Prognostic Value of Risk Assessment Tools for Patients with Pulmonary Arterial Hypertension in WHO Functional Class II: A Post Hoc Analysis of the EARLY Trial

Background: Current practice guidelines for patients with Pulmonary Arterial Hypertension (PAH) recommend a multidimensional risk assessment, but World Health Organization (WHO) Functional Class (FC) remains a main criterion for treatment decisions. Objectives: A post hoc analysis was conducted to determine if different risk assessment tools evaluated in PAH registry populations can identify patients in WHO FC II at higher risk of death. Methods: Patients in the randomized, controlled EARLY trial (NCT00091715; N=185), which exclusively enrolled patients in FC II, were stratified into three categories—low-, intermediate-, and high-risk—using the original REVEAL risk calculator, revised REVEAL risk calculator 2.0, COMPERA categorical score, and two FPHN methods (invasive and non-invasive) counting low-risk criteria. Risk of all-cause death was compared between baseline categories. Associations between change in risk category from baseline to month 6 (improved, worsened, or stable) and PAH worsening or death were estimated using a Cox proportional hazards model, adjusting for baseline risk category. Results: Patients classified as intermediate or high risk ranged from 35% using the original REVEAL risk calculator to 89% by the COMPERA method at baseline, and from 37% to 82%, respectively, at month 6. Higher risk category was associated with increased mortality risk. Rates of subsequent PAH worsening and death were higher in patients with worsened risk category and lower in those with improved risk category. Conclusion: Multiparametric assessment has additional prognostic value over FC alone, but different risk assessment tools vary in risk stratification. PAH patients in WHO FC II are not all at low risk, so should be assessed frequently.