Olivier Sitbon1, Kelly M Chin2, Richard N Channick3, Raymond L Benza4, Lilla Di Scala5, Sean Gaine6, Hossein-Ardeschir Ghofrani7, Irene M Lang8, Vallerie V McLaughlin9, Ralph Preiss5, Lewis J Rubin10, Gérald Simonneau11, Victor F Tapson12, Nazzareno Galiè13, Marius M Hoeper14. 1. Hôpital Universitaire de Bicêtre, Université Paris Sud, Le Kremlin-Bicêtre, France. Electronic address: olivier.sitbon@u-psud.fr. 2. UT Southwestern Medical Center, Dallas, Texas. 3. University of California, Los Angeles, Los Angeles, California. 4. Allegheny General Hospital, Pittsburgh, Pennsylvania. 5. Actelion Pharmaceuticals Ltd, Allschwil, Switzerland. 6. National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland. 7. University of Giessen and Marburg Lung Center, member of the German Center of Lung Research, Giessen, Germany; Department of Medicine, Imperial College London, London, United Kingdom. 8. Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Allgemeines Krankenhaus, Vienna, Austria. 9. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan. 10. Division of Pulmonary and Critical Care Medicine, University of California, San Diego, California. 11. Hôpital Universitaire de Bicêtre, Université Paris Sud, Le Kremlin-Bicêtre, France. 12. Cedars-Sinai Medical Center, Los Angeles, California. 13. Department of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy. 14. Department of Respiratory Medicine and German Center of Lung Research, Hannover Medical School, Hannover, Germany.
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 orplacebo. 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.
RCT Entities:
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.
Authors: Olivier Sitbon; Sylvia Nikkho; Raymond Benza; Chunqin Cq Deng; Harrison W Farber; Mardi G Maitland; Paul Hassoun; Christian Meier; Joanna Pepke-Zaba; Krishna Prasad; Werner Seeger; Paul A Corris Journal: Pulm Circ Date: 2020-11-18 Impact factor: 3.017
Authors: Sylvia Nikkho; Peter Fernandes; R James White; Chunqin Cq Deng; Harrison W Farber; Paul A Corris Journal: Pulm Circ Date: 2020-07-20 Impact factor: 3.017
Authors: Adriano R Tonelli; Sandeep Sahay; Kathryn W Gordon; Lisa D Edwards; Andrew G Allmon; Meredith Broderick; Andrew C Nelsen Journal: Pulm Circ Date: 2020-12-14 Impact factor: 3.017
Authors: David Kylhammar; Clara Hjalmarsson; Roger Hesselstrand; Kjell Jansson; Mohammad Kavianipour; Barbro Kjellström; Magnus Nisell; Stefan Söderberg; Göran Rådegran Journal: ERJ Open Res Date: 2021-05-31