Reply to the letter to the editor entitled “Bridging the species divide: The limits of rat models in capturing human PVOD mechanisms” by Perros F. et al.

To the Editor,
We read with great interest the recent paper by Prabhakar et al., “Mechanisms underlying age-associated exacerbation of pulmonary veno-occlusive disease,”1 which investigates the role of the integrated stress response (ISR) in pulmonary veno-occlusive disease (PVOD).

Pulmonary arterial hypertension (PAH) is a severe disease caused by progressive distal pulmonary artery obstruction. One cause of PAH are loss-of-function mutations in the potassium channel subfamily K member 3 (KCNK3). KCNK3 encodes a two-pore domain potassium channel, which is crucial for pulmonary circulation homeostasis. 

The objective of this analysis was to compare clinician-based and formally calculated risk assessments by REVEAL Lite 2 and COMPERA 2.0 and to characterize parenteral prostacyclin utilization within 90 days of baseline in high-risk patients. A multisite, double-blind, retrospective chart review of patients with pulmonary arterial hypertension (PAH) was conducted with an index period of January 2014–March 2017.

This real-world study explored factors affecting persistence with macitentan and selexipag treatment from the perspective of 23 healthcare professionals (HCPs) and 134 patients with pulmonary arterial hypertension between 2019 and 2022. Continuous patient/HCP communication and education were key drivers of persistence, as were early discussion and management of side effects.