Raymond L Benza1, Harrison W Farber2, Adaani Frost3, Hossein-Ardeschir Ghofrani4, Miguel A Gómez-Sánchez5, David Langleben6, Stephan Rosenkranz7, Dennis Busse8, Christian Meier9, Sylvia Nikkho10, Marius M Hoeper11. 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. University of Giessen and Marburg Lung Center, member of the German Center of Lung Research, Giessen, Germany; Department of Medicine, Imperial College London, London, UK. 5. Hospital General Nuestra Señora del Prado, Centro de Investigación Biomédica en Red de Enfermedade Respiratorias (CIBERES), Talavera de la Reina, Spain. 6. Center for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. 7. Department of Cardiology and Cardiovascular Research Center Cologne, Heart Centre, University Hospital of Cologne, Cologne, Germany. 8. Chrestos Concept GmbH & Co. KG, Essen, Germany. 9. Global Medical Affairs, Bayer AG, Berlin, Germany. 10. Global Clinical Development, Bayer AG, Berlin, Germany. 11. Clinic for Respiratory Medicine, Hannover Medical School, member of the German Center of Lung Research, Hannover, Germany.
Abstract
BACKGROUND: The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) risk score (RRS) calculator was developed using data derived from the REVEAL registry, and predicts survival in patients with pulmonary arterial hypertension (PAH) based on multiple patient characteristics. Herein we applied the RRS to a pivotal PAH trial database, the 12-week PATENT-1 and open-label PATENT-2 extension studies of riociguat. We examined the effect of riociguat vs placebo on RRS in PATENT-1, and investigated the prognostic implications of change in RRS during PATENT-1 on long-term outcomes in PATENT-2. METHODS: RRS was calculated post hoc for baseline and Week 12 of PATENT-1, and Week 12 of PATENT-2. Patients were grouped into risk strata by RRS. Kaplan-Meier estimates were made for survival and clinical worsening-free survival in PATENT-2 to evaluate the relationship between RRS in PATENT-1 and long-term outcomes in PATENT-2. RESULTS: A total of 396 patients completed PATENT-1 and participated in PATENT-2. In PATENT-1, riociguat significantly improved RRS (p = 0.031) and risk stratum (p = 0.018) between baseline and Week 12 compared with placebo. RRS at baseline, and at PATENT-1 Week 12, and change in RRS during PATENT-1 were significantly associated with survival (hazard ratios for a 1-point reduction in RRS: 0.675, 0.705 and 0.804, respectively) and clinical worsening-free survival (hazard ratios of 0.736, 0.716 and 0.753, respectively) over 2 years in PATENT-2. CONCLUSIONS: RRS at baseline and Week 12, and change in RRS, were significant predictors of both survival and clinical worsening-free survival. These data support the long-term predictive value of the RRS in a controlled study population.
BACKGROUND: The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) risk score (RRS) calculator was developed using data derived from the REVEAL registry, and predicts survival in patients with pulmonary arterial hypertension (PAH) based on multiple patient characteristics. Herein we applied the RRS to a pivotal PAH trial database, the 12-week PATENT-1 and open-label PATENT-2 extension studies of riociguat. We examined the effect of riociguat vs placebo on RRS in PATENT-1, and investigated the prognostic implications of change in RRS during PATENT-1 on long-term outcomes in PATENT-2. METHODS: RRS was calculated post hoc for baseline and Week 12 of PATENT-1, and Week 12 of PATENT-2. Patients were grouped into risk strata by RRS. Kaplan-Meier estimates were made for survival and clinical worsening-free survival in PATENT-2 to evaluate the relationship between RRS in PATENT-1 and long-term outcomes in PATENT-2. RESULTS: A total of 396 patients completed PATENT-1 and participated in PATENT-2. In PATENT-1, riociguat significantly improved RRS (p = 0.031) and risk stratum (p = 0.018) between baseline and Week 12 compared with placebo. RRS at baseline, and at PATENT-1 Week 12, and change in RRS during PATENT-1 were significantly associated with survival (hazard ratios for a 1-point reduction in RRS: 0.675, 0.705 and 0.804, respectively) and clinical worsening-free survival (hazard ratios of 0.736, 0.716 and 0.753, respectively) over 2 years in PATENT-2. CONCLUSIONS: RRS at baseline and Week 12, and change in RRS, were significant predictors of both survival and clinical worsening-free survival. These data support the long-term predictive value of the RRS in a controlled study population.
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