Steps forward in the treatment of pulmonary arterial hypertension: latest developments and clinical opportunities

Abstract

Pulmonary arterial hypertension (PAH) is a chronic disease that results in narrowing of the small pre-capillary pulmonary arteries leading to elevation of pulmonary artery pressure and pulmonary vascular resistance, subsequent right ventricular failure, and if unchecked, death. Advances in the treatment of PAH over the last two decades have markedly improved survival. These improvements reflect a combination of changes in treatments, improved patient care strategies, and varying disease phenotypes in the PAH population. Currently approved therapies for PAH are directed at the recognized abnormalities within the pulmonary vasculature and include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclin pathway agents. Most of these drugs have been approved on the basis of short-term trials that mainly demonstrated improvements in exercise capacity. More recently, long-term, event-driven trials of novel drugs have been performed, demonstrating new efficacy parameters. There have also been exciting advances in the understanding of right heart failure pathophysiology in PAH that have the potential to inspire the development of right ventricular targeted therapy and continued discoveries in the heterogeneity of disease and response to treatment has great potential for developing more 'personalized' therapeutic options. In this article, we review the current available data regarding the management of PAH, with an emphasis on the pharmacologic therapies and discussion of novel therapeutic directions for the treatment of this fatal disease.

A Survey-based Estimate of COVID-19 Incidence and Outcomes among Patients with Pulmonary Arterial Hypertension or Chronic Thromboembolic Pulmonary Hypertension and Impact on the Process of Care

“…Advances in PAH management have markedly improved patient survival over the past twenty years. 23 Limitations in access to evaluation, testing, and therapy may have detrimental effects on patient health, even in PAH/CTEPH patients who do not contract COVID-19. We show that centers rapidly incorporated formal telephone and video-enabled visits over a small window of time to mitigate the impact of these disruptions.…”

Paraoxonase-1 Enzyme Activity and Oxidative Status in Pulmonary Hypertension Original Article

“…Contrast to few previous studies, 23,24 in the present study we didn't observe any difference between the PH patients and healthy controls in the means of other oxidative status (TAC, TOS and OSI). There are literature data indicating that the currently approved agents used in the treatment of PH 1,25,26 such as endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and soluble guanylate cyclase stimulators, attenuate the oxidant level. [27][28][29] Additionally, any treatment such as statin, vitamins C and E which has anti-oxidative properties may have some beneficial effects on decreasing the oxidant level.…”

Emerging therapeutics in pulmonary hypertension

“…Current therapies targeting endothelial function and vasodilation/antiproliferation via three major pathways associated with prostacyclin (PGI 2 ), nitric oxide (NO), and endothelin-1 (ET-1) have led to the rapid clinical development of Ͼ10 major Food and Drug Adminisration (FDA)-approved medications for the treatment of PAH ( Fig. 2) (7,61,74,106). In 2013, riociguat, a member of soluble guanylyl cyclase stimulators, has also been approved for the treatment of both PAH and CTEPH (43,44).…”