@article{2ef854ad67714009ba37d75b4800695c,
title = "Risk assessment in pulmonary arterial hypertension: Insights from the GRIPHON study",
abstract = "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.",
keywords = "long-term outcome, low-risk profile, morbidity/mortality, selexipag, treatment",
author = "Olivier Sitbon and Chin, {Kelly M.} and Channick, {Richard N.} and Benza, {Raymond L.} and {Di Scala}, Lilla and Sean Gaine and Ghofrani, {Hossein Ardeschir} and Lang, {Irene M.} and McLaughlin, {Vallerie V.} and Ralph Preiss and Rubin, {Lewis J.} and G{\'e}rald Simonneau and Tapson, {Victor F.} and Nazzareno Gali{\`e} and Hoeper, {Marius M.}",
note = "Funding Information: O.S. has served as a steering committee member for Actelion Pharmaceuticals Ltd; has served as an advisory board member for and received research grants from Actelion Pharmaceuticals Ltd, Bayer, GlaxoSmithKline, and Merck Sharp & Dohme; has received consultancy fees from Actelion Pharmaceuticals Ltd, Arena, Bayer, GlaxoSmithKline, and Merck Sharp & Dohme; has received speaker fees from Actelion Pharmaceuticals Ltd, Bayer, GlaxoSmithKline, and Merck Sharp & Dohme; has served on a scientific advisory board for Arena Pharmaceuticals and Gossamer Bio, and has received writing assistance from Actelion Pharmaceuticals Ltd and GlaxoSmithKline. K.C. has served as a steering committee member for Actelion Pharmaceuticals Ltd; has received research grants from Actelion Pharmaceuticals Ltd, Ironwood Pharmaceuticals, National Institutes of Health, and SoniVie; has served on an advisory board for Bayer Healthcare (through University of California San Diego) and Flowonix; has served as an adjudication committee member for Arena Pharmaceuticals; is Circulation Associate Editor for American Heart Association, and has received consultancy fees from Actelion Pharmaceuticals Ltd. R.C. has served as a steering committee member for Actelion Pharmaceuticals Ltd; has served on an advisory board for Actelion Pharmaceuticals Ltd and Bayer; has received consultancy fees from Bayer and Arena Pharmaceuticals, and has received research grants from Actelion Pharmaceuticals Ltd and United Therapeutics. R.B. has received writing assistance from Actelion Pharmaceuticals Ltd and research grants from Actelion Pharmaceuticals Ltd, United Therapeutics, the American Heart Association, Bayer, the National Institutes of Health/National Heart, Lung, and Blood Institute, PhaseBio, Liquidia, and Abbott. L.D. is an employee of Actelion Pharmaceuticals Ltd and in the past held stock and/or stock options for Actelion Pharmaceuticals Ltd and currently holds stock and/or stock options in the parent company Johnson & Johnson. S.G. has served as a steering committee member for Actelion Pharmaceuticals Ltd; has received speaker fees from Actelion Pharmaceuticals Ltd; has received advisory board fees from Actelion Pharmaceuticals Ltd, and Daiichi-Sankyo; and has served on a data and safety monitoring board for United Therapeutics. H.A.G. has served as a steering committee member for Actelion Pharmaceuticals Ltd; has received advisory board and speaker fees from Actelion Pharmaceuticals Ltd, Bayer, GlaxoSmithKline, Novartis, and Pfizer; has received consultancy fees from Actelion Pharmaceuticals Ltd, Bayer, Bellerophon Pulse Technologies, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Pfizer; and has received research grants from Actelion Pharmaceuticals Ltd and Deutsche Forschungsgemeinschaft. I.L. has served as a steering committee member for Actelion Pharmaceuticals Ltd; has received speaker fees from Actelion Pharmaceuticals Ltd, Merck Sharp & Dohme, and AOP Orphan Pharmaceuticals; and has received research grants from Actelion Pharmaceuticals Ltd and AOP Orphan Pharmaceuticals. V.M. reports grants, personal fees and non-financial support from Actelion Pharmaceuticals Ltd and Bayer; grants from Eiger and SoniVie; and personal fees from United Therapeutics, Arena, Caremark, Medtronic and Merck Sharp & Dohme. R.P. is an employee of Actelion Pharmaceuticals Ltd and in the past held stock and/or stock options for Actelion Pharmaceuticals Ltd and currently holds stock and/or stock options in the parent company Johnson & Johnson. L.R. has served as a steering committee member for Actelion Pharmaceuticals Ltd; and has received consultancy fees from Actelion Pharmaceuticals Ltd, Arena Pharmaceuticals, GeNO Pharmaceuticals, Gilead, Karos Pharmaceuticals, Pfizer, and SoniVie Ltd. G. Simonneau has served as a steering committee member for and received research grants from Actelion Pharmaceuticals Ltd and Bayer; and has received speaker and consultancy fees from Actelion Pharmaceuticals Ltd, Bayer, GlaxoSmithKline, Merck Sharp & Dohme, and Pfizer. V.T. has served as a steering committee member for Actelion Pharmaceuticals Ltd, Bayer, and United Therapeutics; has received consultancy fees from Actelion Pharmaceuticals Ltd, Arena Pharmaceuticals, Bayer, Daiichi-Sankyo, EKOS/BTG, Gilead Sciences, Janssen, Reata, and United Therapeutics; has received research grants from Arena Pharmaceuticals, Arena, Bayer, EKOS/BTG, and Riata; has received speaker fees from Bayer, Gilead Sciences, and Janssen. N.G. is a steering committee member for Actelion Pharmaceuticals; has received grant support, personal fees and non-financial support from Actelion Pharmaceuticals; and has received grant support and personal fees from Bayer Healthcare, Pfizer and GlaxoSmithKline. M.H. has served as a steering committee member for Actelion Pharmaceuticals Ltd; has received speaker and consultancy fees from Actelion Pharmaceuticals Ltd, Bayer, GlaxoSmithKline, Merck Sharp & Dohme, and Pfizer; and has received research grants from Actelion Pharmaceuticals Ltd. Funding Information: Funding was provided by Actelion Pharmaceuticals Ltd, Allschwil, Switzerland. The Sponsor participated in the conception and design of the study, analysis and interpretation of the data, drafting and critical revision of the report, and approved submission of the manuscript. Medical writing support was provided by Laura Corbett of nspm Ltd (Meggen, Switzerland), funded by Actelion Pharmaceuticals Ltd. All authors had full access to all of the data from the study, reviewed and edited the manuscript, approved the final draft, and were involved in the decision to submit the manuscript for publication. The corresponding author had final responsibility for the submission. All authors vouch for the accuracy and completeness of the analyses and for the fidelity of this report to the study protocol. ",
year = "2020",
month = apr,
doi = "10.1016/j.healun.2019.12.013",
language = "English (US)",
volume = "39",
pages = "300--309",
journal = "Journal of Heart and Lung Transplantation",
issn = "1053-2498",
publisher = "Elsevier USA",
number = "4",
}