Intravenous prostacyclin-analogue therapy in pulmonary arterial hypertension – A review of the past, present and future

Stubbe, Beate; Opitz, Christian; Halank, Michael; Habedank, Dirk; Ewert, Ralf

doi:10.1016/j.rmed.2021.106336

Cited by 8 publications

(5 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prostacyclin is mainly formed by vascular endothelial cells and plays an important stabilizing role in maintaining the system of the intravascular environment. Prostacyclin binds to specific membranes and simultaneously exhibits the effectiveness of effector cell receptors and, through the association of G proteins and adenylyl cyclase, is able to obtain enhanced intracellular effects of cyclic adenosine monophosphate, which effectively activates protein kinases, reduces cellular concentrations, and produces a number of biological effects, specifically shown to inhibit platelet coagulation, modulate increased inflammation, and strongly relax vascular smooth muscle [ 17 , 18 ].…”

Section: Current Status Of Pah Treatment With Inhaled Formulationsmentioning

confidence: 99%

Advances in the Study of Inhaled Formulations for the Treatment of Pulmonary Arterial Hypertension

Han

Chen

et al. 2022

Applied Bionics and Biomechanics

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) is a serious disease with reduced systemic circulation and low bioavailability associated with conventional and dosed therapy, which inhaled drugs can avoid. A mean pulmonary artery pressure (mPAP) of ≥25 mmHg ( 1 mmHg = 0.133 kPa ) at rest or ≥30 mmHg during exercise and a pulmonary capillary pressure or left atrial pressure (PLA) of ≤15 mmHg can be diagnosed with PAH. Pulmonary hypertension is classified into primary PAH and secondary PAH according to the presence or absence of principles or risk factors. The main symptoms of pulmonary hypertension include dyspnoea, syncope, weakness, chest pain, and the presence of varying degrees of peripheral oedema. It is a highly pathogenic and life-threatening disease and can lead to delays in treatment if not diagnosed in time. In the past few years, the studies related to this progressed slowly, which brought great harm to patients with PAH. Reports showed that patients diagnosed with PAH should receive routine preventative care, such as pneumococcal and influenza vaccinations. Inhalation therapy is mainly used for the treatment of respiratory diseases and is of great interest due to the concentration of the drug in the airways and lung tissues. Therefore, the present situation of pulmonary hypertension and the characteristics of inhalation preparation were reviewed in this paper to provide some related cue for the treatment of pulmonary hypertension. In the future, it is necessary to develop more treatment methods for pulmonary hypertension.

show abstract

Section: Current Status Of Pah Treatment With Inhaled Formulationsmentioning

confidence: 99%

Advances in the Study of Inhaled Formulations for the Treatment of Pulmonary Arterial Hypertension

Han

Chen

et al. 2022

Applied Bionics and Biomechanics

View full text Add to dashboard Cite

show abstract

“…Iloprost was effective for treatment of RP, DU and PAH in SSc patients (112)(113)(114)(115)(116)(117), also decreasing serum levels of ICAM-1, VCAM-1 and E-selectin, reflecting reduced activation of ECs (115). Iloprost and bosentan combinatory therapy increased the number of nailfold capillaries (118).…”

Section: Prostanoidsmentioning

confidence: 99%

Management of Endothelial Dysfunction in Systemic Sclerosis: Current and Developing Strategies

Zanin-Silva

Santana-Gonçalves

Kawashima-Vasconcelos

et al. 2021

Front. Med.

View full text Add to dashboard Cite

Systemic Sclerosis (SSc) is an autoimmune disease marked by dysregulation of the immune system, tissue fibrosis and dysfunction of the vasculature. Vascular damage, remodeling and inadequate endothelial repair are hallmarks of the disease. Since early stages of SSc, damage and apoptosis of endothelial cells (ECs) can lead to perivascular inflammation, oxidative stress and tissue hypoxia, resulting in multiple clinical manifestations. Raynaud's phenomenon, edematous puffy hands, digital ulcers, pulmonary artery hypertension, erectile dysfunction, scleroderma renal crisis and heart involvement severely affect quality of life and survival. Understanding pathogenic aspects and biomarkers that reflect endothelial damage in SSc is essential to guide therapeutic interventions. Treatment approaches described for SSc-associated vasculopathy include pharmacological options to improve blood flow and tissue perfusion and, more recently, cellular therapy to enhance endothelial repair, promote angiogenesis and heal injuries. This mini-review examines the current knowledge on cellular and molecular aspects of SSc vasculopathy, as well as established and developing therapeutic approaches for improving the vascular compartment.

show abstract

“…Intravenous epoprostenol is used to treat adults with severe pulmonary arterial hypertension (PAH) (World Health Organization Group 1) and has been in use worldwide for decades. However, Veletri ® was underused in clinical practice at the time the study started and still remains so to present day, despite available data suggesting a survival benefit if applied early as a part of combination therapy [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Tolerability, safety and survival in patients with severe pulmonary arterial hypertension treated with intravenous epoprostenol (Veletri®): a prospective, 6-months, open label, observational, non-interventional study

et al. 2023

View full text Add to dashboard Cite

Background Epoprostenol AS (Veletri®), a thermostable epoprostenol formulation, provides better drug stability and improved clinical use compared to previous epoprostenol formulations. This study aims to expand clinical experience in the use of Veletri®, especially regarding tolerability, safety and survival. Methods Pulmonary arterial hypertension (PAH) patients at high risk despite pretreatment with at least double oral combination therapy and with clinical indication for epoprostenol (Veletri®) treatment were consecutively included in this prospective, open label, observational, non-interventional study. Clinical data were assessed at baseline, after 3 and 6 months. Adverse events (AEs) and serious adverse events (SAEs) were documented. Survival from initiation of Veletri® was assessed at last patient out. Results Fifteen patients (60 ± 13.7 years, WHO functional class III (n = 10) or IV (n = 5), severely impaired right ventricular function, mean pulmonary arterial pressure 54.8 ± 8.9 mmHg, mean pulmonary vascular resistance 4.4 ± 0.7 (median 3.8) Wood Units) were enrolled and treated with a mean dosage of 7.9 ± 3.9 (median 7.5) ng/kg/min. Eleven patients completed the study (treatment withdrawal n = 1, death n = 3). After a mean follow-up of 19.1 ± 13.5 (median 18.0) months, seven patients died and three were listed for lung transplantation. Seven AEs (nausea n = 3, diarrhea n = 1, flushing n = 2, headaches n = 1) and three SAEs (catheter infection n = 2, catheter occlusion n = 1) were related to Veletri®. The 1- and 2-year survival rates were 73.3% and 52.4%, respectively. Conclusions The study showed that safety and tolerability of epoprostenol AS (Veletri®) was comparable to previous prostacyclin formulations and was feasible for most patients. The maximum tolerable dosage was lower than dosages reported in the literature. In future applications/trials the up-titration process should be pushing for higher dosages of epoprostenol in the occurrence of side effects, as the achievement of a high and effective dosage is crucial for the clinical benefit of the patients. Survival was as expected in these prevalent severely impaired patients. Trial registration The study was registered in the EUPAS registry (EUPAS32492).

show abstract

Intravenous prostacyclin-analogue therapy in pulmonary arterial hypertension – A review of the past, present and future

Cited by 8 publications

References 162 publications

Advances in the Study of Inhaled Formulations for the Treatment of Pulmonary Arterial Hypertension

Advances in the Study of Inhaled Formulations for the Treatment of Pulmonary Arterial Hypertension

Management of Endothelial Dysfunction in Systemic Sclerosis: Current and Developing Strategies

Tolerability, safety and survival in patients with severe pulmonary arterial hypertension treated with intravenous epoprostenol (Veletri®): a prospective, 6-months, open label, observational, non-interventional study

Contact Info

Product

Resources

About