TY - JOUR
T1 - REVEAL risk score in patients with chronic thromboembolic pulmonary hypertension receiving riociguat
AU - Benza, Raymond L.
AU - Farber, Harrison W.
AU - Frost, Adaani
AU - Grünig, Ekkehard
AU - Hoeper, Marius M.
AU - Busse, Dennis
AU - Meier, Christian
AU - Nikkho, Sylvia
AU - Ghofrani, Hossein Ardeschir
N1 - Funding Information:
The CHEST-1 and CHEST-2 studies were supported by Bayer AG (Berlin, Germany). Editorial assistance, specifically table and figure generation, was provided by Adelphi Communications, Ltd. (Bollington, UK), supported by Bayer AG.
Funding Information:
R.L.B. reports grants from Bayer AG, Actelion, EIGER, United Therapeutics, and Gilead paid to his institution, and honoraria from Gilead, Bayer, and Actelion. H.W.F. reports honoraria for lectures and/or consultations from Actelion, Bayer, Gilead, United Therapeutics, and Bellerophon, and grants from Gilead, Actelion, and United Therapeutics. A.F. reports honoraria for lectures and consultations from Actelion, Bayer, Gilead, and Bellerophon, and research grants and research-related support from Actelion, United Therapeutics, Lung LLC, and Gilead. E.G. reports grants from Actelion, Bayer, GSK, Lilly, Miltenyi, Novartis, Pfizer, and United Therapeutics speaker’s bureau fees from Actelion, Alexion, Bayer, GSK, Lilly, Miltenyi, Novarits, Pfizer, and United Therapeutics, and consultancy fees from Actelion, Bayer, GSK, Lilly, Miltenyi, Novartis, Pfizer, and United Therapeutics. M.M.H. reports fees for lectures and/or consultations from Actelion, Bayer, Gilead, GSK, and Pfizer. D.B. is an employee of Chrestos Concept GmbH & Co. KG, Essen, Germany. C.M. and S.N. are employees of Bayer AG, Berlin, Germany. H.-A.G. reports grants from DFG (German Research Foundation), honoraria from Actelion, Bayer, Ergonex, Gilead, GSK, Novartis, and Pfizer, consultancy fees from AbbVie, Actelion, Bayer, Bellerophon Pulse Technologies, Ergonex, Gilead, GSK, Medscape, MSD Sharpe & Dohme, Novartis, OMT, Pfizer, and Web MD Global, and speaker’s bureau fees from Actelion, Bayer, Ergonex, Gilead, GSK, Novartis, and Pfizer.
Publisher Copyright:
© 2018 The Authors
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/7
Y1 - 2018/7
N2 - Background: The REVEAL risk score (RRS) was developed to predict survival in patients with pulmonary arterial hypertension (PAH), based on multiple patient characteristics. Herein we calculated RRS for patients in the randomized CHEST-1 study and open-label CHEST-2 extension study of riociguat in inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). We investigated the effect of riociguat vs placebo on RRS in the CHEST-1 study, and the relationship between RRS and long-term outcomes in the CHEST-2 study. Methods: RRS was calculated post hoc for baseline and Week 16 of CHEST-1 and Week 12 of CHEST-2, based on 9 evaluable elements. Patients were grouped into risk strata by RRS. Relationships between RRS and both survival and clinical worsening-free survival were examined by Kaplan–Meier and Cox proportional hazards analyses. Results: Overall, 237 patients completed CHEST-1 and entered CHEST-2. In CHEST-1, riociguat significantly improved RRS (p < 0.0001) and risk stratum (p < 0.001) vs placebo from baseline to Week 16. RRS at baseline, and at Week 16, and change in RRS during CHEST-1 were significantly associated with survival (hazard ratios for a 1-point reduction in RRS: 0.702, 0.692, and 0.682, respectively) and clinical worsening-free survival (hazard ratios: 0.697, 0.719, and 0.754, respectively) over 2 years in CHEST-2. Conclusions: Riociguat improved RRS in patients with inoperable and persistent/recurrent CTEPH. RRS at baseline and Week 16, and change in RRS from baseline, predicted survival and clinical worsening-free survival. This analysis of RRS in patients with inoperable or persistent/recurrent CTEPH suggests utility for the RRS in indications beyond PAH.
AB - Background: The REVEAL risk score (RRS) was developed to predict survival in patients with pulmonary arterial hypertension (PAH), based on multiple patient characteristics. Herein we calculated RRS for patients in the randomized CHEST-1 study and open-label CHEST-2 extension study of riociguat in inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). We investigated the effect of riociguat vs placebo on RRS in the CHEST-1 study, and the relationship between RRS and long-term outcomes in the CHEST-2 study. Methods: RRS was calculated post hoc for baseline and Week 16 of CHEST-1 and Week 12 of CHEST-2, based on 9 evaluable elements. Patients were grouped into risk strata by RRS. Relationships between RRS and both survival and clinical worsening-free survival were examined by Kaplan–Meier and Cox proportional hazards analyses. Results: Overall, 237 patients completed CHEST-1 and entered CHEST-2. In CHEST-1, riociguat significantly improved RRS (p < 0.0001) and risk stratum (p < 0.001) vs placebo from baseline to Week 16. RRS at baseline, and at Week 16, and change in RRS during CHEST-1 were significantly associated with survival (hazard ratios for a 1-point reduction in RRS: 0.702, 0.692, and 0.682, respectively) and clinical worsening-free survival (hazard ratios: 0.697, 0.719, and 0.754, respectively) over 2 years in CHEST-2. Conclusions: Riociguat improved RRS in patients with inoperable and persistent/recurrent CTEPH. RRS at baseline and Week 16, and change in RRS from baseline, predicted survival and clinical worsening-free survival. This analysis of RRS in patients with inoperable or persistent/recurrent CTEPH suggests utility for the RRS in indications beyond PAH.
KW - chronic thromboembolic pulmonary hypertension
KW - clinical trial
KW - pulmonary
KW - riociguat
KW - soluble guanylate cyclase stimulator
UR - http://www.scopus.com/inward/record.url?scp=85044289708&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044289708&partnerID=8YFLogxK
U2 - 10.1016/j.healun.2018.02.015
DO - 10.1016/j.healun.2018.02.015
M3 - Article
C2 - 29580746
AN - SCOPUS:85044289708
SN - 1053-2498
VL - 37
SP - 836
EP - 843
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 7
ER -