Risk assessment in pulmonary arterial hypertension: Insights from the GRIPHON study

Olivier Sitbon, Kelly M. Chin, Richard N. Channick, Raymond L. Benza, Lilla Di Scala, Sean Gaine, Hossein Ardeschir Ghofrani, Irene M. Lang, Vallerie V. McLaughlin, Ralph Preiss, Lewis J. Rubin, Gérald Simonneau, Victor F. Tapson, Nazzareno Galiè, Marius M. Hoeper

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


BACKGROUND: Approaches to risk assessment in pulmonary arterial hypertension (PAH) include the noninvasive French risk assessment approach (number of low-risk criteria based on the European Society of Cardiology and European Respiratory Society guidelines) and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) 2.0 risk calculator. The prognostic and predictive value of these methods for morbidity/mortality was evaluated in the predominantly prevalent population of GRIPHON, the largest randomized controlled trial in PAH. METHODS: GRIPHON randomized 1,156 patients with PAH to selexipag or placebo. Post-hoc analyses were performed on the primary composite end-point of morbidity/mortality by the number of low-risk criteria (World Health Organization functional class I-II; 6-minute walk distance >440 m; N-terminal pro-brain natriuretic peptide <300 ng/liter) and REVEAL 2.0 risk category. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazard models. RESULTS: Both the number of low-risk criteria and the REVEAL 2.0 risk category were prognostic for morbidity/mortality at baseline and any time-point during the study. Patients with 3 low-risk criteria at baseline had a 94% reduced risk of morbidity/mortality compared to patients with 0 low-risk criteria and were all categorized as low-risk by REVEAL 2.0. The treatment effect of selexipag on morbidity/mortality was consistent irrespective of the number of low-risk criteria or the REVEAL 2.0 risk category at any time-point during the study. Selexipag-treated patients were more likely to increase their number of low-risk criteria from baseline to week 26 than placebo-treated patients (odds ratio 1.69, p = 0.0002); similar results were observed for REVEAL 2.0 risk score. CONCLUSIONS: These results support the association between risk profile and long-term outcome and suggest that selexipag treatment may improve risk profile.

Original languageEnglish (US)
Pages (from-to)300-309
Number of pages10
JournalJournal of Heart and Lung Transplantation
Issue number4
StatePublished - Apr 2020


  • long-term outcome
  • low-risk profile
  • morbidity/mortality
  • selexipag
  • treatment

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation


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