients during 1-year follow-up (0.1% vs 0.8%, P = .0192). As with the comments of Chen et al made in the Korea Acute Myocardial Infarction Registry trial that the mortality benefit of triple antiplatelet therapy was obtained mainly within 30 days after ST-segment elevation myocardial infarction, we found that the benefit of cilos...

Response to letter regarding the article “Triple antiplatelet therapy reduces ischemic events after drug-eluting stent implantation; Drug-Eluting stenting followed by Cilostazol treatment REduces Adverse Serious cardiac Events (DECREASE registry)”

American Heart Journal — Tue, 31 Aug 2010 23:00:00 +0100

We appreciate Dr Lin's interest and comment to our work. In our registry study, cilostazol administration after stenting was usually recommended in patients with high risk of stent thrombosis (for at least 1 month) or restenosis (for 6 months). Clopidogrel was used for at least 6 months after stenting. Therefore, the duration of cilostazol administration is shorter than that of clopidogrel. The incidence of stent thrombosis was decreased within 2 months because of cilostazol treatment with a mean duration of 77.4 ± 88.1 days in the triple antiplatelet therapy group, and this early benefit was maintained up to 12 months. However, the optimal duration of triple antiplatelet therapy could not be determined because the study was underpowered to analyze those events of very low incidence. (Sou...

Office Management of Peripheral Arterial Disease

The American Journal of Medicine — Fri, 27 Aug 2010 06:37:43 +0100

Abstract: Patients with peripheral arterial disease are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease. Smoking should be stopped, and hypertension, diabetes mellitus, and dyslipidemia should be treated. Statins reduce the incidence of intermittent claudication and increase exercise duration until the onset of intermittent claudication in patients with peripheral arterial disease and hypercholesterolemia. Antiplatelet drugs, such as aspirin or clopidogrel, angiotensin-converting enzyme inhibitors, and statins, should be given to all patients with peripheral arterial disease. Beta-blockers should be given if coronary artery disease is present. Exercise rehabilitation programs and cilostazol improve exercise time until the onse...

Controversies and future perspectives of antiplatelet therapy in secondary stroke prevention.

J Cell Mol Med — Tue, 24 Aug 2010 23:00:00 +0100

Authors: Weber R, Diener HC Abstract Antiplatelet agents are a cornerstone in the treatment of acute arterial thrombotic events and in the prevention of thrombus formation. However, existing antiplatelet agents (mainly aspirin, the combination of aspirin and dipyridamole and clopidogrel) reduce the risk of vascular events only by about one quarter compared with placebo. As a consequence, more efficacious antiplatelet therapies with a reduced bleeding risk are needed. We give an overview of several new antiplatelet agents that are currently investigated in secondary stroke prevention: ADP receptor antagonists, cilostazol, sarpogrelate, terutroban and SCH 530348. There are unique features in secondary stroke prevention that have to be taken into account: ischemic stroke is a heterogeneou...

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Study design and rationale of 'Influence of Cilostazol-based triple anti-platelet therapy on ischemic complication after drug-eluting stent implantation (CILON-T)' study: A multicenter randomized trial evaluating the efficacy of Cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease

Trials — Mon, 23 Aug 2010 23:00:00 +0100

DiscussionCILON-T trial will give powerful insight into whether triple anti-platelet therapy is superior to dual anti-platelet therapy in reducing ischemic events and platelet reactivity in the real-world unselected patients treated with drug-eluting stent for coronary heart disease. Also, it will verify the laboratory and clinical significance of drug interaction between lipophilic statin and clopidogrel.Trial Registration. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT00776828). (Source: Trials)

cGMP-Dependent Protein Kinases and cGMP Phosphodiesterases in Nitric Oxide and cGMP Action.

Pharmacological Reviews — Sat, 21 Aug 2010 04:06:09 +0100

Authors: Francis SH, Busch JL, Corbin JD, Sibley D To date, studies suggest that biological signaling by nitric oxide (NO) is primarily mediated by cGMP, which is synthesized by NO-activated guanylyl cyclases and broken down by cyclic nucleotide phosphodiesterases (PDEs). Effects of cGMP occur through three main groups of cellular targets: cGMP-dependent protein kinases (PKGs), cGMP-gated cation channels, and PDEs. cGMP binding activates PKG, which phosphorylates serines and threonines on many cellular proteins, frequently resulting in changes in activity or function, subcellular localization, or regulatory features. The proteins that are so modified by PKG commonly regulate calcium homeostasis, calcium sensitivity of cellular proteins, platelet activation and adhesion, smooth muscle c...

Cilostazol enhances macrophage reverse cholesterol transport in vitro and in vivo

Atherosclerosis — Wed, 18 Aug 2010 23:00:00 +0100

Conclusions: These findings indicate that cilostazol might provide anti-atherosclerotic effects by promoting RCT through increased ABCA1/G1 expression in macrophages. (Source: Atherosclerosis)

Adding cilostazol further inhibits the platelet aggregation compared to the standard or high dose of clopidogrel in clopidogrel low responders

Journal of Thrombosis and Haemostasis — Sat, 31 Jul 2010 23:00:00 +0100

(Source: Journal of Thrombosis and Haemostasis)

A Combined Treatment for Acute Larger Lacunar-Type Infarction

Journal of Stroke and Cerebrovascular Diseases — Sun, 25 Jul 2010 23:00:00 +0100

This study was conducted to examine the efficacy of a combined treatment to prevent PMD or improve the functional outcome in patients with LLI. A total of 218 consecutive patients with LLI and motor lacunar syndrome were enrolled, including 138 patients with infarcts in the territory of the lenticulostriate artery and anterior choroidal artery (supratentrial group) and 80 patients with infarcts in the territory of the anterior pontine artery (pontine group). The prevalence of PMD and functional outcome represented by modified Rankin Scale (mRS) score at 1 month after ictus were compared between groups treated with a combined treatment approach consisting of cilostazol and edaravone (n = 100) and a conventional treatment approach (n = 118). The efficacy of the combined treatment provided in...

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Carriage of Cytochrome 2C19 Polymorphism Is Associated With Risk of High Post-Treatment Platelet Reactivity on High Maintenance-Dose Clopidogrel of 150 mg/day: Results of the ACCEL-DOUBLE (Accelerated Platelet Inhibition by a Double Dose of Clopidogrel According to Gene Polymorphism) Study

Journal of the American College of Cardiology: Cardiovascular Interventions — Mon, 19 Jul 2010 20:01:00 +0100

Conclusions Among PCI-treated patients receiving high-MD clopidogrel, carriage of CYP2C19 variant relates to increased PR and predicts risk of HPPR. (Adjunctive Cilostazol Versus High Maintenance-dose ClopidogrEL in Acute Myocardial Infarction [AMI] Patients According to CYP2C19 Polymorphism [ACCELAMI2C19]; NCT00915733; and Comparison of Platelet Inhibition With Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel According to Hepatic Cytochrome 2C19 Allele (CYP2C19) Polymorphism [ACCEL2C19]; NCT00891670). (Source: Journal of the American College of Cardiology: Cardiovascular Interventions)

Aspirin/cilostazol/heparin/ticlopidine: Retroperitoneal haematoma and bilateral iliopsoas haematomas in an elderly patient: case report

Reactions — Thu, 15 Jul 2010 06:25:48 +0100

(Source: Reactions)

Cilostazol Ameliorates Nephropathy in Type 1 Diabetic Rats Involving Improvement in Oxidative Stress and Regulation of TGF-beta and NF-kappaB.

Bioscience, Biotechnology, and Biochemistry — Tue, 06 Jul 2010 23:00:00 +0100

Authors: Lee WC, Chen HC, Wang CY, Lin PY, Ou TT, Chen CC, Wen MC, Wang J, Lee HJ Diabetic nephropathy is characterized as the progressive development of renal insufficiency in a setting of hyperglycemia. Previous studies indicate that reactive oxygen species (ROS) play an important role in high glucose-induced renal injury. Cilostazol was reported to lower the production of superoxide significantly in situ. We hypothesized that cilostazol administration in streptozotocin-induced diabetic rats exerts effects via improving oxidative stress. Male Sprague-Dawley rats were fed with cilostazol (5 mg/kg or 25 mg/kg) for 12 weeks after streptozotocin-induced diabetes mellitus. The results showed that cilostazol decreased reactive oxygen species activity significantly in the kidneys of diabeti...

Cilostazol Reverses Atherosclerosis in Diabetics

Medscape Diabetes Headlines — Fri, 02 Jul 2010 17:51:41 +0100

The phosphodiesterase inhibitor cilostazol induces regression of carotid atherosclerosis in patients with type 2 diabetes mellitus, Japanese researchers report in the June 15th issue of Circulation. Reuters Health Information (Source: Medscape Diabetes Headlines)