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

Background: 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.

Methods: 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.

Results: 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-min 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).

Conclusions: 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.