PURPOSE: The REVEAL risk score (RRS) predicts 1-year survival in patients with pulmonary arterial hypertension (PAH). RRS was shown previously to improve with riociguat in the Phase III PATENT-1 study in patients with PAH and predicted survival and clinical worsening-free survival (CWFS) in the long-term extension PATENT-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 PATENT 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 PATENT-1 baseline (BL) and Week 12, and PATENT-2 Week 12. Only patients enrolled in PATENT-2 were included in the analysis. Patients were stratified by RRS 2.0 into low (/=10) risk strata at BL and Week 12. Relationship between RRS 2.0 and survival and CWFS in PATENT-2 was examined by Kaplan-Meier and Cox proportional hazards analyses. RESULTS: At BL, mean+/-SD RRS 2.0 was 6.5+/-2.6 in riociguat patients (n=231) and 6.4+/-2.2 in pbo patients (n=109). Risk status at BL was low in 213 patients (63%), average/moderately high in 87 (26%), and high/very high in 40 (12%). At PATENT-1 Week 12, patients receiving riociguat had improved RRS 2.0 by a least squares mean difference of -0.95 vs. pbo (95% CI -1.35 to -0.55; p<0.0001); risk status improved in 57% of patients with riociguat and 42% of patients with pbo (p<0.0001). At PATENT-2 Week 12, RRS 2.0 had improved to 5.1+/-2.7 (n=224) and 5.6+/-2.7 (n=107) in riociguat and former pbo patients, respectively. In PATENT-2 (median [range] treatment duration: 139 [0-244] weeks), Cox proportional hazards analyses showed that RRS 2.0 at PATENT-1 BL and Week 12 were significantly associated with survival and CWFS (p<0.0001). Kaplan-Meier analyses showed significant differences in survival and CWFS between patients in the three risk strata at PATENT-1 BL and Week 12 (p<0.0001). CONCLUSION: Riociguat improved RRS 2.0 and risk strata in PATENT-1. RRS 2.0 predicted survival and CWFS over two years in PATENT-2, making RRS 2.0 a useful tool to predict outcomes in patients with PAH. Further assessment of the discriminatory power of RRS 2.0 vs. the original RRS will be done.
- Benza, R. L.
- Farber, H. W.
- Frost, A. E.
- Ghofrani, H. A.
- Corris, P. A.
- Brockmann, B.
- Nikkho, S.
- Meier, C.
- Hoeper, M. M.
