Raymond L Benza1, Harrison W Farber2, Adaani Frost3, Ekkehard Grünig4, Marius M Hoeper5, Dennis Busse6, Christian Meier7, Sylvia Nikkho8, Hossein-Ardeschir Ghofrani9. 1. Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA. Electronic address: rbenza@wpahs.org. 2. Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA. 3. Houston Methodist Hospital & Weill Cornell Medical College, Houston, Texas, USA. 4. Center for Pulmonary Hypertension, Thorax Clinic, University Hospital Heidelberg, Heidelberg, Germany. 5. Clinic for Respiratory Medicine, Hannover Medical School, member of the German Center for Lung Research (DZL), Hannover, Germany. 6. Chrestos Concept GmbH & Co. KG, Essen, Germany. 7. Global Medical Affairs, Bayer AG, Berlin, Germany. 8. Global Clinical Development, Bayer AG, Berlin, Germany. 9. University of Giessen and Marburg Lung Center, member of the German Center for Lung Research (DZL), Giessen, Germany; Department of Medicine, Imperial College London, London, UK.
Abstract
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.
RCT Entities:
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.
Authors: Catherine E Simpson; Rachel L Damico; Paul M Hassoun; Lisa J Martin; Jun Yang; Melanie K Nies; R Dhananjay Vaidya; Stephanie Brandal; Michael W Pauciulo; Eric D Austin; D Dunbar Ivy; William C Nichols; Allen D Everett Journal: Chest Date: 2020-01-25 Impact factor: 9.410
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Authors: Yousef Shahin; Samer Alabed; Syed Rehan Quadery; Robert A Lewis; Christopher Johns; Dheyaa Alkhanfar; Maria Sukhanenko; Faisal Alandejani; Pankaj Garg; Charlie A Elliot; Abdul Hameed; Athaniosis Charalampopoulos; James M Wild; Robin Condliffe; Andrew J Swift; David G Kiely Journal: Front Med (Lausanne) Date: 2022-03-14