Validation of REVEAL Risk Score Calculator 2.0 in Patients with CTEPH in the Phase III CHEST Study

Purpose The REVEAL risk score (RRS) predicts 1-year survival in patients with pulmonary arterial hypertension; it also improved with riociguat in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) in the Phase III CHEST-1 study, and predicted survival and clinical worsening-free survival (CWFS) in the long-term extension CHEST-2. RRS 2.0, an updated RRS, was developed based on modified point values, cut-offs, and variables. This post hoc analysis aimed to validate RRS 2.0 in the CHEST database (a population not derived from REVEAL), as done previously, and assess if the tool discriminates outcomes in a carefully selected and followed patient population. Methods RRS 2.0 was calculated for patients receiving riociguat up to 2.5 mg tid or placebo (pbo) at CHEST-1 baseline (BL) and Week 16, and CHEST-2 Week 12. Only patients enrolled in CHEST-2 were included. Patients were stratified by RRS 2.0 into low (≤7), average/moderately high (8-9), and high/very high (≥10) risk strata at BL and Week 16. Relationship between RRS 2.0 and survival and CWFS in CHEST-2 was examined by Kaplan-Meier and Cox proportional hazards analyses. Results At baseline, mean±SD RRS 2.0 was 7.1±2.7 in riociguat patients (n=155) and 6.9±2.6 in pbo patients (n=82). Risk status at BL was low in 131 patients (55%), average/moderately high in 59 (25%), and high/very high in 47 (20%). At CHEST-1 Week 16, riociguat improved RRS 2.0 by a least squares mean difference of -1.48 vs. pbo (95% CI -1.97 to -0.99; p Conclusion Riociguat improved RRS 2.0 and risk strata in CHEST-1. RRS 2.0 predicted survival and CWFS over two years in CHEST-2. Thus, RRS 2.0 may be a useful tool to predict outcomes in patients with CTEPH. Further assessment of the discriminatory power of RRS 2.0 vs. the original RRS will be done.