Selexipag in Pulmonary Arterial Hypertension: Most Updated Evidence From Recent Preclinical and Clinical Studies

Pulmonary arterial hypertension is a complex disease resulting from the interplay of myriad biological and environmental processes that lead to remodeling of the pulmonary vasculature with consequent pulmonary hypertension. Despite currently available therapies, there remains significant morbidity and mortality in this disease. There is great interest in identifying and applying biomarkers to help diagnose patients with pulmonary arterial hypertension, inform prognosis, guide therapy, and serve as surrogate endpoints. An extensive literature on potential biomarker candidates is available, but barriers to the implementation of biomarkers for clinical use in pulmonary arterial hypertension are substantial. Various omic strategies have been undertaken to identify key pathways regulated in pulmonary arterial hypertension that could serve as biomarkers including genomic, transcriptomic, proteomic, and metabolomic approaches. Other biologically relevant components such as circulating cells, microRNAs, exosomes, and cell-free DNA have recently been gaining attention. Because of the size of the datasets generated by these omic approaches and their complexity, artificial intelligence methods are being increasingly applied to decipher their meaning. There is growing interest in imaging the lung with various modalities to understand and visualize processes in the lung that lead to pulmonary vascular remodeling including high resolution computed tomography, Xenon magnetic resonance imaging, and positron emission tomography. Such imaging modalities have the potential to demonstrate disease modification resulting from therapeutic interventions. Because right ventricular function is a major determinant of prognosis, imaging of the right ventricle with echocardiography or cardiac magnetic resonance imaging plays an important role in the evaluation of patients and may also be useful in clinical studies of pulmonary arterial hypertension.

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A Randomized, Open-Label, 3-Way Crossover Study to Demonstrate Bioequivalence of Sildenafil Powder for Oral Suspension With Tablets Used Commercially and in Clinical Studies for the Treatment of Pulmonary Arterial Hypertension

Clinical Pharmacology in Drug Development ◽

10.1177/2160763x12455172 ◽

2012 ◽

Vol 1 (4) ◽

pp. 152-157 ◽

Cited By ~ 1

Author(s):

X. Gao ◽

M. O'Gorman ◽

J. Cook ◽

H. Shi ◽

R. R. LaBadie

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Crossover Study ◽

Clinical Studies ◽

Oral Suspension ◽

Open Label ◽

Pulmonary Arterial

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Extended-release oral treprostinil in the management of pulmonary arterial hypertension: clinical evidence and experience

Therapeutic Advances in Respiratory Disease ◽

10.1177/1753466618766490 ◽

2018 ◽

Vol 12 ◽

pp. 175346661876649 ◽

Cited By ~ 4

Author(s):

James C. Coons ◽

Taylor Miller

Keyword(s):

Pulmonary Arterial Hypertension ◽

Adverse Effects ◽

Arterial Hypertension ◽

Exercise Capacity ◽

Clinical Studies ◽

Clinical Evidence ◽

Close Monitoring ◽

Long Term Effects ◽

Pulmonary Arterial ◽

Higher Doses

Treprostinil diolamine is the first oral prostacyclin approved for the treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity. Clinical studies have demonstrated modest benefit as monotherapy, whereas no difference in exercise capacity was observed with combination therapy. However, these trials were limited by subtherapeutic dosing owing to intolerable adverse effects. Prostacyclin-related adverse effects, such as nausea, diarrhea, headache, flushing, and jaw pain, are prevalent. More recent pharmacokinetic and clinical studies illustrate the dose–response relationship and the importance of achieving clinically effective doses. Therefore, efforts to improve tolerability are paramount. Oral treprostinil is recommended to be administered three times daily in order to facilitate more rapid titration, higher doses achieved, and improved tolerability. Oral treprostinil has also been studied in carefully selected, stable patients that transitioned from parenteral or inhaled therapy with close monitoring for late deterioration. Ongoing clinical trials will determine the long-term effects of higher doses of oral treprostinil on clinical outcomes. This review describes the clinical evidence and practical experience with the use of oral treprostinil for PAH.

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Cell Therapy for Pulmonary Arterial Hypertension: Potential Efficacy of Endothelial Progenitor Cells and Mesenchymal Stem Cells

Advances in Pulmonary Hypertension ◽

10.21693/1933-088x-11.1.33 ◽

2012 ◽

Vol 11 (1) ◽

pp. 33-38 ◽

Cited By ~ 4

Author(s):

Colin Suen ◽

Shirley H.J. Mei ◽

Duncan J. Stewart

Keyword(s):

Pulmonary Arterial Hypertension ◽

Cell Therapy ◽

Arterial Hypertension ◽

Progenitor Cells ◽

Health Care Providers ◽

Clinical Studies ◽

Great Promise ◽

Care Providers ◽

Endothelial Progenitor ◽

Pulmonary Arterial

Pulmonary arterial hypertension (PAH) presents a challenging problem for health care providers, as effective long-term therapies have been elusive. An emerging paradigm for the pathogenesis of PAH is that endothelial cell injury and apoptosis at the level of the precapillary arteriole could be the initiating event in the pathogenesis of this disease. This hypothesis has spurred research on novel regenerative approaches using stem and progenitor cells. In this review, we compare findings from the latest preclinical and clinical studies using endothelial progenitor cell (EPC) and mesenchymal stem cell (MSC) therapy to treat PAH. Additionally, we highlight recent advances in gene-enhanced cell therapy, an approach that promises to augment the therapeutic potential of EPCs and MSCs especially for the reversal of established PAH. These new regenerative approaches have shown great promise in preclinical studies; however, large, rigorously designed clinical studies will be necessary to establish clinical efficacy.

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