Pulmonary Arterial Hypertension (PAH) Group 1: Overview, Workup, Risk Stratification, and Current (and Future) Treatment Approaches

Abstract

Abstract: Risk assessment (or risk stratification) and both current and future therapies for pulmonary arterial hypertension (PAH) will be discussed in part B. Risk assessment is key in the initial evaluation and follow-up of persons with PAH. Risk assessment provides information on disease severity and mortality, which, over time, have been incorporated into the application of PAH therapies. After the initial risk assessment, a 4-strata approach is recommended at subsequent follow- up evaluations by the 2022 ERS/ESC pulmonary hypertension (PH) guidelines as described initially in COMPERA 2.0. This method appears to have increased sensitivity to changes in risk from baseline to follow-up and to changes in long-term mortality risk. Current PAH therapies target the prostacyclin, endothelin, and nitric oxide pathways. A sequential approach to therapy has been recommended since publication of the 2009 guidelines and, in the most recent iteration incorporates the 4-strata approach at follow-up. Additional therapy is recommended when intermediate- high or high-risk status is present. New therapies are under active investigation that include targeting novel pathways. Sotatercept, a fusion protein that binds to and sequesters select transforming growth factor β superfamily ligands, is the most promising novel therapy at this time. A recent phase 3, randomized, double-blind, placebo-controlled study in group 1 PAH patients showed a statistically significant improvement in 6-minute walk distance and additional studies of this drug in PH populations are ongoing. Progress in phenotyping this heterogeneous disease is being made, and as PAH therapies continue to evolve, the use of personalized treatment regimens may be possible in the care of this complex, and highly morbid and mortal disease.