Jean-Luc Vachiéry1, Nazzareno Galiè2, Joan Albert Barberá3, Adaani E Frost4, Hossein-Ardeschir Ghofrani5, Marius M Hoeper6, Vallerie V McLaughlin7, Andrew J Peacock8, Gérald Simonneau9, Christiana Blair10, Karen L Miller10, Jonathan Langley11, Lewis J Rubin12. 1. Cliniques Universitaires de Bruxelles-Hôpital Erasme, Brussels, Belgium. Electronic address: jeanluc.vachiery@erasme.ulb.ac.be. 2. Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy. 3. Hospital Clínic‒Institut d'Investigacions Biomèdiques August Pi i Sunyer and University of Barcelona, Barcelona, Spain, Biomedical Research Networking Center on Respiratory Diseases, Madrid, Spain. 4. Houston Methodist Hospital Lung Center and Weill Cornell Medical College, Houston, Texas, USA. 5. Universities of Giessen and Marburg Lung Center, Giessen, Germany. 6. Hannover Medical School and German Center of Lung Research, Hannover, Germany. 7. University of Michigan Health System, Ann Arbor, Michigan, USA. 8. Regional Heart and Lung Centre, Glasgow, Scotland. 9. Université Paris-Sud, Faculté de Médecine, Le Kremlin Bicêtre, France AP-HP, Centre de Référence de l'Hypertension Pulmonaire Sévère, Département Hospitalo‒Universitaire Thorax Innovation, Service de Pneumologie, Hôpital de Bicêtre, Le Kremlin Bicêtre, France; UMR_S 999, INSERM, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France. 10. Gilead Sciences, Inc., Foster City, California, USA. 11. GlaxoSmithKline, Uxbridge, UK. 12. University of California at San Diego, La Jolla, California, USA.
Abstract
BACKGROUND: In the randomized, double-blind, event-driven AMBITION study, initial combination therapy with ambrisentan and tadalafil was associated with a 50% reduction in risk of clinical failure (first occurrence of all-cause death, hospitalization for worsening pulmonary arterial hypertension [PAH], disease progression, or unsatisfactory long-term clinical response) vs pooled monotherapy. These results were primarily driven by a reduction in PAH-related hospitalization in the combination therapy group, although a significant effect was not observed in a post-hoc analysis of all-cause hospitalization. METHODS: The effect of initial combination therapy with ambrisentan and tadalafil in AMBITION was further explored to study PAH-related hospitalization, which was not reported in the primary publication. RESULTS: Initial combination therapy was associated with a 63% reduction in risk of PAH-related hospitalization when compared with pooled monotherapy (hazard ratio [HR] 0.372, 95% confidence interval [CI] 0.217 to 0.639, p = 0.0002). For every 9 patients treated with combination therapy vs monotherapy, 1 PAH-related hospitalization could be prevented over a 1-year period. Serious adverse events leading to hospitalization, not necessarily PAH-related, occurred in 87 of 253 (34%) and 89 of 247 (36%) of patients on combination therapy and pooled monotherapy, respectively (post-hoc summary). CONCLUSIONS: Initial combination therapy with ambrisentan and tadalafil was found to reduce the risk of PAH-related hospitalization by 63% compared with pooled monotherapy.
RCT Entities:
BACKGROUND: In the randomized, double-blind, event-driven AMBITION study, initial combination therapy with ambrisentan and tadalafil was associated with a 50% reduction in risk of clinical failure (first occurrence of all-cause death, hospitalization for worsening pulmonary arterial hypertension [PAH], disease progression, or unsatisfactory long-term clinical response) vs pooled monotherapy. These results were primarily driven by a reduction in PAH-related hospitalization in the combination therapy group, although a significant effect was not observed in a post-hoc analysis of all-cause hospitalization. METHODS: The effect of initial combination therapy with ambrisentan and tadalafil in AMBITION was further explored to study PAH-related hospitalization, which was not reported in the primary publication. RESULTS: Initial combination therapy was associated with a 63% reduction in risk of PAH-related hospitalization when compared with pooled monotherapy (hazard ratio [HR] 0.372, 95% confidence interval [CI] 0.217 to 0.639, p = 0.0002). For every 9 patients treated with combination therapy vs monotherapy, 1 PAH-related hospitalization could be prevented over a 1-year period. Serious adverse events leading to hospitalization, not necessarily PAH-related, occurred in 87 of 253 (34%) and 89 of 247 (36%) of patients on combination therapy and pooled monotherapy, respectively (post-hoc summary). CONCLUSIONS: Initial combination therapy with ambrisentan and tadalafil was found to reduce the risk of PAH-related hospitalization by 63% compared with pooled monotherapy.
Authors: Mario Naranjo; Valentina Mercurio; Hussein Hassan; Noura Alturaif; Alessandra Cuomo; Umberto Attanasio; Nermin Diab; Sarina K Sahetya; Monica Mukherjee; Steven Hsu; Aparna Balasubramanian; Catherine E Simpson; Rachel Damico; Todd M Kolb; Stephen C Mathai; Paul M Hassoun Journal: ERJ Open Res Date: 2022-05-16