beraprost and Intermittent-Claudication

To evaluate the efficacy and safety of cilostazol, pentoxifylline, beraprost for intermittent claudication due to lower extremity arterial occlusive disease.. Randomized controlled clinical trials were identified from PubMed, Scopus, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, Wanfang and Chongqing VIP databases, from the database inception to 31/12/2021. The outcome measures were walking distance measured by treadmill (maximum and pain-free walking distance), ankle-brachial index and adverse events. The quality of included studies was assessed by the Cochrane bias risk assessment tool. A network meta-analysis was carried out with Stata 16.0 software.. There were 29 RCTs included in the study, covering total 5352 patients. Cilostazol was ranked first for both maximum and pain-free walking distance, followed by beraprost and pentoxifylline. For cilostazol, pentoxifylline and beraprost, maximum walking distance increased by 62.93 95%CI(44.06, 81.79), 32.72 95%CI(13.51, 55.79) and 43.90 95%CI(2.10, 85.71) meters, respectively relative to placebo, and pain-free walking distance increased by 23.92 95%CI(11.24, 36.61), 15.16 95%CI(2.33, 27.99) and 19.78 95%CI(-3.07, 42.62) meters. For cilostazol, pentoxifylline, beraprost and cilostazol combined with beraprost, ankle-brachial index increased by 0.06 95%CI(0.04, 0.07), -0.01 95%CI(-0.08, 0.05), 0.18 95%CI(0.12, 0.23) and 0.23 95%CI(0.18, 0.27), respectively relative to placebo. The pentoxifylline and cilostazol was associated with a lower ratio of adverse events than beraprost and cilostazol combined with beraprost.. Cilostazol, pentoxifylline and beraprost were all effective treatments for intermittent claudication; cilostazol with good tolerance was likely to be the most effective in walking distance, while beraprost and cilostazol combined with beraprost were more prominent in the ankle-brachial index.

Topics: Cilostazol; Humans; Intermittent Claudication; Network Meta-Analysis; Pentoxifylline; Randomized Controlled Trials as Topic; Vasodilator Agents

Peripheral arterial disease (PAD) is a common cause of morbidity in the general population. While numerous studies have established the efficacy of prostanoids in PAD stages III and IV, the question of the role of prostanoids as an alternative or additive treatment in patients suffering from intermittent claudication (PAD II) has not yet been clearly answered. This is an update of a Cochrane Review first published in 2004.. To determine the effects of prostanoids in patients with intermittent claudication (IC) Fontaine stage II.. For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). Clinical trials databases were searched for details of ongoing or unpublished studies. In addition, reference lists of relevant articles were checked.. Randomised clinical trials of prostanoids versus placebo or alternative ('control') treatment in people with intermittent claudication were considered for inclusion.. Two authors independently assessed trial quality and extracted data. Primary outcomes included pain-free walking distance (PFWD) and maximum walking distance (MWD), presented as mean change in walking distance during the course of the trial (% improvement) and as final walking distance (that is walking distance, in metres, after treatment) for the prostanoid and control groups.. Eighteen trials with a total of 2773 patients were included (16 in the original review and a further two in this update). As the majority of trials did not report standard deviations for the primary PFWD and MWD outcomes, it was often not possible to test for the statistical significance of any improvements in walking distance between groups. The quality of individual trials was variable and usually unclear due to insufficient reporting information. Comparison between trials was hampered by the use of different treadmill testing protocols, including different walking speeds and gradients. Such limitations in the data and the trial heterogeneity meant it was not possible to meaningfully pool results by meta-analysis.Four trials compared prostaglandin E1 (PGE1) with placebo; individual trials showed significant increases in walking distances with administration of PGE1 and in several trials the walking capacity remained increased after termination of treatment. Compared with pentoxifylline, PGE1 was associated with a higher final PFWD and MWD but these results were based on final walking distances rather than changes in walking distance from baseline. When PGE1 was compared with other treatments including laevadosin, naftidrofuryl and L-arginine, improvements in walking distances over time were observed for both PGE1 and the alternative treatment, but it was not possible from the data available to analyse statistically whether or not one treatment was more effective than the other.Six studies compared various preparations of prostacyclins (PGI2) with placebo. In one study using three different dosages of iloprost, PFWD and MWD appeared to increase in a dose-dependent manner; iloprost was associated with headache, pain, nausea and diarrhoea, leading to a higher rate of treatment withdrawal. Of three studies using beraprost sodium, one showed an improvement in PFWD and MWD compared with placebo while two showed no significant benefit. Beraprost sodium was associated with an increased incidence of drug-related adverse events. Of two studies on taprostene, the results of one in particular must be interpreted with caution due to an imbalance in walking capacity at baseline.Comprehensive, high quality data on outcomes such as quality of life, ankle brachial index, venous occlusion plethysmography and haemorrheological parameters were lacking.. Whilst results from some individual studies suggested a beneficial effect of PGE1, the quality of these studies and of the overall evidence available is insufficient to determine whether or not patients with intermittent claudication derive clinically meaningful benefit from the administration of prostanoids. Further well-conducted randomised, double blinded trials with a sufficient number of participants to provide statistical power are required to answer this question.

Topics: Alprostadil; Epoprostenol; Humans; Iloprost; Intermittent Claudication; Prostaglandins; Randomized Controlled Trials as Topic

To study the effectiveness for the treatment of intermittent claudication (IC) of three drugs with antiplatelet effects, cilostazol, beraprost sodium, and prostaglandin E(1) (PGE(1)), by using a systemic review of literature and a meta-analysis. A search was undertaken for studies reported between 1966-2002 in the MEDLINE database, and references in published articles and reviews were obtained. Data for maximum walking distance (MWD), pain-free walking distance (PFWD), and adverse clinical events were extracted from the articles that met the inclusion criteria. The pooled estimates of the weighted mean differences (WMD) of MWD and PFWD for cilostazol were 52.19 m [95% confidence interval (CI) 32.08, 72.31] and 39.75 m [95% CI 23.39, 56.10], and those for PGE(1) were 100.27 m [95% CI 15.76, 184.78] and 55.73 [95% CI 21.54, 89.92], respectively. These differences were statistically significant between the test drugs and placebo. However there was no statistical significance difference between beraprost sodium and placebo, even though there was one study that showed a tendency for improvement in walking distance. The total rate of adverse clinical events in cilostazol and beraprost sodium was higher than that for placebo, while there was no statistical significant difference between PGE(1) and placebo, although PGE(1) had a higher tendency for adverse clinical events. The literature evaluation results and the meta-analysis suggest that these two drugs (cilostazol and PGE(1)) can be considered to be effective drugs for the treatment of IC. Due to current availability of only a few clinical reports, further studies are needed to clarify the efficacy of beraprost sodium in the treatment of IC.

Topics: Alprostadil; Cilostazol; Epoprostenol; Humans; Intermittent Claudication; Platelet Aggregation Inhibitors; Tetrazoles; Treatment Outcome; Walking

This study aimed to evaluate the effect of oral beraprost sodium, a prostaglandin I2 analogue, on symptoms of intermittent claudication in patients with arteriosclerosis obliterans. The research design consisted of a before and after treatment study without comparison groups. The subjects comprised arteriosclerosis obliterans patients who experienced intermittent claudication. Furthermore, this study aimed to assess the mechanism of action of beraprost sodium via blood sampling and measurements of flow-mediated vasodilatation before and after treatment.. The study was performed prospectively in 7 patients with arteriosclerosis obliterans. Beraprost sodium (40 microg) was orally administered to 7 patients at study entry, followed by administration of 120 microg/day for 12 weeks. Blood sampling and measurements of flow-mediated vasodilatation were performed before and after treatment at study entry, 4 weeks, and 12 weeks after treatment. Treadmill exercise tests were performed three times at study entry, 4 weeks, and 12 weeks after treatment. The ankle-brachial index (ABI) was measured at rest and after exercise.. Pain-free walking distances increased by 138% at 12 weeks after treatment. Maximum walking distances increased by 133%. The ABI was significantly increased at 4 weeks and 12 weeks after treatment at rest. Endothelin-1 levels tended to be decreased at 1 h after administration of 40 microg beraprost sodium. N(G),N(G)-dimethyl-L-arginine, nitrate ions, and flow-mediated vasodilatation.. Beraprost sodium tended to decrease endothelin-1 levels and improved symptoms of intermittent claudication in patients with arteriosclerosis obliterans.

Topics: Administration, Oral; Aged; Ankle Brachial Index; Arginine; Arteriosclerosis Obliterans; Biomarkers; Endothelin-1; Epoprostenol; Exercise Test; Exercise Tolerance; Humans; Intermittent Claudication; Platelet Aggregation Inhibitors; Prospective Studies; Time Factors; Treatment Outcome; Vasodilation; Vasodilator Agents; Walking

In the current study, we hypothesized that beraprost would: 1) improve treadmill exercise performance and quality of life; and 2) decrease rates of ischemic events in patients with intermittent claudication.. Previous trials with beraprost sodium, an orally active prostaglandin I(2) analogue, in the treatment of claudication in patients with peripheral arterial disease (PAD) have been inconsistent.. Patients with intermittent claudication (n = 897) were randomized to receive either 40 microg three times a day of beraprost with meals (n = 385) or placebo (n = 377) in a double-blinded manner for one year. The primary efficacy parameter was treadmill-measured maximum walking distance, as assessed at three and six months after randomization. Secondary efficacy parameters included treadmill-measured pain-free walking distance and change in quality of life.. There was no significant improvement in maximum walking distance in the beraprost group (16.7%) as compared with the placebo group (14.6%, p = NS). Administration of beraprost did not improve the pain-free walking distance (p = NS between treatment groups), and there was no improvement in the quality-of-life measures between the treatment groups. The incidence of critical cardiovascular events was 7.3% in the beraprost group and 11.4% in the placebo group (p = NS). There was a significant reduction in the combination of cardiovascular death and myocardial infarction in the beraprost group (p = 0.01).. Despite previous investigations suggesting efficacy, these results indicate that beraprost is not an effective treatment to improve symptoms of intermittent claudication in patients with PAD. The potential benefit of beraprost on critical cardiovascular events would require confirmation in a larger prospective investigation.

Topics: Administration, Oral; Aged; Double-Blind Method; Epoprostenol; Exercise Test; Exercise Tolerance; Female; Humans; Intermittent Claudication; Male; Middle Aged; Pain; Platelet Aggregation Inhibitors; Quality of Life; Vasodilator Agents; Walking

Beraprost sodium (BPS) is a new stable, orally active prostaglandin I(2) analogue with antiplatelet and vasodilating properties. We report the results of a phase III clinical trial of BPS in patients with intermittent claudication.. Patients (n=549) with a pain-free walking distance of between 50 and 300 m were entered into a 4-week single-blind placebo run-in phase. Patients whose pain-free walking distance had changed by <25% were then randomized to receive either BPS (40 microg TID, n=209) or placebo (n=213) in a double-blind manner for 6 months. Pain-free and maximum walking distances were measured on the occasion of treadmill exercise tests performed at baseline and 1.5, 3, 4.5, and 6 months after randomization. Success was defined as an improvement of >50% in pain-free walking distance at month 6 and in > or =1 earlier treadmill exercise test in the absence of critical cardiovascular events. Success was observed more frequently in the BPS group (43.5%) than in the placebo group (33.3%, P=0.036). Pain-free walking distances increased by 81.5% and 52.5%, respectively, in the BPS and placebo groups (P=0.001) and maximum walking distances by 60.1% and 35.0%, respectively (P=0.004). The incidence of critical cardiovascular events was 4.8% in the BPS group and 8.9% in the placebo group.. These results show that BPS is an effective symptomatic treatment of patients with intermittent claudication. The beneficial effects of BPS on critical cardiovascular events should be confirmed in appropriate clinical trials.

Topics: Administration, Oral; Adult; Aged; Double-Blind Method; Epoprostenol; Female; Humans; Intermittent Claudication; Male; Middle Aged; Treatment Outcome; Vasodilator Agents

We compared the efficacy and safety of three doses of beraprost sodium, an epoprostenol analogue, with placebo in the treatment of intermittent claudication (Fontaine's stage II). One hundred sixty-four patients were randomized to receive either placebo, 20 micrograms beraprost sodium (BPS60 group), 40 micrograms beraprost sodium (BPS120 group), or 60 micrograms beraprost sodium (BPS180 group) three times daily administered orally in a double-blind manner for 12 weeks. Treadmill exercise tests were performed twice during an initial selection phase (D-28 and D0) at week 10 (at trough beraprost concentration) and week 12 (at peak beraprost concentration) of the treatment phase. At week 10, all groups showed an increase in pain-free walking distance, and this distance was greatest in the BPS60 and BPS120 groups (p = 0.055). At week 12, a similar pattern was observed, and the difference was significant between the groups (p = 0.023). The most frequent adverse events reported were gastrointestinal disorders, headaches, skin disorders, and flushes. Patients who received either 60 or 120 micrograms of beraprost sodium daily had an increased pain-free walking distance. Further studies are required to investigate why the highest dose used (180 micrograms daily) showed lower efficacy. Having both vasodilating and antiplatelet properties and being able to increase pain-free walking distance in the short term, beraprost sodium is a promising drug for the treatment of intermittent claudication.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Epoprostenol; Exercise Test; Female; Gastrointestinal Diseases; Headache; Humans; Intermittent Claudication; Middle Aged; Platelet Aggregation Inhibitors; Vasodilator Agents

Arteriosclerosis obliterans (ASO) causes ischemic symptoms of the lower limbs, reducing quality of life (QOL), and has a poor prognosis. Early diagnosis and treatment are necessary. In this study, the effects of long-term administration of beraprost sodium (beraprost) to treat ASO were investigated.. One hundred and eighty eight patients treated with beraprost for ≥1 year were retrospectively identified. Outcomes were lower limb ischemic symptoms, carotid intima/media thickness (IMT), and cardiovascular events. Patients reported visual analog scale scores for major symptoms at baseline and after 3, 6, and 12 months of treatment.. Overall, 188 patients (mean age 70.8 ± 10.15 years, Fontaine classification: grade I 14.4%, grade II 85.6%) treated with beraprost for 2.4-10.7 years (mean 6.5 years) were included in this study. Administration of beraprost significantly reduced patient-reported severity of lower limb ischemic symptoms in all patients at 12 months, including those with diabetes, hypertension, or dyslipidemia. IMT decreased from 1.09 ± 0.09 mm at baseline to 1.04 ± 0.11 mm at 12 months (P < 0.001). Decreases in IMT were similar in patients with diabetes, hypertension, or dyslipidemia. Overall, 26 (13.8%) events occurred during a mean follow-up of 6.5 years, including 23 cardiovascular events (unstable angina in three patients, myocardial infarction in six patients, cerebral infarction in eight patients, and transient cerebral ischemic attack in six patients) and non-cardiovascular death in three patients. Beraprost at 120 μg/day significantly reduced the risk of ischemic symptoms compared with <120 μg/day (adjusted hazard ratio: 0.17; 95% confidence interval: 0.06, 0.45; P < 0.001). No severe adverse events or adverse events requiring dose reductions/discontinuation occurred during long-term administration of beraprost.. Beraprost reduced lower limb ischemic symptoms, IMT, and the incidence of cardiovascular events in patients with ASO.

Topics: Aged; Aged, 80 and over; Arteriosclerosis Obliterans; Carotid Intima-Media Thickness; Epoprostenol; Female; Humans; Intermittent Claudication; Japan; Male; Middle Aged; Quality of Life; Retrospective Studies; Treatment Outcome; Vasodilator Agents

In rats receiving bilateral femoral arteries ligation (day 0), repeated oral administration of the prostacyclin derivative beraprost sodium (50 microg/kg, b.i.d.) from day 1 to day 5 resulted in a significant prolongation in walking time in rotarod walking exercise performed on day 5. Similarly, results were obtained in rats with bilateral femoral arterial thrombosis induced by application of FeCl(3)/HCl. In the ligation model, a significant increase was observed in femoral/carotid arterial blood pressure ratio even on day 2. These results indicated that beraprost sodium improves blood flow and walking disturbances associated with arterial occlusion in rats.

Topics: Animals; Arterial Occlusive Diseases; Epoprostenol; Femoral Artery; Intermittent Claudication; Male; Rats; Rats, Wistar; Regional Blood Flow; Walking

Topics: Administration, Oral; Epoprostenol; Humans; Intermittent Claudication; Platelet Aggregation Inhibitors; Vasodilator Agents

The syndrome of intermittent claudication can be induced not only by vascular insufficiency of the lower limbs but also by diseases of the spinal cord and cauda equina. The authors describe a sixty-year-old man with intermittent claudication due to spinal canal stenosis who was successfully treated with beraprost sodium, a stable prostaglandin I2 analogue. This drug has a long biological half-life and is orally effective in vasodilation, which is suggested to be beneficial in treating this syndrome. Beraprost sodium may become one of the major drugs for conservative therapy of intermittent claudication induced by spinal canal stenosis.

Topics: Epoprostenol; Humans; Intermittent Claudication; Magnetic Resonance Imaging; Male; Middle Aged; Radiography; Spinal Stenosis; Vasodilator Agents

The effects of medical treatment with a prostaglandin I2 analog (beraprost sodium) were evaluated in 19 of 120 cases studied with near-infrared spectroscopy (NIRS) from January 1993 to September 1994. The relative changes in oxygenated (Oxy) and deoxygenated (Deo) hemoglobin (Hb) in the calf muscle were measured during a treadmill walking test and the subsequent recovery period. After medical treatment in these 19 cases, recovery time of OxyHb decreased in 10 cases, increased in 7 cases and remained unchanged in two cases. Pressure studies did not facilitate the assessment of changes in the severity of claudication. Our results demonstrate that NIRS can provide objective information regarding the effects of medical therapy in claudicants.

Topics: Aged; Aged, 80 and over; Epoprostenol; Exercise Test; Humans; Intermittent Claudication; Male; Middle Aged; Muscles; Oxygen; Oxyhemoglobins; Platelet Aggregation Inhibitors; Spectrophotometry, Infrared