Stratification Methods Predict Mortality in Pulmonary Arterial Hypertension

Pulm Hypertension Angiograph
Pulm Hypertension Angiograph
Certain risk stratification methods may help predict the risk for mortality and clinical worsening-free survival in patients with pulmonary arterial hypertension treated with riociguat.

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 ( 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.

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“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

This article originally appeared on Pulmonology Advisor