iloprost and Intermittent-Claudication

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 Clinical trials databases were searched for details of ongoing or unpublished studies.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

Patients with critical limb ischemia (CLI) have low levels of endothelial progenitor cells (EPC). Iloprost has been demonstrated to stimulate vascular endothelial growth factor (VEGF) and promote angiogenesis. We investigated the effects of iloprost on EPC levels in vivo in CLI patients. Twenty-three patients with stage III and IV CLI were treated with iloprost for four weeks, improving clinical and instrumental parameters. Mononuclear cells isolated from peripheral blood were cultured to obtain "early" EPC, evaluated counting adherent cells with double positivity for acetylated low-density lipoprotein uptake and Ulex Europaeus lectin at flow cytometry. These cells also co-expressed the monocyte markers CD14 and CD45. Iloprost increased EPC number in the whole patient population: pre-treatment median: 13,812/ml; range: 1,263-83,648/ml; post-treatment median: 23,739/ml; range: 3,385-99,251/ml; p = 0.035, irrespective of age, sex, disease stage or atherosclerosis risk factors. In conclusion, iloprost increases EPC number in peripheral blood in vivo. Such an effect may have therapeutic relevance.

Topics: Aged; Aged, 80 and over; Angiogenesis Inducing Agents; Carbon Dioxide; Cells, Cultured; Critical Illness; Endothelial Cells; Extremities; Female; Humans; Iloprost; Infusions, Intravenous; Intermittent Claudication; Ischemia; Male; Oxygen; Stem Cells; Treatment Outcome; Vascular Endothelial Growth Factor A

Prostanoids, which promote vasodilation and reduce platelet aggregation, have been proposed as candidate therapies for intermittent claudication due to peripheral arterial disease (PAD). However, studies of these medications have yielded inconsistent results. This study tested the hypothesis that iloprost, an oral prostacyclin analogue, would improve walking distance and quality of life in patients with intermittent claudication. The study was a multi-center, randomized, double-blind, placebo-controlled trial comparing three doses of oral iloprost (50 microg, 100 microg, or 150 microg twice daily), pentoxifylline, or placebo in 430 patients with intermittent claudication. The primary outcome measure was improvement in absolute claudication distance (ACD) after 6 months. Secondary outcomes included initial claudication distance and quality of life assessment. Placebo increased ACD by 3.3%, and iloprost increased peak ACD by 7.7%, 8.8% and 11.2% at the 50 microg, 100 microg, and 150 microg twice-daily doses, respectively (all insignificant relative to placebo). Pentoxifylline increased ACD by 13.9% relative to placebo (p = 0.039). Neither iloprost nor pentoxifylline enhanced quality of life. These results indicate that oral iloprost is not effective in improving exercise performance or quality of life in patients with PAD who have intermittent claudication.

Topics: Administration, Oral; Aged; Double-Blind Method; Female; Humans; Iloprost; Intermittent Claudication; Male; Pentoxifylline; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Prospective Studies; Quality of Life; Recovery of Function; Treatment Failure; United States; Vasodilator Agents; Walking

Eicosanoids with vasodilating and angiogenic properties have been postulated to be effective therapies for critical leg ischemia (CLI) secondary to atherosclerotic peripheral arterial disease. The ability to deliver active drug to the site of action at adequate doses for sufficient duration has been a major limitation in the clinical development of such therapies. Lipo-ecraprost is a lipid-encapsulated prostaglandin E1 prodrug with the potential to deliver active prostaglandin to the site of critical arterial ischemia. The current trial was designed to test the hypothesis that lipo-ecraprost would improve amputation-free survival in patients with CLI who had no revascularization options.. The study was randomized, multicenter, double blind, and placebo controlled. Patients who met clinical and hemodynamic criteria were randomized to receive placebo or lipo-ecraprost (60 microg) administered intravenously on each of 5 days per week, for a total of 8 weeks. The study's primary endpoint was the rate of a composite end point of death or amputation above the level of the ankle at 180 days (6 months).. The study was terminated on a recommendation from the Data and Safety Monitoring Board after the completion of a protocol-specified interim analysis for futility. At the time of termination, 383 of the planned 560 patients had been randomized, of which 379 received at least one dose of study medication and thus were included in the intention-to-treat population. Twenty-three patients were lost to follow-up and were not available for 6-month assessments. At 6 months of follow-up, there were 23 amputations in the 177 patients who received placebo, and 29 amputations in the 179 patients randomized to lipo-ecraprost. At 6 months, 10 deaths had occurred in the placebo group and 18 deaths had occurred in the lipo-ecraprost arm. Changes in lower-extremity hemodynamics over the 6-month study period did not differ between the placebo and lipo-ecraprost treatment arms.. Intensive treatment with lipo-ecraprost failed to modify the 6-month amputation rate in patients with CLI who were not candidates for revascularization.

Topics: Adult; Aged; Aged, 80 and over; Alprostadil; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Carriers; Female; Follow-Up Studies; Humans; Iloprost; Infusions, Intravenous; Intermittent Claudication; Ischemia; Leg; Limb Salvage; Lipids; Male; Middle Aged; Pain Measurement; Peripheral Vascular Diseases; Reference Values; Risk Assessment; Treatment Outcome; Ultrasonography

In peripheral vascular disease (PVD), impaired blood viscosity (BV) plays a major role in residual microvascular perfusion. Indeed, during acute leg ischaemia factors influencing microvascular BV include the plasma fibrinogen concentration, red and white blood cell rheology, as well as platelet aggregation and activation.. To assess the effects of Iloprost in patients with PVD.. The effects of an infusion of a single dose of Iloprost (from 0.5 up to a maximum of 2 ng/kg/min. over 6 hours) in 16 patients with stage II peripheral vascular disease on blood rheology and tissue perfusion were determined in a double-blind placebo-controlled study, using repeated treadmill exercise test to stress leg circulation. Blood viscosity at low shear, soluble P-selectin levels (expression of platelet activation), unfractionated leukocyte and erythrocyte filterability rates, plasma fibrinogen concentration, haematocrit, leukocyte and platelet counts and transcutaneous oxygen pressure (TcPO(2)) were measured in two matched groups of 8 PVD patients before and after Iloprost infusion.. Controlled peripheral ischaemia generated an impaired haemorheological profile; Iloprost reduced the impairments in BV and the filterability rates of unfractionated leukocytes and erythrocytes, inhibited platelet activation, and improved erythrocyte deformability. These changes were associated with significant shortening of the TcPO(2) half recovery time (the drop of TcPO(2) occurs because the ischaemic skeletal muscle steals oxygen from the skin), indicating that ischaemic damage had been contained.. Our results show that the infusion of a single dose of Iloprost in patients with PVD is associated with a significant improvement in microvascular functioning

Topics: Blood Viscosity; Double-Blind Method; Exercise Test; Hemorheology; Humans; Iloprost; Intermittent Claudication; Male; Microcirculation; Middle Aged; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Treatment Outcome; Vasodilator Agents

24 hour infusion of iloprost was compared with placebo infusion in 19 patients with stable intermittent claudication using a double blind, balanced crossover design. Despite significant inhibition of platelet aggregation to ADP and collagen (p less than 0.001) and the typical cardiovascular and gastrointestinal side effects, there was no significant effect on treadmill exercise times at any time up to 6 weeks after infusion. The 95% confidence limits indicated that an improvement of more than 25% was unlikely to occur. No significant changes in B thromboglobulin, platelet aggregate ratio, bleeding time, whole blood viscosity and euglobulin clot lysis time were demonstrated.

Topics: Aged; Blood Coagulation; Clinical Trials as Topic; Double-Blind Method; Epoprostenol; Fibrinolysis; Humans; Iloprost; In Vitro Techniques; Infusions, Parenteral; Intermittent Claudication; Male; Middle Aged; Platelet Aggregation; Vasodilation

In a randomized patient-blind study iloprost or hydroxy-ethyl starch 200/0.5 were given i.v. 5 h daily for 2 weeks to 24 patients suffering from severe intermittent claudication due to peripheral vascular disease. An increase in pain-free walking distance of more than 50% occurred in 6 of 11 patients after the iloprost infusions and in 7 of 12 patients after HES treatment. No significant effects on haemodynamic or clinical chemistry tests were observed.

Topics: Aged; Anti-Arrhythmia Agents; Arterial Occlusive Diseases; Blood Viscosity; Epoprostenol; Erythrocyte Aggregation; Humans; Iloprost; Infusions, Intravenous; Intermittent Claudication; Male; Middle Aged; Physical Exertion; Plethysmography

Peripheral vascular occlusive disease (PAOD) is frequently seen in patients suffering from coronary heart or cerebrovascular disease and is, considered as a prognostic predictor for the morbidity and mortality of this patient group. Thus, secondary antithrombotic and antiplatelet prophylaxis in these patients is not limited to achievement of long-term patency of the revascularized or recanalized arterial segment, but plays as well a pivotal role for the prevention of myocardial infarction and stroke. Generally, claudicants as well as patients undergoing percutaneous transluminal angioplasty (PTA), supragenicular femoro-popliteal artificial bypass surgery, aortofemoral, iliaco-femoral unilateral bypass, or aortobifemoral Y-graft implantation with unimpaired arterial outflow are treated life-long with low dose acetylsalicylic acid (ASA) 75-250 mg. On the other hand, those undergoing axillo-femoral, femoro-femoral crossover, aorto-profundal or femoro-popliteal infragenicular and femoro-distal venous bypass surgery should be treated with vitamin K antagonists. The role of Clopidogrel in secondary prevention after peripheral revascularization and recanalization still needs to be defined.

Topics: Administration, Oral; Angioplasty, Balloon; Anticoagulants; Arterial Occlusive Diseases; Aspirin; Blood Vessel Prosthesis; Clopidogrel; Confidence Intervals; Dipyridamole; Drug Therapy, Combination; Embolectomy; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Iloprost; Intermittent Claudication; Leg; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Thrombectomy; Ticlopidine; Time Factors; Vitamin K

Topics: Alprostadil; Arterial Occlusive Diseases; Controlled Clinical Trials as Topic; Extremities; Fibrinolytic Agents; Humans; Iloprost; Intermittent Claudication; Ischemia; Meta-Analysis as Topic; Microcirculation; Multivariate Analysis; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Prognosis; Retrospective Studies; Vasodilator Agents; Walking

The aim of this retrospective, study was to assess the tolerance and therapeutic effect of a stable prostacyclin (iloprost) analog in severe forms of permanent lower limb ischemia. Ninety consecutive unselected patients, in Leriche and Fontaine stages III or IV, turned down for vascular surgery after angiography and treated with iloprost for 28 days were enrolled in the study. Patients were followed up clinically (ischemic pain, trophic changes, walking distance) and with transcutaneous oxymetry (D28). Long-term assessment (mean 2 years) was expressed as rates of death, major amputation and "patients alive with limb". There were no manifestations of intolerance to iloprost. At two months, 42 out of 90 patients (47%) were considered as responders because of a lack (n=36) or significant decrease (n=6) in pain, reduction of trophic lesions and conservative walking. At long term (6 months, one and two years) we observed that 10 (11%), 17 (20%) and 22 (25%) patients respectively had died, 24 (27%), 26 (30%) and 28 (32%) patients underwent major amputation, but 60 (68%), 54 (62%) and 49 (56%) patients still alive with their limb and conservative walking. No predictive factors were noted, but diabetic patients without microangiopathy or recent bypass occlusions (respectively 43% and 56% out of patients were alive with limb at 6 months) were associated with bad results. This retrospective study, despite its limitations, underlines the good tolerance to, and effectiveness of iloprost in non surgical chronic critical ischemia. However, no predictive criterion of long-term effectiveness could be established, except initial clinical severity and clinical change one month after treatment.

Topics: Adult; Aged; Aged, 80 and over; Arteriosclerosis Obliterans; Female; Humans; Iloprost; Intermittent Claudication; Ischemia; Leg; Male; Middle Aged; Retrospective Studies; Vasodilator Agents

Treatment of arteriopathy of the lower limbs (ALL) with vasoactive drugs must follow French health laws recently introduced in regard to the prescription of unuseful drugs and treatments and the frequency at which some patients resort to specific drugs and treatments. Prescription of vasoactive drugs in ALL requires the existence of functional discomfort. Prescription of only one vasoactive drug is sufficient.. Results of published clinical trials demonstrate the efficacy of vasoactive drugs for the relief of claudication related to arteriopathy. To conform to the rules of the European Drug Agency, treatment with vasoactive drugs which improve the walking distance is recommended as "symptomatic treatment of arterial claudication in ALL". Iloprost is only used in the treatment of permanent ischemia. Prescription of vasoactive drugs is part of a scheme of therapeutic indications that are well known and rigorous. Rules of hygiene and reduction of risk factors are the essential preliminary elements. In the case of arterial claudication due to femoral or distal obliteration, chemical medication is suggested, whereas in the case of iliac lesion, angioplasty should be considered.. Walking is recommended in all the cases; however, usually less than a quarter of all patients will conform to this recommendation. Vasoactive drugs thus find their place in the therapeutic scheme. Evaluation of the efficiency of vasoactive drugs rises above simple measures of the walking distance, rather integrating quality of life and usefulness of the treatment.

Topics: Angioplasty; Arterial Occlusive Diseases; Contraindications; Drug Prescriptions; Drug Utilization; Femoral Artery; France; Humans; Iliac Artery; Iloprost; Intermittent Claudication; Ischemia; Leg; Legislation, Drug; Quality of Life; Vasodilator Agents; Walking

Topics: Arterial Occlusive Diseases; Hemodynamics; Humans; Iloprost; Intermittent Claudication; Vasodilator Agents

Cholesterol embolisation is a little known complication of aortic surgery and radiological procedures with a mortality of 81%. Treatment has been poorly described and inadequate. We report a case in which we have followed an aggressive policy of treatment using modern vascular techniques not previously described in this condition.

Topics: Angiography; Aorta, Abdominal; Arteriovenous Fistula; Blood Vessel Prosthesis; Cholesterol; Combined Modality Therapy; Drug Therapy, Combination; Embolism; Femoral Artery; Humans; Iloprost; Injections, Intra-Arterial; Intermittent Claudication; Ischemia; Leg; Male; Middle Aged; Postoperative Complications; Pulse; Reoperation; Streptokinase

The efficacy, tolerance and safety of iloprost, a stable analogue of carbaprostacyclin, were evaluated in 7 patients with peripheral arterial insufficiency at stage II of Fontaine's classification. After washout, placebo was infused intravenously for seven days, then iloprost was given by a six-hour intravenous infusion of 1 ng/kg/min over the next seven days. At the end of each period, the initial (ICD) and the absolute (ACD) claudication distance were measured by treadmill. The ankle/arm systolic blood pressure ratio (WI) was also assessed, at rest and ten minutes after exercise. As compared with placebo, ICD increased from 98 +/- 60 to 137 +/- 91 meters (p less than 0.05) and ACD from 151 +/- 76 to 210 +/- 95 meters (p less than 0.05). Similarly, WI rose from 0.44 +/- 0.14 to 0.52 +/- 0.18 (p less than 0.05) at rest and from 0.40 +/- 0.13 to 0.48 +/- 0.20 (p less than 0.05) ten minutes after treadmill exercise. Owing to the spontaneous fluctuation in walking distance experienced by such patients, an increase in ACD greater than or equal to 50% was considered as clinically relevant. In 3 patients, who experienced such an improvement, iloprost continued to be infused at the same dosage as before, for an additional seven days. In the remaining 4 patients (nonresponders), the dose was increased to 2 ng/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Pressure; Epoprostenol; Exercise; Female; Heart Rate; Humans; Iloprost; Infusions, Intravenous; Intermittent Claudication; Male; Middle Aged; Platelet Aggregation Inhibitors