Updates on the therapeutic approach to pulmonary arterial hypertension

Abstract Pulmonary arterial hypertension (PAH) is a complex, chronic-progressive, debilitating condition with a multifactorial etiology and a severe prognosis. Remodeling of the pulmonary vascular bed leads to significant impairment of hemodynamics, impairment of the right ventricular function, and consequently, a negative effect on exercise capacity, quality of life, and survival of the patients suffering from this condition. Given the nonspecific symptomatology, the diagnosis of PAH is a complex process that requires a stepwise approach and multidisciplinary evaluation. Despite major advances in understanding the underlying mechanisms and developing new therapies, survival rates in PAH patients remain unacceptably low. Current therapies target one of the four identified pathophysiological pathways: the endothelin pathway, the nitric oxide pathway, the prostacyclin pathway, and the activin signaling/bone morphogenetic protein pathway. The treatment of PAH involves a series of general measures, addressing specific circumstances, and administering therapies that are specific to this condition. Assessing the mortality risk of each patient is essential for establishing the initial treatment, and especially, the subsequent therapeutic approach. The main objective in PAH treatment is to achieve and maintain a low-risk status, which is correlated with better survival and improved quality of life for patients. The maximal therapy currently used in PAH is represented by four-drug therapy: endothelin receptor antagonists, phosphodiesterase 5 inhibitors or soluble guanylate cyclase stimulators, prostacyclin analogues or prostacyclin receptor agonists, activin signaling inhibitors. Lung transplantation remains an option for selected patients who exhibit an inadequate response to existing therapies, but it has several limitations due to the complex post-transplant management and limited number of organs available for transplant.