iloprost and Peripheral-Arterial-Disease

Peripheral arterial disease (PAD) is a common circulatory problem that can lead to reduced blood flow to the limbs, which may result in critical limb ischaemia (CLI), a painful manifestation that occurs when a person is at rest. The mainstay of treatment for CLI is surgical or endovascular repair. However, when these means of treatment are not suitable, due to anatomical reasons or comorbidities, treatment for pain is limited. Lumbar sympathectomy and prostanoids have both been shown to reduce pain from CLI in people who suffer from non-reconstructable PAD, but there is currently insufficient evidence to determine if one treatment is superior. Due to the severity of the rest pain caused by CLI, and its impact on quality of life, it is important that people are receiving the best pain relief treatment available, therefore interest in this area of research is high.. To compare the efficacy of lumbar sympathectomy with prostanoid infusion in improving symptoms and function and avoiding amputation in people with critical limb ischaemia (CLI) due to non-reconstructable peripheral arterial disease (PAD).. The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 29 March 2017) and CENTRAL (2017, Issue 2). The CIS also searched clinical trials databases for ongoing or unpublished studies.. Randomised controlled trials (RCTs), with parallel treatment groups, that compared lumbar sympathectomy (surgical or chemical) with prostanoids (any type and dosage) in people with CLI due to non-reconstructable PAD.. Three review authors independently selected trials, extracted data and assessed risk of bias. Any disagreements were resolved by discussion. We performed fixed-effect model meta-analyses, when there was no overt sign of heterogeneity, with risk ratios (RRs) and 95% confidence intervals (CIs). We graded the quality of evidence according to GRADE.. We included a single study in this review comparing lumbar sympathectomy with prostanoids for the treatment of CLI in people with non-reconstructable PAD. The single study included 200 participants with Buerger's disease, a form of PAD, 100 in each treatment group, but only 162 were actually included in the analyses. The study compared an open surgical technique for lumbar sympathectomy with the prostanoid, iloprost, and followed participants for 24 weeks.Risk of bias was low for most evaluated domains. Due to the nature of the treatment, blinding of the participants and those providing the treatment would be impossible as a surgical procedure was compared with intravenous injections. It was not mentioned if blinded assessors evaluated the study outcomes, therefore, we judged subjective outcomes (i.e. pain reduction) to be at unclear risk of detection bias and objective outcomes (i.e. ulcer healing, amputation and mortality) at low risk of detection bias. We also rated the risk of attrition bias as unclear; 38 out of 200 (19%) participants were not included in the analysis without clear explanation (16 of 100 in the iloprost arm and 22 of 100 in the sympathectomy arm). The quality of evidence was low due to serious imprecision because the study numbers were low and there was only one study included.The single included study reported on the outcome of complete healing without pain or major amputation, which fell under three separate outcomes for our review: relief of rest pain, complete ulcer healing and avoidance of major amputation. We chose to keep the outcome as a singularly reported outcome in order to not introduce bias into the outcomes, which may have been the case if reported separately. The limited evidence suggests participants who received prostaglandins had improved complete ulcer healing without rest pain or major amputation when compared with those who received lumbar sympathectomy (RR 1.63, 95% CI 1.30 to 2.05), but as it was the only included study, we rated the data as low-quality and could not draw any overall conclusions. The study authors stated that more participants who received prostaglandins reported adverse effects, such as headache, flushing, nausea and abdominal discomfort, but only one participant experienced severe enough adverse effects to drop out. Five participants who underwent lumbar sympathectomy reported minor wound infection (low-quality evidence). There was no reported mortality in either of the treatment groups (low-. Low-quality evidence from a single study in a select group of participants (people with Buerger's disease) suggests that prostaglandins are superior to open surgical lumbar sympathectomy for complete ulcer healing without rest pain or major amputation, but possibly incur more adverse effects. Further studies are needed to better understand if prostaglandins truly are more efficacious than open surgical lumbar sympathectomy and if there are any concerns with adverse effects. It would be of great importance for future studies to include other forms of PAD (as Buerger's disease is a select type of PAD), other methods of sympathectomy as well as data on quality of life, complications and cost-effectiveness.

Topics: Humans; Iloprost; Ischemia; Leg Ulcer; Pain Management; Peripheral Arterial Disease; Prostaglandins; Sympathectomy; Thromboangiitis Obliterans; Vasodilator Agents

Diabetic complications in the lower extremities, especially those secondary to diabetic macroangiopathy, have increasingly become a clinical emergency, given the high prevalence and progression of the disease. Until recently, the only approach to treating advanced stage disease was medical therapy and major amputation; however, the advent of revascularization procedures has radically improved the prognosis of patients with critical lower limb ischemia. In this setting, iloprost holds a dual position: as first-choice therapy in patients ineligible for revascularization and as complementary therapy in candidates for surgical or endovascular revascularization.

Topics: Diabetic Angiopathies; Drug Interactions; Humans; Iloprost; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prostaglandins

Aim This pilot study aimed to reveal whether combination of electrostimulation with iloprost treatment achieves better results compared to iloprost alone in patients with critical limb ischemia. Material and methods Patients were randomized into Group 1 ( n = 11, mean age: 65.3 ± 4.2 years, received iloprost infusion protocol alone) or Group 2 ( n = 11, mean age: 62.9 ± 6.7, received iloprost infusion plus standardized protocol of peroneal nerve electrostimulation). Electrostimulation was delivered with 1 Hz frequency, 27 mA current, and 200 ms pulse width. Peak blood flow velocities in the anterior and posterior tibialis arteries were measured with duplex ultrasound. Results There was a slight insignificant increase in blood velocity in anterior tibialis artery in Group 1 (from 17.6 ± 13.0 to 18.6 ± 13.1, p = 0.57), whereas the increase in Group 2 was marked (from 23.8 ± 18.3 to 32.2 ± 19.7, p = 0.01). Blood velocity in posterior tibialis artery also increased in both groups, but it was not of statistical significance. No significant difference was found between two groups in regard to final pulse oximetry oxygen saturation levels. Conclusion Electrostimulation of the peroneal nerve caused a substantial increase in anterior tibialis artery blood velocity when used as an adjunct to medical therapy in patients with critical limb ischemia.

Topics: Aged; Blood Flow Velocity; Combined Modality Therapy; Electric Stimulation Therapy; Female; Humans; Iloprost; Ischemia; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Peroneal Nerve; Pilot Projects; Prospective Studies; Regional Blood Flow; Tibial Arteries; Time Factors; Treatment Outcome; Turkey; Ultrasonography, Doppler, Duplex; Vascular Patency; Vasodilator Agents

Patients with peripheral arterial disease (PAD) at stage IIb, pain-free walking distance (PFWD) less than 100 m and unsuitable for revascularization have both impaired quality of life and severe clinical outcome. Aim of the study was to evaluate the efficacy of the prostacyclin analogue iloprost, added to standard therapy, in these patients.. Patients were randomized to receive standard medical therapy (Group A) or standard therapy plus iloprost (Group B), for 1 year. Iloprost was administered for 10 days every 3 months. Treadmill test was performed every 3 months, in Group B before starting the 10-day iloprost cycle.. Fifty patients in Group A and 51 in Group B were enrolled. Mean baseline and 12-month PFWD values were 75.4 ± 21.3 and 128.9 ± 62.9 for iloprost group and 70.3 ± 21.6 and 99.6 ± 62.6 m for controls. Patients treated with iloprost had significantly higher PFWD at 9 and 12 months. This finding was confirmed after carrying forward the last valid observation (124.7 ± 63.4 vs. 88.4 ± 63.1 m, P < 0.01). Major cardiovascular events occurred in 32.0% and 3.9% of patients in Group A and Group B, respectively (P < 0.001). Five patients in Group A died vs. none in Group B (P = 0.02). No serious unexpected adverse reactions occurred in patients receiving iloprost.. Iloprost, added to standard therapy, significantly increases exercise capacity in patients with PAD at severe stage IIb. The percentage of patients who died or experienced major cardiovascular events was significantly lower in patients receiving iloprost. Future studies should focus on the effects of this therapy on clinical outcome.

Topics: Aged; Ankle Brachial Index; Exercise; Exercise Test; Female; Humans; Iloprost; Male; Musculoskeletal Pain; Peripheral Arterial Disease; Pilot Projects; Treatment Outcome; Vasodilator Agents; Walking

Peripheral arteries occlusive disease (PAOD) is a prevalent illness that needs improved pharmacological management, especially for patients not eligible for surgical revascularization. Prostanoids (alprostadil or iloprost) were shown to be effective in PAOD and critical limb ischemia (CLI) but are rather costly. The results of our pharmacoeconomic study (cost estimation based on randomized control trial results) showed that iloprost does not increase cost of treatment when only direct medical costs are taken into account. If indirect costs are included into the analysis iloprost saves up to 27 thousand rubles per patient. Clinical efficacy is still high. Thus iloprost is a better alternative than alprostadil for CLI.

Topics: Alprostadil; Drug Costs; Economics, Pharmaceutical; Female; Follow-Up Studies; Humans; Iloprost; Leg; Male; Middle Aged; Peripheral Arterial Disease; Prostaglandins; Retrospective Studies; Russia

Inflammation is a component in the pathogenesis of critical limb ischemia. We aimed to assess how inflammation affects response to treatment in patients treated for critical limb ischemia using neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocytes ratios (PLR) as markers of inflammation.. Patients in a single tertiary cardiovascular center with critical limb ischemia unsuitable for surgical or interventional revascularization were retrospectively identified. Data were collected on medical history for risk factors, previous surgical or endovascular revascularization, and outcome. A standard regimen of low molecular weight heparin, aspirin, statins, iloprost infusions, and a standard pain medication protocol were applied to each patient per hospital protocol. Patients with improvement in ischemic pain and healed ulcers made up the responders group and cases with no worsening pain or ulcer size or progression to minor or major amputations made up the non-responders group. Responders and Non-responders were compared for risk factors including pretreatment NLR and PLR.. 268 included patients who were not candidates for surgical or endovascular revascularization were identified. Responders had significantly lower pretreatment NLR (4.48 vs 8.47, p < 0.001) and PLR (162.19 vs 225.43, p = 0.001) values. After controlling for associated risk factors NLR ≥ 4.63 (p < 0.001) and PLR ≥ 151.24 (p = 0.016) were independently associated with no response to treatment.. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocytes ratio are markers of inflammation that are reduced in patients improving with medical treatment suggesting a decreased state of inflammation before treatment in responding patients.

Topics: Aged; Cardiovascular Agents; Critical Illness; Female; Humans; Iloprost; Ischemia; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Neutrophils; Peripheral Arterial Disease; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Wound Healing

The aim of this study was to find out if intra-arterial intraoperative iloprost administration, in selected patients undergoing endovascular revascularization procedures, could lead to better results compared with a control group of patients with similar clinical background and risk factors.. We prospectively collected data of consecutive patients undergoing endovascular or hybrid revascularization in the period from June 2017 to August 2019, which were then retrospectively analyzed. Those patients were divided into 2 groups: iloprost and control groups. Inclusion criteria were as follows: the presence of an arteriography that included the foot; Rutherford class 4-6; and Rutherford class 3 with at least 2 cardiovascular risk factors or previous revascularization procedures on the same limb. The intraoperative intra-arterial administration of iloprost was the inclusion criterion for the iloprost group. Patients with a compromised cardiological condition were excluded, as this was a contraindication for iloprost administration. Patients from the 2 groups were matched using the propensity score matching (PSM) methodology of Rosenbaum and Rubin. The primary outcome was freedom from target lesion revascularization (TLR). The secondary outcomes were limb salvage and overall survival.. During the mentioned period, we treated 190 consecutive limbs. The mean follow-up was 11.73 months (median, 10; interquartile range, 5-19). After PSM, the freedom from TLR was significantly better in the iloprost group (78 ± 7%, 74 ± 8%, and 63 ± 9% vs. 67 ± 8%, 50 ± 9%, and 38 ± 10% at 3, 6, and 12 months, respectively; P = 0.043). No significant difference was found in terms of limb salvage (92 ± 5%, 88 ± 6%, and 88 ± 6% vs. 92 ± 4%, 85 ± 6%, and 81 ± 7% at 3, 6, and 12 months, respectively; P = 0.52) and survival (95 ± 3%, 95 ± 3%, and 95 ± 3% vs. 95 ± 4%, 92 ± 5%, and 71 ± 9% at 3, 6, and 12 months, respectively; P = 0.14) between the 2 groups.. These results seem to encourage considering intraoperative use of this adjunct, at least in endovascular revascularization procedures, to improve distal outflow.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Endovascular Procedures; Female; Humans; Iloprost; Infusions, Intra-Arterial; Intraoperative Care; Limb Salvage; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Regional Blood Flow; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vascular Patency; Vascular Surgical Procedures; Vasodilator Agents

Topics: Administration, Intravenous; Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Critical Illness; Drug Administration Schedule; Female; Humans; Iloprost; Ischemia; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Time Factors; Treatment Outcome; Vascular Access Devices; Wound Healing

Previous studies demonstrated that early recoil is frequently observed in patients undergoing balloon angioplasty. The aim of this study was to evaluate the impact of intra-arterial administration of iloprost (Endoprost®, Italfarmaco S.p.A., Milan, Italy) on early elastic recoil after balloon angioplasty of below-the-knee (BTK) vessels in patients with critical limb ischemia (CLI).. Between January 2015 and December 2015 32 patients with CLI underwent balloon angioplasty of at least one BTK vessel followed by intra-arterial administration of iloprost. Early elastic recoil was defined as residual lumen compromise >10%. Early elastic recoil was determined on the basis of minimal lumen diameter (MLD) measurements at baseline (MLDbaseline), immediately after BTK balloon angioplasty (MLDpostdilation), and 15 minutes thereafter (MLD15min).. Patients were predominantly female (18/32, 56.2%) with a mean age of 79.6 years (range 68-87). Most of the patients were diabetics (25/32, 78.1%). An occlusion was present in 24 cases (75%). Mean BTK lesion length was 144.1 mm (range 22-320). Mean MLD measurements were 0.1 mm (range 0-0.5; MLDbaseline), 2.5 mm (range 1.9-3; MLDpostdilation), and 1.9 mm (range 0.7-3; MLD15min). Early elastic recoil was recorded in 14 patients (43.8%). The mean percentage of elastic recoil after 15 minutes was 21.4%.. In our experience intra-arterial administration of iloprost reduces the risk of early elastic recoil after balloon angioplasty of BTK vessels in patients with CLI. Further analyses with larger population studies and randomized trials are needed to validate this therapeutic option.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Critical Illness; Elasticity; Female; Humans; Iloprost; Injections, Intra-Arterial; Ischemia; Leg; Male; Peripheral Arterial Disease; Recurrence; Time Factors; Treatment Outcome; Vascular Patency; Vasodilator Agents

Colour Doppler ultrasonography (CDUS) is very important in general vascular diagnostic procedures. Its role in determining the extent of vasculopathy in Systemic Sclerosis (SSc) needs further investigation. The aim of this study was to compare the presence of altered arteries with nailfold capillaroscopy and clinical signs of ischaemia, that is, digital ulcers or pitting scars (DU/PS). A feasible CDUS protocol is provided.. Two thousand five hundred and twenty-eight arteries of the fingers, palms and wrists from 79 SSc patients (32 arteries per patient) were examined using CDUS. Furthermore, nailfold capillaroscopy, clinical and laboratory data were evaluated.. Narrowed or occluded lumens were seen in 39.8% of all assessable arteries (n = 2489) and 48.9% of all proper palmar digital arteries (n = 1564) but only 15.6% (P < 0.0001) of proximal arteries (n = 924). Fingerwise analyses presented significant coincidence of pathological CDUS findings and DU/PS (P = 0.0009). Pathological CDUS findings were also associated with elevated CRP concentrations, current or past smoking with ⩾20 pack-years, male gender and present or past DU/PS. Receiver operating characteristic curve analysis (area under the curve = 0.727) suggested a cut-off value of ⩾20% pathological vessels (sensitivity: 90.7%; specificity: 47.8%) for the presence of DU/PS. An examination protocol focusing on the right-hand digits II-V (proper palmar digital arteries) revealed similar results (area under the curve = 0.751; sensitivity: 93.0%; specificity: 43.5%).. CDUS of hand and finger arteries allows measurement of the extent of SSc vasculopathy, which is associated with clinical signs of chronic malperfusion. A shortened examination protocol of CDUS (right-hand digits II-V; 15 min instead of 45 min examination time) could complement vascular diagnostics in SSc.

Topics: Adrenergic alpha-Antagonists; Adult; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; C-Reactive Protein; Calcium Channel Blockers; Endothelin Receptor Antagonists; Female; Fingers; Humans; Iloprost; Male; Microscopic Angioscopy; Middle Aged; Peripheral Arterial Disease; Phosphodiesterase 5 Inhibitors; ROC Curve; Scleroderma, Systemic; Sensitivity and Specificity; Skin Ulcer; Smoking; Ultrasonography, Doppler, Color; Vasodilator Agents

Therapeutic guidelines indicate prostacyclin as the first line of treatment in inflammation and vascular diseases. Prostacyclins prevent formation of the platelet plug involved in primary hemostasis by inhibiting platelet activation and, combined with thromboxane, are effective vasodilators in vascular damage. Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease II guidelines indicates prostacyclins; in particular, Iloprost, as the first therapeutic option for treating peripheral arterial disease. However, therapeutic efficacy of Iloprost has witnessed several drawbacks that have occurred in patients receiving repeated weekly administration of the drug by intravenous infusions. Adverse reactions arose under perfusion with Iloprost for 6 h and patient compliance was drastically decreased. Biomedical devices could provide a suitable alternative to overcome these drawbacks. In particular, elastomeric pumps, filled with Iloprost isotonic solution, could slowly release the drug, thus decreasing its side effects, representing a valid alternative to hospitalization of patients affected by peripheral arterial disease. However, the home therapy treatment of patients requires long-term stability of Iloprost in solution-loaded elastomeric pumps. The aim of this work was to investigate the long-term stability of Iloprost isotonic solution in biomedical devices using Turbiscan technology. Turbiscan Lab Expert (L'Union, France) predicts the long-term stability of suspensions, emulsions and colloidal formulations by measuring backscattering and transmission of particulates dispersed in solution. The formulations were evaluated by measuring the variation of physical-chemical properties of colloids and suspensions as a function of backscattering and transmission modifications. In addition, the release profile of Iloprost isotonic solution from the biomedical device was evaluated.

Topics: Automation, Laboratory; Disposable Equipment; Drug Stability; Humans; Iloprost; Infusion Pumps; Infusions, Intravenous; Nephelometry and Turbidimetry; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prostaglandins I; Vasodilator Agents

The objective of this study was to evaluate the incidence of the most severe vascular complications, such as pulmonary arterial hypertension, scleroderma renal crisis, and digital necrosis requiring amputation, in a monocentric group of systemic sclerosis (SSc) patients cyclically treated with intravenous iloprost. We reviewed the record-charts of 115 patients affected by SSc (18 men and 97 women, mean age 58.9.1 ± 14.2 years) regularly receiving iloprost for at least 3 years; the mean duration of the treatment was 98.8 ± 37.5 months (a total of 946.8 years of therapy). Demographic and clinical features were recorded. None of the patients died of SSc-associated vascular complications. After iloprost administration digital gangrene requiring amputation developed in 2 patients who had concomitant peripheral arterial disease (a total of 3 episodes; annual incidence of 0.31 for 100 years of iloprost therapy). Four patients were diagnosed with pulmonary arterial hypertension during iloprost treatment (annual incidence of 0.42 for 100 years of drug therapy); in none of the cases did the complication show a progressive course. No cases of scleroderma renal crisis were observed. With the limits of an observational study and in the absence of a control group, our experience suggests that prolonged cyclic iloprost therapy may limit the incidence/progression of severe digital and visceral SSc-vasculopathy.

Topics: Adult; Aged; Amputation, Surgical; Familial Primary Pulmonary Hypertension; Female; Finger Injuries; Gangrene; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Peripheral Arterial Disease; Scleroderma, Systemic; Severity of Illness Index; Toes; Vasodilator Agents

The study was aimed at assessing feasibility of treatment of patients suffering from critical ischaemia of lower extremities with iloprost as compared to the basic therapy by means of pharmacoeconomic analysis. The findings of clinical studies and meta-analyses demonstrated that therapy with iloprost results in a pronounced clinical effect as compared with the basic therapy: significantly (p<0.005) decreasing the number of amputations above the knee joint (23% versus 39%) and more frequently decreasing the size of trophic ulcers (in 49% of cases versus 26%). This provides maintenance of the ability to work in part of patients and a decrease in the frequency of hospitalization, which in its turn results in decreased costs of treatment and indirect expenses.. The results of the carried out study show that with due regard for only direct costs economy from treatment with iloprost would amount to 1,544,556 Roubles per 100 patients. With additionally taking into account of indirect costs economy from using iloprost as compared with basic therapy increases to 25,689,11 Roubles per 100 patients.

Topics: Amputation, Surgical; Cost Savings; Cost-Benefit Analysis; Disease Management; Drug Costs; Economics, Pharmaceutical; Female; Hospitalization; Humans; Iloprost; Ischemia; Lower Extremity; Male; Medication Therapy Management; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Severity of Illness Index