iloprost and Connective-Tissue-Diseases

The prostanoids iloprost and alprostadil are widely used to treat ischaemic changes in patients with Raynaud's phenomenon (RP), but the optimal regimen is poorly defined. We evaluated whether there are differences between iloprost and alprostadil, in terms of either clinical efficacy or of laboratory data, with the aim of assisting in the treatment of connective tissue disease (CTD)-associated RP.. Twenty-one women with CTD-associated RP were given intravenous iloprost (11 patients) or alprostadil (10 patients) cyclically (5 consecutive days, followed by 1 day every 30 days). Clinical efficacy (RP symptoms, skin score, digital ulcers) and circulating levels of von Willebrand factor (VWf), tissue plasminogen activator (tPA), thrombomodulin (TM) and Type III procollagen N-terminal propeptide (PIIINP) were evaluated by enzyme-linked immunoassay at different intervals.. The overall benefits of iloprost and alprostadil were similar. RP improved in 45% versus 90% of patients; ulcers in 60% versus 40% of patients (iloprost versus alprostadil). Skin score did not significantly change with either drug. Circulating VWf decreased with either drug (iloprost -6.2%, alprostadil -9.4%), while tPA, TM, and PIIINP remained unchanged. Side effects were only minor and less frequent with alprostadil.. Iloprost and alprostadil were both of benefit in CTD-associated RP, without significant differences in either clinical efficacy or circulating markers. However, ease of handling and the lower price favours alprostadil.

Topics: Adult; Aged; Alprostadil; Biomarkers; Connective Tissue Diseases; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Iloprost; Infusions, Intravenous; Middle Aged; Raynaud Disease; Treatment Outcome; Vasodilator Agents

Topics: Adult; Alprostadil; Connective Tissue Diseases; Female; Fingers; Humans; Iloprost; Male; Middle Aged; Necrosis; Raynaud Disease; Vasodilator Agents

Leg ulcers are a recognised manifestation of cutaneous vasculitis in connective tissue diseases (CTDs) including rheumatoid arthritis (RA). Iloprost a stable prostacyclin analogue has been successfully used to treat Raynaud's phenomenon and digital ulcers associated with CTD's. Our aim was to assess iloprost in the treatment of vasculitic leg ulcers in CTD. In this paper we describe eight cases of vasculitic leg ulceration in association with RA and CTD, treated with intravenous iloprost. The iloprost was administered for 6-8 hours daily and continued for 21-28 days. Immunosuppressive therapy was required in three patients with severe necrotising vasculitis (RAnv). Complete ulcer healing was achieved in four patients within 6 weeks of commencing therapy while rapid improvement occurred in the other four patients. This suggests that iloprost may be useful as an adjunct to therapy for vasculitic leg ulcers. A double-blind placebo controlled study of iloprost therapy for RA leg ulcers is under way.

Topics: Aged; Aged, 80 and over; Arthritis, Rheumatoid; Connective Tissue Diseases; Drug Administration Schedule; Female; Humans; Iloprost; Immunosuppressive Agents; Infusions, Intravenous; Leg Ulcer; Male; Middle Aged; Treatment Outcome; Vasculitis

To determine the effects of short-term, maximum-tolerated-dose and long-term, optimum-dose iloprost treatment of severe pulmonary hypertension associated with systemic sclerosis (SSc) and the primary antiphospholipid syndrome (APS).. Three patients with SSc and 2 with APS who had failed to respond to oral vasodilator therapy for pulmonary hypertension were enrolled in a 32-week, open, prospective trial. Short-term infusion of maximum-tolerated doses and continuous infusion of optimum doses of iloprost were carried out following baseline cardiac catheterization. Catheterization was repeated at 2 and 32 weeks. All 5 patients completed the study and continued therapy for an average of 82 weeks (range 58-103).. Acute infusion of maximum tolerated doses significantly ameliorated the cardiac index (0.92 liters/minute/m2; P < 0.01), pulmonary artery O2 saturation (10.6%; P < 0.05), and pulmonary resistance (-6.7 units; P < 0.05). After 2 weeks of continuous infusion of optimum doses, there was improvement in pulmonary resistance (> or = 16%) and pulmonary artery O2 saturation (> 30%) in the 2 patients with primary APS. After 2 and 32 weeks, the 3 SSc patients showed variable hemodynamic responses. New York Heart Association functional class and exercise tolerance improved in all patients. There was 1 episode of bacteremia, and 1 patient died after 72 weeks of study.. Continuous iloprost infusion may improve exercise tolerance and quality of life in patients with severe pulmonary hypertension associated with SSc and primary APS.

Topics: Adolescent; Adult; Antiphospholipid Syndrome; Connective Tissue Diseases; Exercise Tolerance; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Male; Middle Aged; Prospective Studies; Time Factors

To compare low (0.5 ng/kg/min) and standard dose (2 ng/kg/min) iloprost (a stable carbacyclin analogue of prostacyclin) in patients with Raynaud's phenomenon secondary to connective tissue disorders.. Double blind, random allocation, three six hour infusions on consecutive days. Follow up period eight weeks.. Rheumatology units, five teaching hospitals.. 55 Patients with Raynaud's phenomenon (greater than seven attacks per week), 32 secondary to well documented classical progressive systemic sclerosis (American Rheumatism Association criteria), 11 CREST syndrome, 5 mixed connective tissue disease, 1 rheumatoid arthritis, 1 Sjögren's syndrome, 1 childhood dermatomyositis, and 4 abnormal nailfold capillaroscopy and antibody profiles but no definite diagnosis.. All other treatment for Raynaud's phenomenon was discontinued two weeks before entry. 28 Patients were randomly allocated to receive the low dose, 27 the standard dose. Differing dilutions allowed infusion rates to be started at 10 ml/h with increments of 10 ml/h every 15 minutes until infusion rates reached 0.5 ng/kg/min and 2 ng/kg/min respectively. MAIN OUTCOME MEASURE(s)--Reduction in frequency, duration, and severity of attacks of Raynaud's phenomenon. Assessment of ulcer and ischaemic lesion healing.. Both dosage regimens were equally effective in reducing severity, frequency, and duration of Raynaud's attacks. Ulcer healing occurred to similar degree in both treatment groups (standard dose 44%, low dose 39%). Low dose was associated with significantly fewer side effects.. Both dosage regimens reduce severity of Raynaud's phenomenon and encourage ulcer healing. Low dose was associated with fewer side effects and was better tolerated by the patients.

Topics: Adult; Aged; Connective Tissue Diseases; Double-Blind Method; Humans; Iloprost; Infusions, Intravenous; Middle Aged; Platelet Count; Raynaud Disease; Wound Healing

Pulmonary arterial hypertension (PAH) is a fatal complication in patients with connective tissue disease (CTD).. The objective of the study was to study the prognostic value of the acute pulmonary vasoreactivity test with inhaled iloprost and its association with clinical deterioration in a tertiary care academic medical center.. We conducted a prospective study of patients with CTD and the diagnosis of PAH established by right heart catheterization. Patients were classified into classic responders, partial responders, and non-responders. The association of the pulmonary response and clinical deterioration was analyzed.. We enrolled 25 patients (mean age of 47 ± 13.4 years); 88% were female. The most frequent rheumatologic diagnosis was systemic lupus erythematosus, in 16 (64%) patients. Seventy-two percent of patients were classified as non-responders, and 28% were partial responders. Patients with a partial response had lower right atrial pressure values (5.1 ± 3.1 vs. 8.5 ± 3.2, p = 0.01) and greater systolic pulmonary arterial pressure (87.6 ± 8.1 vs. 72.4 ± 16.2, p = 0.02), compared with non-responders. Non-responders had a tendency for a shorter time to clinical deterioration than partial responders (17.8 vs. 41.1 months, p = 0.052).. Patients with a partial response to the acute pulmonary vasodilator test with inhaled iloprost had a longer clinical deterioration-free period than non-responders.

Topics: Administration, Inhalation; Adult; Blood Pressure; Cardiac Catheterization; Connective Tissue Diseases; Female; Humans; Hypertension, Pulmonary; Iloprost; Lupus Erythematosus, Systemic; Male; Middle Aged; Phenotype; Prognosis; Prospective Studies; Time Factors; Vasodilator Agents

There are few published data on the efficacy of i.v. iloprost in pulmonary arterial hypertension (PAH). We present long-term outcomes in PAH patients receiving i.v. iloprost in a large UK referral centre.. Eighty patients with idiopathic PAH (iPAH, n = 46) or PAH associated with connective tissue disease (CTD-PAH, n = 34) were identified as receiving domiciliary i.v. iloprost between January 1999 and April 2015. Baseline characteristics, doses achieved, functional class at follow-up and survival data were retrieved from hospital databases.. Median maximum dose achieved was 4.6 ng/kg/min in the iPAH group and 5.0 ng/kg/min in CTD-PAH patients. Exercise capacity significantly improved in the first 6 months of therapy in IPAH patients. Overall 1-, 3- and 5-year survival was 78%, 64% and 52% in iPAH (P = 0.002) and 64%, 26% and 21% in CTD-PAH. Independent predictors of survival were age and exercise capacity.. We report improved survival to that previously reported in iPAH patients treated with domiciliary i.v. iloprost. This may be in part related to higher administered doses. Patients with CTD-PAH had poorer survival, reinforcing the need for early transplantation referral in suitable patients.

Topics: Administration, Intravenous; Adult; Connective Tissue Diseases; Female; Humans; Hypertension, Pulmonary; Iloprost; Long Term Adverse Effects; Male; Middle Aged; Survival Analysis; Treatment Outcome; United Kingdom; Vasodilator Agents

Topics: Administration, Intravenous; Connective Tissue Diseases; Disease Management; Humans; Iloprost; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Raynaud Disease; Scleroderma, Systemic

To study the clinical and hemodynamic characteristics of a group of patients with Functional Class (FC) IV pulmonary arterial hypertension (PAH) developing in the presence of diffuse connective tissue diseases (DCTD) and to evaluate the efficacy of intravenous iloprost.. The study enrolled 59 patients with PAN-DCTD, including 7 who had FC IV and 8 who developed this condition during a follow-up. The diagnosis of PAH was based on pulmonary artery catheterization findings. FC IV was diagnosed using the conventional New York Heart Association classification. All the patients received PAH-specific therapy (bosentan, sildenafil); the patients with FC IV had combined therapy; 4 patients were treated with intravenous iloprost calculated with reference to 0.5-2.5 ng/kg/min for 15 days. In addition to the patients with FC IV, 3 patients with unstable FC Ill were given iloprost. Besides targeted therapy, all the patients received standard treatment, including diuretics, and ionotropic therapy.. Evaluation of hemodynamics in patients with different FCs revealed the most important differences in right atrial pressure, cardiac output, cardiac index, and pulmonary vascular resistance. A linear relationship was seen between the level of this indicator and FC, the closest correlation being for hemodynamic parameters characterizing right ventricular systolic function. There were no changes in mean pulmonary artery pressure; only the patients with FC IV were found to have its slight elevation (from 52 ± 15 to 55 ± 11 mm Hg). Pulmonary artery wedge pressure remained unchanged regardless of FC. Intravenous iloprost was noted to have an obvious positive effect on both clinical and hemodynamic parameters. Catheterization verified improvement in 6 out of the 7 patients; no hemodynamic changes were found in 1 patient during 15-day therapy.. The patients with FC IV PAH-DCTD have clinical and hemodynamic features responsible for a fatal prognosis. The results of using intravenous iloprost in patients with decompensated PAH associated with scleroderma systematica convince to use its PAH-specific tablets in cases of verified clinical deterioration when taking its dosage form.. Цель исследования. Изучение клинико-гемодинамических особенностей группы пациентов с легочной артериальной гипертонией (ЛАГ), развивающейся при диффузных заболеваниях соединительной ткани (ДЗСТ) с IV функциональным классом (ФК), и оценка эффективности внутривенного илопроста. Материалы и методы. В исследование включили 59 пациентов с ЛАГ-ДЗСТ, из них у 7 был IV ФК, у 8 такое состояние развилось в процессе наблюдения. Диагноз ЛАГ устанавливали на основании данных катетеризации легочной артерии. IV ФК диагностировали на основании общепринятой классификации Нью-Йоркской ассоциации сердца. Все пациенты получали специфическую для ЛАГ терапию (бозентан, силденафил), пациенты с IV ФК - комбинированную терапию, 4 больным проводили терапию внутривенным илопростом в течение 15 дней из расчета 0,5-2,5 нг/кг/мин. Кроме больных с IV ФК илопрост назначали 3 пациентам с нестабильным III ФК. Помимо целевой терапии, все пациенты получали стандартное лечение, в том числе диуретики, а также инотропную терапию. Результаты. При оценке гемодинамики пациентов разных ФК наиболее значимые различия получены по давлению в правом предсердии, сердечному выбросу, сердечному индексу и легочному сосудистому сопротивлению. Отмечена линейная зависимость между уровнем этих показателем и ФК, причем наиболее тесная корреляция - для гемодинамических показателей, характеризующих систолическую функцию правого желудочка. Изменений среднего ДЛА не выявлено, лишь у пациентов IV ФК отмечено незначимое его повышение (с 52±15 до 55±11 мм рт.ст.). Давление заклинивания легочной артерии оставалось неизменным вне зависимости от ФК. Отмечено очевидное положительное влияние внутривенного илопроста как на клинические, так и на гемодинамические показатели. При катетеризации улучшение подтверждено у 6 пациентов из 7, у 1 больного за 15-дневный курс терапии гемодинамических изменений не выявлено. Заключение. Пациенты с ЛАГ-ДЗСТ IV ФК имеют клинико-гемодинамические особенности, обусловливающие фатальный прогноз. Результаты применения внутривенного илопроста у пациентов с декомпенсированной ЛАГ, ассоциированной с системной склеродермией, убеждают в необходимости применения этой лекарственной формы в случаях подтвержденного клинического ухудшения на фоне приема таблетированных препаратов, специфических для ЛАГ.

Topics: Adult; Aged; Comorbidity; Connective Tissue Diseases; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Middle Aged; Severity of Illness Index; Treatment Outcome; Vasodilator Agents

Intravenous periodic Iloprost is proven effective in the treatment of Raynaud phenomenon (RP) related to connective tissue disorder (CTD). It's well known that synthetic prostaglandins are effective drugs for the treatment of pulmonary arterial hypertension (PAH), and that PAH is frequently associated with CTD.. The aim of the study is to evaluate in the chronic effect of cyclic intravenous Iloprost on pulmonary arterial pressure.. We studied 17 consecutive patients with CTD (14 systemic sclerosis, 3 mixed CTD) and RP, at the entry and after at least 6months of treatment of RP with cyclic Iloprost. On both occasions, in all patients we performed transthoracic Doppler echocardiography and we determined NT-proBNP plasma levels, NYHA functional class, 6 Minute-Walk Distance (6MWD).. At follow-up (8.2±1.9months; range 6-12) mean values of pulmonary arterial systolic pressure (PASP) significantly decreased (from 32.2±9.2 to 29.2±7.6mmHg, p<0.04) and mean values of 6MWD significantly increased (from 407.5±101.5 to 448.3±89.9m, p<0.01). Moreover, we observed a significant direct correlation between PASP and NT-proBNP values and a significant inverse correlation both between NT-proBNP and 6MWD values and between PASP and 6MWD values.. Our results suggest that cyclic intravenous Iloprost may protect against the development or worsening of PAH in patients with CTD and RP.

Topics: Adult; Aged; Cardiovascular Agents; Connective Tissue Diseases; Dose-Response Relationship, Drug; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Male; Middle Aged; Pulmonary Wedge Pressure; Retrospective Studies; Time Factors; Treatment Outcome

To compare the acute hemodynamic effects of adenosine versus iloprost in patients of pulmonary arterial hypertension (PAH) complicated with connective tissue diseases.. During right heart catheterization, 18 patients of PAH complicated with connective tissue diseases sequentially received intravenous infusion of adenosine and inhaled iloprost. After the baseline hemodynamic data were obtained, an adenosine infusion was started and titrated to the maximal tolerated dose. The hemodynamic parameters were allowed to return to baseline. Then inhalation of iloprost was administered. The effects of both medicines on the patient's hemodynamics were monitored.. As compared with the baseline values, the systolic pulmonary artery pressure and pulmonary vascular resistance significantly decreased [(71 +/- 30) vs (80 +/- 29) mm Hg and (712 +/- 440) vs (824 +/- 464) dyn x s x cm(-5) respectively, both P < 0.05) while the heart rate increased significantly [(93 +/- 17) vs (83 +/-16) beat/min, P < 0.05] in the adenosine group. Inhaled iloprost could also lower the systolic pulmonary artery pressure [(66 +/- 29) vs (79 +/- 28) mm Hg, P < 0.05], mean pulmonary artery pressure [(43 +/- 19) vs (52 +/- 19) mm Hg, P < 0.05] and pulmonary vascular resistance [(632 +/- 440) vs (816 +/- 448) dyn x s x cm(-5), P < 0.05] without any effect upon heart rate. Inhaled iloprost exerted more potent effect on lowering mean pulmonary artery pressure and pulmonary vascular resistance than adenosine (P < 0.05). The two medicines did not affect cardiac output, pulse oxygen saturation or systemic blood pressure. The side effects were fewer in the iloprost inhalation group than the adenosine group.. During acute vasodilator testing, inhaled iloprost was more potent than infused adenosine as a pulmonary vasodilator in PAH complicated with connective tissue diseases.

Topics: Adenosine; Adult; Antihypertensive Agents; Blood Pressure; Cardiac Catheterization; Connective Tissue Diseases; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Middle Aged; Prospective Studies; Vasodilation; Vasodilator Agents; Young Adult

Nebulised iloprost is established therapy of severe pulmonary hypertension; however, the effects on the bronchoalveolar compartment have not been investigated so far. We studied the short- and long-term effects of nebulised iloprost on pulmonary function tests and gas exchange in 63 patients with severe pulmonary hypertension (idiopathic n=17, chronic thromboembolism n=15, connective tissue disease n=12, congenital heart disease n=11, respiratory diseases n=8). Patients received iloprost in increasing dose up to 140 micro g iloprost/24h via an ultrasonic nebuliser. Short-term effects were assessed before and after every nebulisation: peak expiration flow decreased in mean by 1.9% (423+/-98 to 415+/-98) and percutaneous oxygen saturation increased in mean by 0.7% (90+/-6 to 91+/-5) post-nebulisation. There were no significant differences concerning underlying diagnosis or dose of nebulised iloprost. Within 3 months, 9 patients stopped treatment due to non-compliance with frequent nebulisations (n=3), or severe side effects (n=4); 2 patients with additional obstructive lung disease developed bronchoconstriction. Long-term effects were assessed by pulmonary function tests and gas exchange parameters at baseline and after 3 months treatment. There were no significant differences after 3 months therapy neither in FEV(1), FVC, TLC, residual volume nor in diffusions capacity, SO(2) at rest and during 6 min walking test, also in respect of the underlying diseases. However, there was a significant increase in 6 min walking distance (6 MWD) after 3 months (246+/-113 to 294+/-115 m, P<0.05). In conclusion, treatment with nebulised iloprost leads to functional improvement in severe pulmonary hypertension without systematic adverse short- and long-term effects on pulmonary function test or gas exchange. Patients with additional obstructive lung disease might develop bronchoconstriction. Severe side effects leading to discontinuation of treatment occurred in 9% of patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Connective Tissue Diseases; Female; Forced Expiratory Flow Rates; Heart Diseases; Humans; Hypertension, Pulmonary; Iloprost; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Pulmonary Embolism; Respiratory Function Tests; Sulfur Dioxide; Treatment Outcome; Vasodilator Agents; Vital Capacity

We analysed our experience with the use of iloprost for the treatment of critical ischaemic digits (ID) in children with connective tissue diseases (CTD) in order to assess its safety and efficacy.. This was a retrospective analysis of paediatric patients with CTD who were treated with iloprost for critical ID resistant to conventional therapy. Information on demographics, clinical and laboratory features, the regimen of iloprost treatment and outcome were collected.. Fifteen patients (10 female, five male) treated one or more times with iloprost were included (total of 19 treatments). Six had juvenile systemic sclerosis, five had systemic lupus erythematosus, three had mixed connective tissue disease and one had cutaneous polyarteritis nodosa. Thirteen patients were already taking calcium channel blockers with no improvement; in two patients ID were the presenting signs of the disease without prior treatment. Eleven patients had more than two fingers involved; one child had involvement of all 10 fingers. Normal digital blood flow was achieved in 74% of treatments and significant improvement was noted in 26%. Fingertip necrosis was present in 11 patients (14 treatments). It healed completely in seven, improved in one and remained unchanged in six. Raynaud's phenomenon (RP) was present in 14 patients (17 treatments): in two no RP attack occurred during the follow-up period, eight improved both in the number of attacks per week and in the duration of each attack. Complete pain relief was observed in 10/17 treatments (59%) and there was a significant decrease in pain in the remaining seven. No major side-effects or withdrawal symptoms were reported. Minor side-effects reported include reversible headache (seven patients), hypotension or irritability (three), nausea/vomiting (two) and injection site reaction (one).. Iloprost appears to be a safe and effective treatment for ischaemic digits and digital ulcers in children with CTD. In conjunction with immunosuppressive drugs, it has a potential role in preventing irreversible complications, such as digital gangrene and amputation.

Topics: Adolescent; Child; Child, Preschool; Connective Tissue Diseases; Drug Administration Schedule; Female; Fingers; Humans; Iloprost; Infant; Infusions, Intravenous; Ischemia; Male; Retrospective Studies; Treatment Outcome; Vasodilator Agents

The authors have evaluated the effects of long-term treatment of digital vasculitis secondary to various types of connective tissue disease, Systemic Lupus Erythematosus (SLE), Progressive Systemic Sclerosis (PSS), Sjögren's Syndrome (SS), using iloprost. The drug has proven to be effective both in reducing pain and clinical symptoms induced by vasospastic phenomena, as well as in promoting the healing of serious acral ischemic lesions. In the patient with LES, clinical modifications of the local vasculitic phenomena have been associated with a contemporaneous remission of the disease. The persistence of the drug's clinical effects even after suspension of treatment, instrumental and biohumoral changes and concomitant systemic effects on the disease lead to the conclusion that the drug's effect, is not merely due its vasodilating action and its ability to interfere with the coagulative process, but rather must be sought within the context of a morpho-structural repair of the microcirculation.

Topics: Adult; Aged; Connective Tissue Diseases; Drug Tolerance; Female; Fingers; Humans; Iloprost; Middle Aged; Raynaud Disease; Vasculitis

One hundred and twenty seven patients who had Raynaud's attacks secondary to connective tissue disease received intravenous infusions of iloprost in controlled clinical trials. Results of previous treatments for Raynaud's attacks had been recorded by clinicians in 84 of these cases, allowing a comparison to be made with the response to iloprost treatment. Iloprost was reported by the patients as beneficial in 49 (58%) of 84 cases, whereas only 36 (43%) of the 84 patients had previously found any other treatment to be useful. Twenty four of 48 (50%) patients who had not responded to any previous treatment found iloprost to be of benefit. Success or failure of treatment with iloprost was not accurately predicted by the result of treatment with any other drug, except prostacyclin. This survey suggests that iloprost is a useful treatment for patients with severe secondary Raynaud's phenomenon and can be effective in patients unresponsive to other treatments.

Topics: Connective Tissue Diseases; Humans; Iloprost; Infusions, Intravenous; Nifedipine; Raynaud Disease; Retrospective Studies