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Risk Assessment and Prognosis Based on ESC/ERS Guidelines in Patients With Pulmonary Arterial Hypertension Receiving Riociguat

Marc Humbert

Harrison Farber

Hossein-Ardeschir Ghofrani

Dennis Busse

Christian Meier

Marius Hoeper


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Conference: 2018 PHA International PH Conference & Scientific Sessions

Release Date: 06.28.2018

Presentation Type: Abstracts

File Download: Conference 2018_1075

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2018 International PH Conference and Scientific SeAbstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.


ESC/ERS 2015 treatment guidelines recommend regular risk assessment of patients with pulmonary arterial hypertension (PAH) using a multidimensional approach, including clinical, imaging, exercise, and hemodynamic variables. Patients can be stratified into three risk groups (low, intermediate, and high risk) for mortality at 1 year. Abbreviated versions of this risk assessment were found to discriminate between prognostic groups in incident PAH cohorts of the French, Swedish, and COMPERA registries. [1–3] We evaluated three of these tools in patients with PAH receiving riociguat in the PATENT studies.


In PATENT-1, patients with PAH received placebo or riociguat adjusted up to 2.5 mg three times a day (tid) or 1.5 mg tid (exploratory dose, not included in this analysis) for 12 weeks. For patients entering the PATENT-2 open-label extension study, risk was assessed at baseline and Week 12 according to three methods: 1. French registry invasive analysis: quantified the number of ESC/ ERS low-risk criteria present based on WHO functional class (FC), 6-minute walking distance (6MWD), right atrial pressure (RAP), and cardiac index. 2. French registry noninvasive analysis: quantified the number of low-risk criteria present for WHO FC, 6MWD, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP). 3. COMPERA analysis: assessed WHO FC, 6MWD, NT-proBNP, RAP, cardiac index, and mixed venous oxygen saturation; each was graded 1–3 (1=low risk, 3=high risk) and the rounded mean defined risk category. The association between meeting low-risk criteria at Week 12 of PATENT-1 with long-term outcomes in PATENT-2 was assessed by Kaplan–Meier analyses of observed data. Differences in the long-term outcome between risk groups were analyzed using the log-rank test.


At entry into PATENT-1, approximately 50% of patients were pretreated with a PAH therapy, and the mean time since diagnosis was 2.4 years (1.9 years in treatmentnaïve and 3.0 years in pretreated patients). Patients receiving riociguat 2.5 mg tid in PATENT-1 (n=231) met a greater number of the low-risk criteria or improved their risk status after 12 weeks compared with baseline. Using the French non-invasive method, the number of low-risk criteria at PATENT-1 Week 12 discriminated between prognostic groups for both clinical worsening-free survival (p=0.0001; Figure) and survival (p=0.0126), while the invasive method discriminated for clinical worsening-free survival (p=0.0078) but not overall survival. The COMPERA method discriminated between prognostic groups for both clinical worsening-free survival (p=0.0023) and survival (p=0.0099) based on risk group at Week 12.


This study reproduced the results from an assessment of abbreviated ESC/ERS risk scores in retrospective analyses of registry databases, in a post hoc analysis from a prospective pivotal study database of both incident and prevalent patients receiving riociguat.

1. Boucly A, et al. Eur Respir J 2017;50:1700889;
2. Hoeper MM, et al. Eur Respir J 2017;50:1700740;
3. Kylhammar D, et al. Eur Heart J 2017; doi: 10.1093/

Figure 1: Clinical worsening-free survival stratified by the number of low-risk non-invasive criteria at Week 12 in PATIENT-1.