Researchers identified risk stratification methods that may help predict the risk for mortality and clinical worsening-free survival in patients with pulmonary arterial hypertension (PAH) treated with riociguat. The findings were according to an analysis of several phase 3, double-blind studies published in the European Respiratory Journal.
The first study included was PATENT-1 (ClinicalTrials.gov Identifier: NCT00810693), in which investigators randomly assigned patients with PAH to placebo, riociguat individually dose adjusted to 2.5 mg maximum dose 3 times daily, or a 1.5-mg exploratory dose of riociguat 3 times per day. In another study, CHEST-1, investigators randomly assigned patients with inoperable chronic thromboembolic PH or persistent/recurrent PH to either placebo or riociguat individually dose adjusted to a 2.5-mg maximum dose 3 times per day.
The investigators obtained data of 6 variables recommended for PAH risk stratification, including the 6-minute walk distance test, World Health Organization Functional Class, N-terminal prohormone of brain natriuretic peptide, right atrial pressure, cardiac index, and mixed venous oxygen saturation. Risk groups/strata were evaluated for correlations with long-term outcomes, including survival and clinical worsening-free survival.
Variables used for PAH risk stratification were used in the French invasive, French noninvasive, and Swedish/COMPERA risk stratification models at baseline and follow-up. In these studies, treatment with riociguat was associated with improvements in risk group/strata in patients with PAH after a 12-week period. Both French noninvasive and Swedish/COMPERA stratification methods were able to discriminate prognosis for survival (P =.0126 and P =.0355, respectively) and clinical worsening-free survival (P =.0001 and P =.0236, respectively). At follow-up, patients who achieved ≥1 low-risk criteria or low-risk stratum had a lower risk for death and clinical worsening vs patients who achieved no low-risk criteria or an intermediate-risk stratum.
A limitation of the analysis, according to the researchers, was the lack of C-indices, which precluded the ability to compare stratification methods statistically.
“In clinical practice,” the researchers concluded, “it is important that individual patient risk should be assessed by experienced treating physicians, as patients may achieve a low-risk category for some parameters and not others.”
Disclosures: Several authors report receiving financial support from various pharmaceutical companies, including Bayer AG, which funded the PATENT and CHEST studies. For a full list of disclosures, please see the reference.
Humbert M, Farber HW, Ghofrani HA, et al. Risk assessment in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension [published online March 28, 2019]. Eur Respir J. doi:10.1183/13993003.02004-2018