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Satoshi Takeo - One of the best experts on this subject based on the ideXlab platform.
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effects of Naftidrofuryl oxalate on microsphere embolism induced decrease in regional blood flow of rat brain
British Journal of Pharmacology, 1994Co-Authors: Keiko Miyake, Norio Takagi, Satoshi TakeoAbstract:1 The purpose of the present study was to determine whether Naftidrofuryl oxalate (Naftidrofuryl), a vasodilator, is capable of improving brain regional blood flow of animals in sustained ischaemia. 2 Cerebral ischaemia was induced by injecting 900 microspheres (48 μm in diameter) into the right internal carotid artery of rats. Cerebral blood flow of brain regions was measured by a hydrogen clearance method on the 3rd, 7th and 28th days after the onset of ischaemia. Ischaemic animals were treated with Naftidrofuryl, 15 mg kg−1 day−1 i.p., from the first to 28th day. 3 Microsphere-embolism caused a sustained decrease in cortical and striatal blood flow over a period of 28 days, whereas hippocampal blood flow was decreased on the 3rd day but not on the 7th or 28th day. On the 3rd day, the striatal and hippocampal but not cortical blood flow of Naftidrofuryl-treated, microsphere-embolized rats was higher than untreated rats. On the 7th and 28th days, the cortical and striatal blood flow of the treated and untreated animals did not differ. 4 Brain slices from microsphere-embolized rats contained areas, which were not stained with triphenyltetrazolium chloride (TTC), to a similar degree on the 3rd, 7th and 28th days, indicating the genesis of cerebral infarction. TTC-unstained areas of microsphere-embolized rats that had received Naftidrofuryl treatment were smaller than those of untreated rats on the 3rd and 7th days, but not on the 28th day. 5 The results suggest that Naftidrofuryl improves cerebral circulation impaired by microsphere-induced ischaemia and this higher level of cerebral blood flow of the treated animal may account for the delayed development of cerebral infarction.
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Effects of Naftidrofuryl oxalate on microsphere-induced changes in acetylcholine and amino acid content of rat brain regions
Experimental Brain Research, 1994Co-Authors: Taku Taguchi, Kouichi Tanonaka, Keiko Miyake, Norio Takagi, Manami Okada, Hiroki Kajihara, Satoshi TakeoAbstract:Effects of Naftidrofuryl oxalate (Naftidrofuryl) on neurotransmitter, acetylcholine, and amino acid content of brain regions following microsphere-induced cerebral embolism were examined to elucidate its possible therapeutic effects on ischemic brain. Rats received 900 microspheres (48 μm in diameter) via the right internal carotid artery, followed by ligation of the right common carotid artery; and histological and biochemical alterations were examined on the 3rd, 5th, and 28th days after embolism. The embolism induced increases in triphenyltetrazolium chloride-(TTC)-unstained areas and decreases in acetylcholine, glutamate, aspartate, and γ-aminobutyric acid (GABA) contents in the cerebral cortex, striatum, and hippocampus of the right hemisphere, suggesting that microsphere embolism causes severe damage to these brain regions. Hematoxylin-eosin staining of the right cortical sections after embolism showed degeneration and necrosis of nerve cells with chromatolytic nuclei and eosinophilic cytoplasm. Changes in neurotransmitters of the left hemisphere were relatively small. Treatment with Naftidrofuryl of the embolized rats with stroke-like symptoms took place from postoperative day 1 to 28. Treatment resulted in a reduction in TTC-unstained areas, less morphological damage to cerebral cortex on the 3rd and 5th days, and an appreciable restoration of acetylcholine content of three brain regions of the right hemisphere throughout the experiment, but restoration of neurotransmitter amino acids was observed to a smaller degree. The results suggest that Naftidrofuryl is capable of preventing the development of ischemia-induced, sustained damage to brain regions vulnerable to oxygen deficiency, particularly by improving impaired acetylcholine metabolism.
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beneficial effects of Naftidrofuryl oxalate on brain regional energy metabolism after microsphere induced cerebral embolism
Journal of Pharmacology and Experimental Therapeutics, 1992Co-Authors: K Miyake, Kouichi Tanonaka, Taku Taguchi, Norio Takagi, T Horiguchi, Satoshi TakeoAbstract:The present study was undertaken to elucidate the possible therapeutic effects of Naftidrofuryl on energy metabolism of brain regions impaired for extended periods by microsphere embolism. Nine hundred microspheres (48 microns in diameter) were injected into the right internal carotid artery of rats, and changes in their behavior and energy metabolism of the cortex, striatum and hippocampus of both hemispheres were determined with and without Naftidrofuryl treatment. Microsphere embolism induced increases in lactate, glucose and glycogen contents and decreases in ATP and creatine phosphate of these brain regions of the right hemisphere for up to 28 days after the operation, suggesting long-lasting cerebral ischemia or sustained damage to energy metabolism. These changes were gradually reversed with time after the operation. Microsphere-injected rats were treated twice a day with 15 mg/kg Naftidrofuryl, and their behavioral and metabolic protection were determined on the 3rd, 5th and 28th days after the operation. Treatment of embolized animals with Naftidrofuryl improved these variables appreciably on the 3rd and 28th days, but little on the 5th day. The improvement on the 3rd day was more evident in all brain regions monitored than that on the 28th day. The results suggest that Naftidrofuryl exerts beneficial effects on the energy metabolism of brains damaged by microsphere embolism, the mechanism of which may be due to protection against the development of embolism-induced derangement.
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Naftidrofuryl oxalate improves impaired brain glucose metabolism after microsphere-induced cerebral embolism in rats.
The Journal of pharmacology and experimental therapeutics, 1991Co-Authors: Satoshi Takeo, R. Tanonaka, K Miyake, Kouichi Tanonaka, Taku Taguchi, K. Kawakami, M Ono, M Hiramatsu, K OkanoAbstract:The present study was designed to elucidate possible therapeutic effects of Naftidrofuryl on the brain glucose metabolism after cerebral ischemia. Cerebral ischemia was induced by injecting 680 microspheres with a diameter of 48 microns into the right internal carotid artery of the rat. After ensuring the onset of symptoms of stroke on the first day after the operation, the rats were treated with intraperitoneal injections of 15 mg/kg Naftidrofuryl oxalate twice a day. The behavioral and metabolic changes of operated rats were monitored up to the 5th day after surgery. The symptoms gradually faded away, from the 3rd day on, after microsphere-induced cerebral embolism. Tissue glucose and glycogen greatly increased after cerebral embolism, suggesting embolism-induced inhibition of glycolysis. To elucidate which steps in the glycolytic catabolism are inhibited after cerebral ischemia, biochemical activities of the glycolytic enzymes in the Embden-Meyerhof pathway and tricarboxylic acid cycle were determined on the 3rd day after surgery. Enzyme activities of hexokinase, phosphofructokinase and pyruvate kinase were not inhibited, but rather increased slightly after cerebral embolism. Malate dehydrogenase activity in the brain mitochondria was markedly increased after microsphere-embolism, whereas other enzyme activities in the tricarboxylic acid cycle were never inhibited by the cerebral embolism. Treatment of Naftidrofuryl resulted in an appreciable reverse of the brain glucose and glycogen levels and a substantial recovery of altered enzyme activities to normal levels in the Embden-Meyerhof pathway and tricarboxylic acid cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
Gerard Stansby - One of the best experts on this subject based on the ideXlab platform.
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cost effectiveness of cilostazol Naftidrofuryl oxalate and pentoxifylline for the treatment of intermittent claudication in people with peripheral arterial disease
Angiology, 2014Co-Authors: Yang Meng, Hazel Squires, Emma Simpson, S Harnan, John Stevens, S Thomas, J A Michaels, Gerard Stansby, Mark E OdonnellAbstract:We assessed the cost-effectiveness of cilostazol, Naftidrofuryl oxalate, and pentoxifylline for intermittent claudication due to peripheral arterial disease (PAD) in adults whose symptoms continue despite a period of conventional management. A Markov decision model was developed to assess the lifetime costs and benefits of each vasoactive drug compared to no vasoactive drug and with each other. Regression analysis was undertaken to model the relationship between maximum walking distance and utility. Resource use data were sourced from the literature and sensitivity analyses were undertaken. Naftidrofuryl oxalate is more effective and less costly than cilostazol and pentoxifylline and has an estimated cost per quality-adjusted life year gained of around £6070 compared to no vasoactive drug. The analysis uses effectiveness evidence from a network meta-analysis. In contrast to previous guidelines recommending cilostazol, the analysis suggests that Naftidrofuryl oxalate is the only vasoactive drug for PAD which is likely to be cost-effective.
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systematic review of the efficacy of cilostazol Naftidrofuryl oxalate and pentoxifylline for the treatment of intermittent claudication
British Journal of Surgery, 2012Co-Authors: John Stevens, Hazel Squires, Emma Simpson, Yang Meng, S Harnan, J A Michaels, Steven M Thomas, Gerard StansbyAbstract:Background: A systematic review and network meta-analysis was undertaken to consider the evidence for the efficacy and tolerability of placebo, cilostazol, Naftidrofuryl oxalate and pentoxifylline in patients with intermittent claudication due to peripheral arterial disease (PAD). Methods: MEDLINE, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings, BIOSIS, National Research Register and MetaRegister databases were searched. Eligible studies were randomized controlled trials (RCTs) and published systematic reviews of patients with intermittent claudication due to PAD and whose symptoms persisted despite a period of conservative management. Study selection was conducted by one reviewer with involvement from a clinician. Data were extracted by one reviewer with no blinding to authors or journal, and checked by a second reviewer. Outcome measures were maximum walking distance (MWD) and pain-free walking distance (PFWD). Results: The review identified 1876 citations; 26 RCTs met the inclusion criteria for the systematic review. Eleven trials provided data relevant for the meta-analysis. Naftidrofuryl oxalate was ranked first for both MWD and PFWD (probability of 0·947 and 0·987, respectively, of being the best treatment) followed by cilostazol and pentoxifylline. For Naftidrofuryl oxalate, cilostazol and pentoxifylline, MWD increased by 60 (95 per cent credible interval 20 to 114) per cent, 25 (11 to 40) per cent and 11 (−1 to 24) per cent respectively relative to placebo, and PFWD increased by 49, 13 and 9 per cent. Conclusion: Naftidrofuryl oxalate and cilostazol are both effective treatments for claudication; Naftidrofuryl oxalate is likely to be the most effective, with minimal serious adverse events. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
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a systematic review and economic evaluation of cilostazol Naftidrofuryl oxalate pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease
Health Technology Assessment, 2011Co-Authors: Hazel Squires, Emma Simpson, Yang Meng, S Harnan, John Stevens, Ruth Wong, S Thomas, J A Michaels, Gerard StansbyAbstract:BACKGROUND: Peripheral arterial disease (PAD) is a condition in which there is blockage or narrowing of the arteries that carry blood to the legs and arms. It is estimated to affect around 4.5% of people aged between 55 and 74 years within the UK. The most common symptom of PAD is intermittent claudication (IC), characterised by pain in the legs on walking that is relieved with rest. OBJECTIVE: To assess the effectiveness and cost-effectiveness of cilostazol, Naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no vasoactive drugs, for IC due to PAD in adults whose symptoms continue despite a period of conventional management. DATA SOURCE: Electronic bibliographic databases were searched during April to June 2010 (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings Citation Index, BIOSIS Previews). REVIEW METHODS: Effectiveness outcomes sought were maximal walking distance (MWD), pain-free walking distance (PFWD), ankle-brachial pressure index, cardiovascular events, mortality, adverse events (AEs) and health-related quality of life (HRQoL). A narrative synthesis was provided for all outcomes and a network meta-analysis was undertaken for the walking distance outcomes. A Markov model was developed to assess the relative cost-effectiveness of the interventions from a NHS perspective over a lifetime. The model has three states: vasoactive drug treatment, no vasoactive drug treatment and death. Each 1-week cycle, patients may continue with the drug, discontinue the drug or die. Regression analysis was undertaken to model the relationship between MWD and utility so that a cost per quality-adjusted life-year (QALY) outcome measure could be presented. Univariate and probabilistic sensitivity analyses were undertaken. All costs and outcomes were discounted at 3.5%. RESULTS: Twenty-six randomised controlled trials were identified that met the inclusion criteria for the clinical effectiveness review. There was evidence that walking distance outcomes were significantly improved by both cilostazol and Naftidrofuryl oxalate; the 95% credible intervals for the difference from placebo in the logarithm mean change MWD from baseline were 0.108 to 0.337 and 0.181 to 0.762, respectively. It was not possible to include inositol nicotinate within the meta-analysis of MWD and PFWD owing to the lack of 24-month data; however, the shorter-term data did not suggest a significant effect. AEs were minor for all drugs and included headaches and gastrointestinal difficulties. The incidence of serious adverse events (SAEs), including cardiovascular events and mortality, was not increased by the vasoactive drugs compared with placebo; however, most studies had a relatively short follow-up time to address this outcome. HRQoL data were limited. Two studies of limited quality were identified within the review of cost-effectiveness. The de novo model developed suggests that Naftidrofuryl oxalate dominates cilostazol and pentoxifylline and has a cost per QALY gained of around £6070 compared with no vasoactive drug. This result is reasonably robust to changes within the key model assumptions. Inositol nicotinate was not included within the main analysis owing to lack of data. However, it is unlikely to be considered to be cost-effective due to its high acquisition cost (£900 vs £100-500 per year for the other drugs). CONCLUSIONS: Naftidrofuryl oxalate and cilostazol both appear to be effective treatments for this patient population, with minimal SAEs. However, Naftidrofuryl oxalate is the only treatment that is likely to be considered cost-effective. The long-term effectiveness is uncertain and hence a trial comparing cilostazol, Naftidrofuryl oxalate and placebo beyond 24 weeks would be beneficial. Outcomes associated with Naftidrofuryl oxalate could also be compared with those associated with supervised exercise programmes and angioplasty.
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a systematic review and economic evaluation of cilostazol Naftidrofuryl oxalate pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease
Health Technology Assessment, 2011Co-Authors: Hazel Squires, Emma Simpson, Yang Meng, S Harnan, John Stevens, Ruth Wong, S Thomas, J A Michaels, Gerard StansbyAbstract:Background Peripheral arterial disease (PAD) is a condition in which there is blockage or narrowing of the arteries that carry blood to the legs and arms. It is estimated to affect around 4.5% of people aged between 55 and 74 years within the UK. The most common symptom of PAD is intermittent claudication (IC), characterised by pain in the legs on walking that is relieved with rest. Objective To assess the effectiveness and cost-effectiveness of cilostazol, Naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no vasoactive drugs, for IC due to PAD in adults whose symptoms continue despite a period of conventional management. Data source Electronic bibliographic databases were searched during April to June 2010 (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings Citation Index, BIOSIS Previews). Review methods Effectiveness outcomes sought were maximal walking distance (MWD), pain-free walking distance (PFWD), ankle–brachial pressure index, cardiovascular events, mortality, adverse events (AEs) and health-related quality of life (HRQoL). A narrative synthesis was provided for all outcomes and a network meta-analysis was undertaken for the walking distance outcomes. A Markov model was developed to assess the relative cost-effectiveness of the interventions from a NHS perspective over a lifetime. The model has three states: vasoactive drug treatment, no vasoactive drug treatment and death. Each 1-week cycle, patients may continue with the drug, discontinue the drug or die. Regression analysis was undertaken to model the relationship between MWD and utility so that a cost per quality-adjusted life-year (QALY) outcome measure could be presented. Univariate and probabilistic sensitivity analyses were undertaken. All costs and outcomes were discounted at 3.5%. Results Twenty-six randomised controlled trials were identified that met the inclusion criteria for the clinical effectiveness review. There was evidence that walking distance outcomes were significantly improved by both cilostazol and Naftidrofuryl oxalate; the 95% credible intervals for the difference from placebo in the logarithm mean change MWD from baseline were 0.108 to 0.337 and 0.181 to 0.762, respectively. It was not possible to include inositol nicotinate within the meta-analysis of MWD and PFWD owing to the lack of 24-month data; however, the shorter-term data did not suggest a significant effect. AEs were minor for all drugs and included headaches and gastrointestinal difficulties. The incidence of serious adverse events (SAEs), including cardiovascular events and mortality, was not increased by the vasoactive drugs compared with placebo; however, most studies had a relatively short follow-up time to address this outcome. HRQoL data were limited. Two studies of limited quality were identified within the review of cost-effectiveness. The de novo model developed suggests that Naftidrofuryl oxalate dominates cilostazol and pentoxifylline and has a cost per QALY gained of around £6070 compared with no vasoactive drug. This result is reasonably robust to changes within the key model assumptions. Inositol nicotinate was not included within the main analysis owing to lack of data. However, it is unlikely to be considered to be cost-effective due to its high acquisition cost (£900 vs £100–500 per year for the other drugs). Conclusions Naftidrofuryl oxalate and cilostazol both appear to be effective treatments for this patient population, with minimal SAEs. However, Naftidrofuryl oxalate is the only treatment that is likely to be considered cost-effective. The long-term effectiveness is uncertain and hence a trial comparing cilostazol, Naftidrofuryl oxalate and placebo beyond 24 weeks would be beneficial. Outcomes associated with Naftidrofuryl oxalate could also be compared with those associated with supervised exercise programmes and angioplasty. Source of funding The National Institute for Health Research Health Technology Assessment programme.
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effect of Naftidrofuryl and aspirin on platelet aggregation in peripheral vascular disease
in Vivo, 1993Co-Authors: M A Barradas, Gerard Stansby, G Hamilton, D P MikhailidisAbstract:Platelet aggregation in whole blood (WB) was assessed in healthy subjects and in patients with peripheral vascular disease (PVD) using a WB-free platelet counting (WB-FPC) method. Aggregation induced by stirring and platelet agonists was significantly enhanced in PVD patients. WB-FPC aggregation induced by 5-HT was diminished significantly by incubation with Naftidrofuryl (NAF) in WB of PVD patients. In contrast, aspirin (acetylsalicylic acid; ASA), added in vitro, did not significantly affect 5-HT or stirring-induced WB-PFC aggregation in PVD patients. Furthermore, 5-HT-induced WB-FPC was inhibited by NAF in blood collected from PVD patients that were taking low dose aspirin. These findings suggest that NAF may be of benefit to patients with hyperaggregable platelets and elevated plasma 5-HT concentrations, factors thought to predispose to thrombotic complications.
M Mosnier - One of the best experts on this subject based on the ideXlab platform.
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Naftidrofuryl driven regulation of endothelial icam 1 involves nitric oxide
Free Radical Biology and Medicine, 2003Co-Authors: A Marconi, M Mosnier, S Darquenne, A Boulmerka, Patrizia DalessioAbstract:Abstract Naftidrofuryl is a selective inhibitor of the 5-HT2 receptor expressed on human endothelial cells. This drug has been used over the years to cope with cerebral or peripheral ischemic accidents; however, no clear mechanism of action of this molecule has been highlighted to explain its vascular effects. In the present work, we demonstrate that the involvement of nitric oxide can account for the effects of Naftidrofuryl. Indeed, Naftidrofuryl potently inhibited the TNF-α-triggered increase of intercellular adhesion molecule-1 (ICAM-1) expression as well as stress fiber formation in human umbilical vein endothelial cells (HUVEC). Moreover, Naftidrofuryl induced the expression of type II nitric oxide synthase (NOS II) messenger and protein, leading to a noticeable increase in nitric oxide synthesis. Furthermore, using the specific NOS II inhibitor 1400W, we verified that the observed effects of Naftidrofuryl were NOS II-dependent. The biology of nitric oxide accounts for the reduction of the vasospasm associated with stroke and the strong inhibition of platelet aggregation. In conclusion, our work provides evidence for the inhibition of leukocyte recruitment by downregulation of CD54/ICAM-1, an additional key factor to be dealt with during thrombotic accidents. Importantly, it also highlights a novel NOS II-dependent mechanism of action for Naftidrofuryl.
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effet du Naftidrofuryl sur la distance de marche physiologique chez des patients au stade de claudication intermittente
Annales De Cardiologie Et D Angeiologie, 2001Co-Authors: H Boccalon, Philippe Lehert, M MosnierAbstract:Resume L'efficacite et la tolerance du Naftidrofuryl ont ete largement demontrees lors de nombreuses etudes realisees en double-aveugle versus placebo chez des patients presentant une claudication intermittente, selon les recommandations europeennes qui preconisent l'utilisation du tapis roulant. Objectif – Le but de cette etude est de s'affranchir de ces conditions tres standardisees pour apprecier le reel benefice apporte par la therapeutique dans des conditions de marche naturelle. Methodes – Les patients selectionnes, des deux sexes, âges de 40 a 80 ans, avec un IPS compris entre 0,60 et 0,90, presentant une claudication intermittente ont ete randomises et suivis durant une annee. La posologie du Naftidrofuryl etait de 600 mg/j. Le critere principal etait la distance de marche indolore et maximale parcourue. Cette distance a ete mesuree a quatre reprises, a l'inclusion, et apres trois, six et 12 mois, grâce a un appareil (PADHOC ® ) utilisant une technique ultrasonique. Resultats – 182 patients ont ete randomises et 168 sont entres dans l'analyse en intention de traitement. Les deux groupes etaient comparables pour l'ensemble des donnees demographiques, a l'exclusion des diabetiques, dont le pourcentage etait plus eleve dans le groupe Naftidrofuryl. Apres un an de traitement, les patients appartenant au groupe Naftidrofuryl ont augmente leur distance de marche maximale de 74 % (moyenne geometrique), ceux du groupe placebo de 1 % ( p p Conclusion – Il s'agit de la premiere etude qui apprecie l'amelioration de la distance de marche, en condition ambulatoire. Cette evaluation permet une meilleure appreciation du reel benefice pour le patient.
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efficacy of Naftidrofuryl in patients with vascular or mixed dementia results of a multicenter double blind trial
Clinical Therapeutics, 2000Co-Authors: Jeanpaul Emeriau, Philippe Lehert, M MosnierAbstract:Abstract Background Dementia is a cerebral disorder resulting in a progressive deterioration of intellectual function that compromises the patient's ability to function. The diagnostic criteria for dementia are primarily clinical and are based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition . The Hachinski score and computed tomography of the brain help distinguish between degenerative and vascular dementias. Objective This study examined the efficacy of Naftidrofuryl in patients with vascular or mixed dementia. Methods This multicenter, randomized, double-blind study compared Naftidrofuryl 600 mg/d with placebo for 1 year in patients with vascular or mixed dementia. A preliminary 2-month washout period allowed selection of patients who were compliant with treatment. The end point was change in the scores on the Alzheimer Disease Assessment Scale cognitive subscale and the Mini-Mental State Examination. Results Eighty-four patients were assessable on an intent-to-treat basis, and 74 were assessable for the per-protocol analysis (on-treatment). Statistically significant improvements in cognitive and global function were observed in patients receiving Naftidrofuryl. Naftidrofuryl was well tolerated, and produced no clinically significant abnormalities in laboratory test results. Conclusion The results of this study suggest that Naftidrofuryl is effective and well tolerated in treating the symptoms of vascular and mixed dementia.
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effect of Naftidrofuryl on platelet aggregation in plasma from aspirin treated patients an in vitro study
Clinical Hemorheology and Microcirculation, 2000Co-Authors: Le C Devehat, T Khodabandehlou, M MosnierAbstract:This study concerns an in vitro evaluation of the effect of Naftidrofuryl on platelet aggregation in plasma of 15 diabetic patients, who were being treated with aspirin, and who were suffering from chronic arterial disease of the lower limbs. Platelet aggregation, induced either spontaneously or by aggregating agents, was measured in platelet-rich plasma (PRP). The results show that serotonin (5-HT)- and adenosine 5'-diphosphate (ADP)-induced platelet aggregation significantly decreased after addition of Naftidrofuryl. Decreases were achieved with Naftidrofuryl at a low dose (0.06 μM) and became more marked with Naftidrofuryl at higher concentrations. In contrast, Naftidrofuryl did not appear to modify routinely spontaneous platelet aggregation. These results show an in vitro antiaggregating effect of Naftidrofuryl on platelets of aspirinized patients. However, the clinical interest of a such coadministration of Naftidrofuryl and aspirin in patients, has still to be confirmed in a double blind randomized trial.
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Evaluation of the efficacy and tolerance of Naftidrofuryl in patients presenting with exertional angina. Multicenter double-blind versus placebo study
Annales de cardiologie et d'angeiologie, 1999Co-Authors: M Mosnier, Philippe LehertAbstract:Le Naftidrofuryl, par ses proprietes d'une part anti 5-HT 2 vasculaires et plaquettaires, d'autre part metaboliques, permet de lutter de maniere specifique contre les phenomenes ischemiques locaux. Une de ses indications princeps est le traitement de la claudication intermittente ; or nous savons que l'arteriopathie peripherique est le stigmate d'une maladie arterielle diffuse, avec des localisations coronaires particulierement meurtrieres. Des travaux recents impliquent de plus en plus la serotonine (5-HT) dans les processus ischemiques coronariens. La superposition de ces donnees physiopathologiques et les caracteristiques de cette molecule nous ont conduit a evaluer la protection coronarienne, qui pourrait etre assuree par le Naftidrofuryl, et sa tolerance. Cette etude multicentrique controlee en double-aveugle contre placebo porte sur une duree de 1 mois. Les criteres d'inclusion comprennent un angor stable avec epreuve d'effort positive electriquement, malgre un traitement anti-angineux soit par β-bloquant ou par inhibiteur calcique. Elle porte sur 51 patients; le suivi comporte un bilan clinique et une epreuve d'effort a l'inclusion et a 1 mois. A l'inclusion, les groupes sont comparables. Les resultats montrent globalement une amelioration plus importante du Naftidrofuryl par rapport au traitement de reference pour l'ensemble des parametres etudies. Les differences se revelent significatives au profit du groupe verum pour le delai d'apparition du sous-decalage de ST, le palier maximal atteint, le nombre d'epreuves d'effort negativees, l'appreciation globale du patient. Il n'a ete note par ailleurs aucun probleme d'interaction avec les therapeutiques associees, en particulier les β-bloquants, inhibiteurs calciques ou anti-arythmiques. Cette etude montre que le Naftidrofuryl permet une amelioration des parametres ergometriques et notamment un recul du seuil ischemique a l'effort.
Philippe Lehert - One of the best experts on this subject based on the ideXlab platform.
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Naftidrofuryl for intermittent claudication
Cochrane Database of Systematic Reviews, 2012Co-Authors: Philippe Lehert, T De Backer, Robert Vander Stichele, L Van BortelAbstract:Background : Lifestyle changes and cardiovascular prevention measures are a primary treatment for intermittent claudication (IC). Symptomatic treatment with vasoactive agents (Anatomic Therapeutic Chemical Classification (ATC) for medicines from the World Health Organisation class CO4A) is controversial. Objectives : To evaluate evidence on the efficacy and safety of oral Naftidrofuryl (ATC CO4 21) versus placebo on the pain-free walking distance (PFWD) of people with IC by using a meta-analysis based on individual patient data (IPD). Search strategy : The Cochrane Peripheral Vascular Diseases Group searched their Trials Register (last searched December 2007) and CENTRAL (last searched 2007, Issue 4). We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts, the Science Citation Index and contacted the authors and checked the reference lists of retrieved articles. We asked the manufacturing company for IPD. Selection criteria : We included only randomized controlled trials (RCTs) with low or moderate risk of bias for which the IPD were available. Data collection and analysis : We collected data from the electronic data file or from the case report form and checked the data by a statistical quality control procedure. All randomized patients were analyzed following the intention-to-treat (ITT) principle. The geometric mean of the relative improvement in PFWD was calculated for both treatment groups in all identified studies. The effect of the drug was assessed compared with placebo on final walking distance (WDf) using multilevel and random-effect models and adjusting for baseline walking distance (WD0). For the responder analysis, therapeutic success was defined as an improvement of walking distance of at least 50%. Main results : We included seven studies in the IPD (n = 1266 patients). One of these studies (n = 183) was only used in the sensitivity analysis so that the main analysis included 1083 patients. The ratio of the relative improvement in PFWD (Naftidrofuryl compared with placebo) was 1.37 (95% confidence interval (CI) 1.32 to 1.51, P < 0.001). The absolute difference in responder rate, or proportion successfully treated, was 22.3% (95% CI 17.1% to 27.6%). The calculated number needed to treat was 4.5 (95% CI 3.6 to 5.8). Authors' conclusions : Naftidrofuryl has a statistically significant and clinically meaningful effect of improving walking distance in the six months after initiation of therapy for people with intermittent claudication. Access by researchers to data from RCTs that is suitable for IPD analysis should be possible through repositories of data from pharmacological trials. Regular formal appraisal of the balance of risk and benefit is needed for older pharmaceutical products. Naftidrofuryl for intermittent claudication : Patients with narrowed arteries of the lower limbs may be hampered by pain in their calves after relatively short walks. This limits the distance they can walk, and hence their quality of life. This is a sure sign of atherosclerosis. These patients are at greater risk of cardiovascular death and should take preventive measures. The symptoms of the disease can be alleviated by smoking cessation and exercise. The question is whether specific drugs such as Naftidrofuryl also reduce symptoms, more than placebo. To answer the question, we collected all published reports of randomized trials where the drug was compared with placebo. In addition, we went back to the original data of individual patients and made one big database with all data from all patients from all trials. We included seven studies with a total of 1266 patients. The improvement of pain-free walking distance was 37% larger in the Naftidrofuryl group than the improvement observed in the placebo group. In the Naftidrofuryl group 55% of the patients improved by more than 50%, compared with 30% of patients on placebo. Naftidrofuryl 200 mg (taken three times a day by mouth) improved walking distance in the six months after the start of therapy.
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Naftidrofuryl for intermittent claudication meta analysis based on individual patient data
BMJ, 2009Co-Authors: T De Backer, Philippe Lehert, Vander R Stichele, L Van BortelAbstract:Objective To assess the efficacy of Naftidrofuryl compared with placebo in treating the symptoms of intermittent claudication. Design Meta-analysis based on individual patient data. Data sources Medline, International Pharmaceutical Abstracts, Embase, Science Citation Index, and the Cochrane trial registers. Reference lists of retrieved articles were checked. Authors and companies were approached for additional information and individual patient data. Inclusion criteria Double blind, randomised controlled trials in patients with intermittent claudication receiving oral Naftidrofuryl or placebo and with pain-free walking distance as primary outcome. Data collection Individual patient data were collected from electronic data or from case report forms and checked for integrity. Analysis All randomised patients were analysed following the intention to treat principle. Efficacy was assessed by the ratio of geometric mean of the relative improvement in pain-free walking distance after use of Naftidrofuryl compared with placebo. In the analysis of responders, therapeutic success was defined as an improvement of walking distance at baseline by at least 50%. Results In total, 1266 patients were randomised (1083 in the main analysis). The ratio of relative improvement in pain-free walking distance after use of Naftidrofuryl compared with placebo was 1.37 (95% confidence interval 1.27 to 1.49). The difference in response rate was 22.3% (95% confidence interval 17.1% to 27.6%) and the number needed to treat for relief of symptoms during six months of treatment was 4.48 (95% confidence interval 3.62 to 5.85). Conclusion This meta-analysis of individual patient data provides evidence that Naftidrofuryl has a clinically meaningful effect compared with placebo in improving walking distance in patients with intermittent claudication.
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Naftidrofuryl for intermittent claudication a meta analysis
22nd International conference on Pharmacoepidemiology and therapeutic Risk Management August 24-27, 2006Co-Authors: Vander R Stichelen, Philippe Lehert, L Vanbortel, T DebackerAbstract:Objectives: Assessing the efficacy of a pharmaceutical agent throughout an Individual Patient Data Meta-analysis IPD-MA. Of 7 available studies, 6 were considered as acceptable, for a total of 1266 randomized patients. We were able to match all the Previous results of original publications. The geometric mean ratio of CD improvement Naftidrofuryl/placebo was 1.41 (95%CI 1.32-1.51, p<0.001), and the Number Needed to Treat 5, with results robust to sensitivity analysis. The difficulties and potential of bias of performing IPD in the pharmaceutical sector will be discussed. The implications of the evidence that Naftidrofuryl has a clinically meaningful effect in improvement of claudication distance will be discussed in the light of subjective outcomes and hard endpoints.
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the effect of Naftidrofuryl in peripheral blood pressures in patients with intermittent claudication a random model meta analysis
International Angiology, 2003Co-Authors: P Lacroix, Philippe Lehert, H BoccalonAbstract:The effect of Naftidrofuryl in peripheral blood pressures in patients with Intermittent Claudication has been assessed throughout a Random Model Meta-analysis. Anckle to Brachial Index was significantly different in the studied treatment group compared with placebo.
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the effect of Naftidrofuryl in patients with intermittent claudication an assessment in general practice using the clau s short form
International Angiology, 2003Co-Authors: Philippe LehertAbstract:Clau-S questionnaire has recently be considered as one of the best Qol specific instruments for PAD. A 9-items short version was derived for use in General practice. a cohort of 780 patients was prospectively followed during 6 months where each patient received a treatment known to increase QoL (Naftidrofuryl 600mg daily). A secondary objective was to study the effect of physical exercise PE and smoking cessation SC on improvement in QoL, together with the use of a pharmacological agent. Results were: The sample was representative of PAD Stage II population, for general score as well as physical PH and mental MT subscores, internal consistency was constantly <.85, and estimated Standard Error or Measurement for MT was 6.59 (95% Upper CI=10.87). Thus the short scale preserves the same reliability as the whole Clau-S. Sensitivity to change was estimated by Effect sizes ES=.89, a value at least as large as earlier studies on both QoL and Walking distances.
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cost effectiveness of cilostazol Naftidrofuryl oxalate and pentoxifylline for the treatment of intermittent claudication in people with peripheral arterial disease
Angiology, 2014Co-Authors: Yang Meng, Hazel Squires, Emma Simpson, S Harnan, John Stevens, S Thomas, J A Michaels, Gerard Stansby, Mark E OdonnellAbstract:We assessed the cost-effectiveness of cilostazol, Naftidrofuryl oxalate, and pentoxifylline for intermittent claudication due to peripheral arterial disease (PAD) in adults whose symptoms continue despite a period of conventional management. A Markov decision model was developed to assess the lifetime costs and benefits of each vasoactive drug compared to no vasoactive drug and with each other. Regression analysis was undertaken to model the relationship between maximum walking distance and utility. Resource use data were sourced from the literature and sensitivity analyses were undertaken. Naftidrofuryl oxalate is more effective and less costly than cilostazol and pentoxifylline and has an estimated cost per quality-adjusted life year gained of around £6070 compared to no vasoactive drug. The analysis uses effectiveness evidence from a network meta-analysis. In contrast to previous guidelines recommending cilostazol, the analysis suggests that Naftidrofuryl oxalate is the only vasoactive drug for PAD which is likely to be cost-effective.
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systematic review of the efficacy of cilostazol Naftidrofuryl oxalate and pentoxifylline for the treatment of intermittent claudication
British Journal of Surgery, 2012Co-Authors: John Stevens, Hazel Squires, Emma Simpson, Yang Meng, S Harnan, J A Michaels, Steven M Thomas, Gerard StansbyAbstract:Background: A systematic review and network meta-analysis was undertaken to consider the evidence for the efficacy and tolerability of placebo, cilostazol, Naftidrofuryl oxalate and pentoxifylline in patients with intermittent claudication due to peripheral arterial disease (PAD). Methods: MEDLINE, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings, BIOSIS, National Research Register and MetaRegister databases were searched. Eligible studies were randomized controlled trials (RCTs) and published systematic reviews of patients with intermittent claudication due to PAD and whose symptoms persisted despite a period of conservative management. Study selection was conducted by one reviewer with involvement from a clinician. Data were extracted by one reviewer with no blinding to authors or journal, and checked by a second reviewer. Outcome measures were maximum walking distance (MWD) and pain-free walking distance (PFWD). Results: The review identified 1876 citations; 26 RCTs met the inclusion criteria for the systematic review. Eleven trials provided data relevant for the meta-analysis. Naftidrofuryl oxalate was ranked first for both MWD and PFWD (probability of 0·947 and 0·987, respectively, of being the best treatment) followed by cilostazol and pentoxifylline. For Naftidrofuryl oxalate, cilostazol and pentoxifylline, MWD increased by 60 (95 per cent credible interval 20 to 114) per cent, 25 (11 to 40) per cent and 11 (−1 to 24) per cent respectively relative to placebo, and PFWD increased by 49, 13 and 9 per cent. Conclusion: Naftidrofuryl oxalate and cilostazol are both effective treatments for claudication; Naftidrofuryl oxalate is likely to be the most effective, with minimal serious adverse events. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
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a systematic review and economic evaluation of cilostazol Naftidrofuryl oxalate pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease
Health Technology Assessment, 2011Co-Authors: Hazel Squires, Emma Simpson, Yang Meng, S Harnan, John Stevens, Ruth Wong, S Thomas, J A Michaels, Gerard StansbyAbstract:BACKGROUND: Peripheral arterial disease (PAD) is a condition in which there is blockage or narrowing of the arteries that carry blood to the legs and arms. It is estimated to affect around 4.5% of people aged between 55 and 74 years within the UK. The most common symptom of PAD is intermittent claudication (IC), characterised by pain in the legs on walking that is relieved with rest. OBJECTIVE: To assess the effectiveness and cost-effectiveness of cilostazol, Naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no vasoactive drugs, for IC due to PAD in adults whose symptoms continue despite a period of conventional management. DATA SOURCE: Electronic bibliographic databases were searched during April to June 2010 (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings Citation Index, BIOSIS Previews). REVIEW METHODS: Effectiveness outcomes sought were maximal walking distance (MWD), pain-free walking distance (PFWD), ankle-brachial pressure index, cardiovascular events, mortality, adverse events (AEs) and health-related quality of life (HRQoL). A narrative synthesis was provided for all outcomes and a network meta-analysis was undertaken for the walking distance outcomes. A Markov model was developed to assess the relative cost-effectiveness of the interventions from a NHS perspective over a lifetime. The model has three states: vasoactive drug treatment, no vasoactive drug treatment and death. Each 1-week cycle, patients may continue with the drug, discontinue the drug or die. Regression analysis was undertaken to model the relationship between MWD and utility so that a cost per quality-adjusted life-year (QALY) outcome measure could be presented. Univariate and probabilistic sensitivity analyses were undertaken. All costs and outcomes were discounted at 3.5%. RESULTS: Twenty-six randomised controlled trials were identified that met the inclusion criteria for the clinical effectiveness review. There was evidence that walking distance outcomes were significantly improved by both cilostazol and Naftidrofuryl oxalate; the 95% credible intervals for the difference from placebo in the logarithm mean change MWD from baseline were 0.108 to 0.337 and 0.181 to 0.762, respectively. It was not possible to include inositol nicotinate within the meta-analysis of MWD and PFWD owing to the lack of 24-month data; however, the shorter-term data did not suggest a significant effect. AEs were minor for all drugs and included headaches and gastrointestinal difficulties. The incidence of serious adverse events (SAEs), including cardiovascular events and mortality, was not increased by the vasoactive drugs compared with placebo; however, most studies had a relatively short follow-up time to address this outcome. HRQoL data were limited. Two studies of limited quality were identified within the review of cost-effectiveness. The de novo model developed suggests that Naftidrofuryl oxalate dominates cilostazol and pentoxifylline and has a cost per QALY gained of around £6070 compared with no vasoactive drug. This result is reasonably robust to changes within the key model assumptions. Inositol nicotinate was not included within the main analysis owing to lack of data. However, it is unlikely to be considered to be cost-effective due to its high acquisition cost (£900 vs £100-500 per year for the other drugs). CONCLUSIONS: Naftidrofuryl oxalate and cilostazol both appear to be effective treatments for this patient population, with minimal SAEs. However, Naftidrofuryl oxalate is the only treatment that is likely to be considered cost-effective. The long-term effectiveness is uncertain and hence a trial comparing cilostazol, Naftidrofuryl oxalate and placebo beyond 24 weeks would be beneficial. Outcomes associated with Naftidrofuryl oxalate could also be compared with those associated with supervised exercise programmes and angioplasty.
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a systematic review and economic evaluation of cilostazol Naftidrofuryl oxalate pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease
Health Technology Assessment, 2011Co-Authors: Hazel Squires, Emma Simpson, Yang Meng, S Harnan, John Stevens, Ruth Wong, S Thomas, J A Michaels, Gerard StansbyAbstract:Background Peripheral arterial disease (PAD) is a condition in which there is blockage or narrowing of the arteries that carry blood to the legs and arms. It is estimated to affect around 4.5% of people aged between 55 and 74 years within the UK. The most common symptom of PAD is intermittent claudication (IC), characterised by pain in the legs on walking that is relieved with rest. Objective To assess the effectiveness and cost-effectiveness of cilostazol, Naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no vasoactive drugs, for IC due to PAD in adults whose symptoms continue despite a period of conventional management. Data source Electronic bibliographic databases were searched during April to June 2010 (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings Citation Index, BIOSIS Previews). Review methods Effectiveness outcomes sought were maximal walking distance (MWD), pain-free walking distance (PFWD), ankle–brachial pressure index, cardiovascular events, mortality, adverse events (AEs) and health-related quality of life (HRQoL). A narrative synthesis was provided for all outcomes and a network meta-analysis was undertaken for the walking distance outcomes. A Markov model was developed to assess the relative cost-effectiveness of the interventions from a NHS perspective over a lifetime. The model has three states: vasoactive drug treatment, no vasoactive drug treatment and death. Each 1-week cycle, patients may continue with the drug, discontinue the drug or die. Regression analysis was undertaken to model the relationship between MWD and utility so that a cost per quality-adjusted life-year (QALY) outcome measure could be presented. Univariate and probabilistic sensitivity analyses were undertaken. All costs and outcomes were discounted at 3.5%. Results Twenty-six randomised controlled trials were identified that met the inclusion criteria for the clinical effectiveness review. There was evidence that walking distance outcomes were significantly improved by both cilostazol and Naftidrofuryl oxalate; the 95% credible intervals for the difference from placebo in the logarithm mean change MWD from baseline were 0.108 to 0.337 and 0.181 to 0.762, respectively. It was not possible to include inositol nicotinate within the meta-analysis of MWD and PFWD owing to the lack of 24-month data; however, the shorter-term data did not suggest a significant effect. AEs were minor for all drugs and included headaches and gastrointestinal difficulties. The incidence of serious adverse events (SAEs), including cardiovascular events and mortality, was not increased by the vasoactive drugs compared with placebo; however, most studies had a relatively short follow-up time to address this outcome. HRQoL data were limited. Two studies of limited quality were identified within the review of cost-effectiveness. The de novo model developed suggests that Naftidrofuryl oxalate dominates cilostazol and pentoxifylline and has a cost per QALY gained of around £6070 compared with no vasoactive drug. This result is reasonably robust to changes within the key model assumptions. Inositol nicotinate was not included within the main analysis owing to lack of data. However, it is unlikely to be considered to be cost-effective due to its high acquisition cost (£900 vs £100–500 per year for the other drugs). Conclusions Naftidrofuryl oxalate and cilostazol both appear to be effective treatments for this patient population, with minimal SAEs. However, Naftidrofuryl oxalate is the only treatment that is likely to be considered cost-effective. The long-term effectiveness is uncertain and hence a trial comparing cilostazol, Naftidrofuryl oxalate and placebo beyond 24 weeks would be beneficial. Outcomes associated with Naftidrofuryl oxalate could also be compared with those associated with supervised exercise programmes and angioplasty. Source of funding The National Institute for Health Research Health Technology Assessment programme.
