Iloprost In Pulmonary Arterial Hypertension Research Articles

The Efficacy and Safety of Aerosolized Iloprost in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis was conducted to investigate the efficacy and safety of the chronic administration of aerosolized iloprost for pulmonary arterial hypertension (PAH). All the relevant studies were obtained from three databases, namely, PubMed, Web of Science and the Cochrane Library, from the inception of each database to June 1, 2018. In our study, chronic treatment was defined as a period lasting at least 3months. The rate of each event was analyzed by SPSS as a percentage with 95% confidence intervals (CIs). For the meta-analysis, a randomized effect model or a fixed effect model was applied according to the results of the heterogeneity test. Ten studies were included in this study, with a total of 370 patients treated with inhaled iloprost, including 214 in five randomized controlled trials and 156 in five prospective clinical trials. Among the patients who received inhaled iloprost, there was a significant improvement in the 6-min walk distance (6MWD) in the short-medium and prolonged treatment groups. Notably, the functionality improved by at least 1 class in 48.7% of the treated patients. In all the pooled studies, the estimated 3-month, 6-month, 1-year and 2-year event-free survival rates were 96.6%, 92.3%, 62.6% and 39.6%, respectively. In addition, there were eight adverse drug responses. In this systematic review and meta-analysis, inhaled iloprost has been shown to be a safe and well-tolerated agent for PAH in the first 3months after diagnosis. If used for a prolonged period, aerosol iloprost monotherapy could contribute to an unsatisfactory improvement in vascular remodeling and even a decreased event-free survival rate.

Long-term outcomes of domiciliary intravenous iloprost in idiopathic and connective tissue disease-associated pulmonary arterial hypertension.

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.

Clinical utility of inhaled iloprost in pulmonary arterial hypertension

Inhaled iloprost is a drug from the group of prostacyclins used in the treatment of pulmonary arterial hypertension. Its efficacy and safety have allowed its use as monotherapy and combination therapy. This review describes the product characteristics, amenable to treatment groups, and updated clinical evidence of drug use.

Future development of therapy with inhaled iloprost in pulmonary arterial hypertension

Future development of therapy with inhaled iloprost in pulmonary arterial hypertension

Long-term outcome with intravenous iloprost in pulmonary arterial hypertension

Long-term outcome with intravenous iloprost in pulmonary arterial hypertension

Intravenous iloprost for pulmonary arterial hypertension: still waiting for evidence

Irrespective of its aetiology, pulmonary arterial hypertension (PAH) is a serious disorder that results in right ventricular dysfunction, functional impairment and, ultimately, right heart failure and death. Over the last 20 yrs, significant advances in our understanding of the disease have led to the development of new, specific treatments. In 1996, a placebo-controlled trial demonstrated significant survival benefit with intravenous epoprostenol in severe idiopathic PAH 1. Observational studies also suggested epoprostenol was associated with improved long-term outcomes 2, 3. Subcutaneous treprostinil was subsequently shown to improve exercise capacity in PAH 4. More recently, i.v. treprostinil was approved for use by the US Food and Drug Administration in cases of intolerable subcutaneous infusion site pain based on a bioequivalence study 5 and prospective open-label trials 6, 7. Finally, randomised placebo-controlled trials documented the efficacy of inhaled iloprost either as monotherapy 8, or in addition to bosentan 9. These drugs are now part of the recommended treatment algorithm for PAH 10, together with endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. Conversely, data on clinical efficacy of i.v. iloprost in PAH have been scarce. Iloprost is a stable synthetic analogue of prostacyclin 11. It possesses several pharmacological advantages over epoprostenol including enhanced chemical stability at room temperature and increased half-life, resulting in less frequent reservoir changes and the potential to avoid life-threatening events in case of sudden infusion interruption. Short-term open-label 12 and observational 13 studies suggested i.v. iloprost was effective in improving exercise capacity and pulmonary haemodynamics in PAH. However, these studies were limited in …

Long-term outcome with intravenous iloprost in pulmonary arterial hypertension

There is limited data on the long-term efficacy of intravenous iloprost in patients with pulmonary arterial hypertension (PAH). This retrospective multicentre analysis evaluated the clinical course of patients with PAH treated with i.v. iloprost, in most cases after having received inhaled iloprost as first-line therapy. Between 1997 and 2001, 79 PAH patients were treated with i.v. iloprost and followed until 2007. These patients had advanced and progressive disease as indicated by a mean pulmonary vascular resistance of 1,533 dyn x s x cm(-5) at the time of diagnosis and of 1,858 dyn x s x cm(-5) at the onset of i.v. iloprost therapy. Introduction of i.v. iloprost therapy resulted in initial haemodynamic and clinical improvement. At the end of the observation period, however, 50 (61%) patients had died and 21 (26%) required lung transplantation. Transplantation-free survival rates at 1, 3, and 5 yrs were 86%, 59% and 45%, respectively, after the diagnosis of PAH, and 54%, 31% and 15%, respectively, after the introduction of i.v. iloprost therapy. Predictors of an adverse outcome at baseline were a low 6-min walk distance and a low mixed venous oxygen saturation. In conclusion, despite initial haemodynamic and clinical improvement, overall long-term survival with i.v. iloprost therapy was limited.

Inhaled Iloprost in Pulmonary Arterial Hypertension

To review the pharmacology, pharmacodynamics, and clinical trials evaluating inhaled iloprost in pulmonary arterial hypertension (PAH). A MEDLINE search (1996-February 2005) was performed using the key words pulmonary hypertension, iloprost, and epoprostenol. Information regarding Food and Drug Administration approval was obtained via the Internet. All clinical trials using inhaled iloprost in PAH published in English were identified. Additionally, references from the identified articles were reviewed. A stable analog of prostacyclin, inhaled iloprost is thought to promote benefit in PAH through vasodilation, antiproliferative effects, and inhibition of platelet aggregation. In a placebo-controlled trial of 203 patients, inhaled iloprost significantly improved the combined endpoint of change in New York Heart Association functional class and 10% improvement in 6-minute walk distance (p = 0.007). Small, short-term clinical trials demonstrated hemodynamic benefits for inhaled iloprost alone and in combination with other pulmonary vasodilating agents. The aerosolized delivery route and low incidence of adverse events are positive attributes for inhaled iloprost, while the frequency of administration and lack of comparative data limit its role in PAH. Currently, inhaled iloprost offers potential benefit for patients with contraindications to bosentan, preference for non-parenteral products, ineligibility for parenteral therapy, or as adjunctive therapy with other pulmonary vasodilators. Larger, long-term clinical trials are needed to solidify the role for inhaled iloprost in the management of PAH.

Nebulised iloprost in pulmonary arterial hypertension due to eisenmengers syndrome

Eisenmengers syndrome (ES) is a slow progressive disorder characterised by pulmonary arterial hypertension (PAH) leading to right heart compromise. Systemic application of pulmonary vasodilator therapy is complicated by the risk of increased right to left shunt and paradoxical embolism. Nebulised iloprost is an established treatment in PAH leading to functional and symptomatic improvement with the advantage of pulmonary selectivity. We report 10 patients (9 female, 1, male, age 40 [26-58] years) with ES due to ASD (n 5), VSD (n 4), and atrioventicular canal defect (n 1), who were started on nebulised iloprost treatment in a single centre setting. All patients were in NYHA class III and received additional therapy with oxygen, anticoagulation, and diuretics. Iloprost was administered using an ultrasonic nebuliser (Multisonic compact ) in increasing dose up to 140 mcg / 24 hours. 3 patients stopped treatment due to severe side effects, bronchoconstriction in bronchial asthma, and non-compliance. In 7 patients treatment lead to symptomatic improvement in exercise capacity, dyspnoea and fluid retention. In 5 patients who completed a 7 months follow up, 6 minute walk distance (6MWD) significantly improved by 28% from baseline (p 0.002) without deterioration of oxygenation at rest and during exercise (figure, table). Nebulised Iloprost might be a treatment option in PAH in ES that enables symptomatic and functional benefit without worsening hypoxemia.

Intravenous iloprost for treatment failure of aerosolised iloprost in pulmonary arterial hypertension.

Treatment with aerosolised iloprost, a prostacyclin analogue, has beneficial effects in patients with pulmonary arterial hypertension (PAH). It is unclear if patients, whose clinical condition deteriorates under treatment with aerosolised iloprost, benefit from switching to continuous intravenous iloprost. The current authors report on 16 patients with severe PAH who received continuous intravenous iloprost after primary or secondary failure of treatment with aerosolised iloprost. Determinants of efficacy were survival, New York Heart Association (NYHA) class, and walking distance in the 6-min walk test. Of 93 patients with PAH treated with aerosolised iloprost, 16 required switching to intravenous iloprost for clinical deterioration. These patients had severe right heart failure with a cardiac index of 1.6+/-0.2 L x min(-1) x m(-2) and a mixed-venous oxygen saturation of 52+/-6%. Five of these patients showed no improvement and eventually died. Three patients had further deterioration in NYHA class and exercise capacity; two of them underwent lung transplantation; the third patient is still alive. Eight patients showed marked clinical improvement; one underwent lung transplantation and the others are currently alive and stable. In the latter group of patients, the walking distance in the 6-min walk test increased from 205+/-94 to 329+/-59 m. It was not possible to identify clinical or haemodynamic factors that would predict whether switching from inhaled to intravenous iloprost would have a beneficial effect. In patients with pulmonary arterial hypertension who deteriorated while being treated with aerosolised iloprost, switching to continuous intravenous iloprost caused substantial improvement in exercise capacity in eight of 16 patients but could not prevent progression of pulmonary hypertension in the remaining eight patients. Since it was impossible to predict the individual effects of this approach, intravenous prostaglandin treatment should be considered in pulmonary arterial hypertension patients who deteriorate while receiving iloprost aerosol.