Riociguat in pulmonary arterial hypertension: Application of the 4-strata COMPERA 2.0 risk assessment tool in the PATENT studies

• Published in: Respiratory medicine 2024-12, Vol.236, p.107910, Article 107910
• Main Authors: Hoeper, Marius M., Rosenkranz, Stephan, Badesch, David B., Humbert, Marc, Langleben, David, McConnell, John W., Hegab, Sara, Rahner, Claudia, Richard, Jean-François, Ghofrani, Hossein-Ardeschir
• Format: Article
• Language: English
• Subjects: intermediate-high risk; intermediate-low risk; PAH; pulmonary hypertension
• ISSN: 0954-6111; 1532-3064; 1532-3064
• DOI: 10.1016/j.rmed.2024.107910

Risk stratification is an essential part of evaluating disease severity in patients with pulmonary arterial hypertension (PAH). This study applied the 4-strata COMPERA 2.0 risk model to the Phase 3 PATENT-1/2 studies of riociguat. This was a post hoc analysis of PATENT-1 and PATENT-2. Log-rank tests of Kaplan–Meier curves were performed to compare the risk strata at PATENT-1 baseline and Week 12 regarding time to clinical worsening and survival at 2 years in the PATENT-2 population. Data on COMPERA 2.0 status at baseline were available for 214 patients with riociguat and 100 with placebo; overall, 120 patients were identified as intermediate-low risk and 96 as intermediate-high risk. At PATENT-1 Week 12, improvements in COMPERA 2.0 risk strata and median 6-minute walk distance were seen with riociguat vs placebo in patients assessed as intermediate-low risk and intermediate-high risk at baseline by COMPERA 2.0. More patients improved their COMPERA 2.0 risk status with riociguat vs placebo in the intermediate-low (38 % vs 22 %) and intermediate-high risk groups (42 % vs 31 %). COMPERA 2.0 assessed at PATENT-1 baseline and Week 12 discriminated between risk strata for survival and clinical worsening in PATENT-2 at 2 years (p ≤ .001 for all analyses). In conclusion, this analysis supports the risk-reduction benefits of riociguat in patients with PAH at intermediate-low risk and intermediate-high risk, and externally validated the utility of COMPERA 2.0 in the long-term risk assessment of patients from a clinical trial population. [Display omitted] •Risk stratification is an essential part of disease management in patients with PAH•The COMPERA 2.0 risk assessment model was applied to PATENT-1 and PATENT-2•Riociguat improved COMPERA 2.0 risk strata and 6MWD in PATENT-1•Improvements were seen in patients at intermediate-low and intermediate-high risk•COMPERA 2.0 was associated with survival and clinical worsening in PATENT-2