Comparison of risk discrimination between reveal risk score calculators in patients from the patent studies of riociguat in pulmonary arterial hypertension

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension (PAH) Disease Management (REVEAL) risk score (RRS) 1.0 and refined RRS 2.0 were developed to predict survival in patients with PAH. To facilitate clinical use, the abridged RRS Lite 1, excluding invasive variables, was developed. This was further refined, excluding non-modifiable variables, to RRS Lite 2. This post hoc analysis compared the four RRS in the 12-week placebo-controlled PATENT-1 study of riociguat (NCT00810693) and assessed predictive accuracy for 1-year long-term outcomes in PATENT-2, the long-term open-label follow-up (NCT00863681). METHODS: RRS 1.0, RRS 2.0, RRS Lite 1, and RRS Lite 2 were calculated for patients receiving either riociguat 2.5 mg three times a day (tid) , 1.5 mg tid–maximum, or placebo at PATENT-1 baseline (BL) and Week 12 (Wk 12). Only patients enrolled in PATENT-2 were included. Predictive accuracy of each RRS for mortality and clinical worsening (CW) at 1 year were compared using receiver operator curve analyses and estimates of C-indices. RESULTS: Data were available for 396 patients who entered PATENT-2. At BL, the four RRS showed almost complete overlap, with most patients having RRS between 4–9. At Wk 12, RRS still overlapped, but were skewed toward lower risk scores due to a reduction of risk in patients treated with riociguat. The majority of RRS were between 3–7. One year after starting PATENT-2, 12 (3%) patients had died. There were few differences between the RRS in prediction of a mortality event. Using BL RRS, C-indices (95% confidence interval) were: RRS 1.0, 0.61 (0.46–0.77); RRS 2.0, 0.58 (0.44–0.72); RRS Lite 1, 0.57 (0.42–0.71); and RRS Lite 2, 0.57 (0.41–0.72). Using Wk 12 RRS, the C-indices were: RRS 1.0, 0.64 (0.51–0.78); RRS 2.0, 0.67 (0.54–0.80); RRS Lite 1, 0.66 (0.53–0.79); and RRS Lite 2, 0.67 (0.54–0.80). After 1 year in PATENT-2, 45 patients (11%) experienced CW. Using BL RRS, C-indices for the four RRS showed similar predictive accuracy: RRS 1.0, 0.67 (0.59–0.76); RRS 2.0, 0.67 (0.58–0.75); RRS Lite 1, 0.66 (0.57–0.75); and RRS Lite 2, 0.67 (0.58–0.76). Using Wk 12 RRS, predictive accuracy was also comparable: RRS 1.0, 0.73 (0.64–0.81); RRS 2.0, 0.75 (0.67–0.83); RRS Lite 1, 0.73 (0.65–0.81); and RRS Lite 2, 0.74 (0.66–0.82). CONCLUSIONS: All RRS confirmed risk decreased from BL to Wk 12 in patients treated with riociguat in PATENT-1. Increased predictive accuracy of Wk 12 RRS highlights the importance of follow-up risk evaluations throughout patient management. Prediction of risk of death or CW was similar across calculators, although further analyses are required in larger patient cohorts with more events. CLINICAL IMPLICATIONS: Despite having fewer variables and excluding invasive variables, the Lite calculators appear to have similar utility in risk prediction compared with the full RRS calculators. 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