Gérald Simonneau1, Lewis J Rubin2, Nazzareno Galiè3, Robyn J Barst4, Thomas R Fleming5, Adaani Frost6, Peter Engel7, Mordechai R Kramer8, Marjana Serdarevic-Pehar9, Gary R Layton10, Olivier Sitbon11, David B Badesch12. 1. University Paris-Sud, National Reference Center for Severe Pulmonary Hypertension, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France. Electronic address: gerald.simonneau@bct.aphp.fr. 2. Department of Medicine, University of California at San Diego, La Jolla, California. 3. Institute of Cardiology, Bologna University Hospital, Bologna, Italy. 4. Division of Pediatric Cardiology, Columbia University, New York, New York. 5. Department of Biostatistics, University of Washington, Seattle, Washington. 6. Department of Medicine, Section of Pulmonary and Critical Care, Baylor College of Medicine, Houston, Texas. 7. Pulmonary Hypertension Program, The Christ Hospital, Cincinnati, Ohio. 8. Pulmonary Institute, Rabin Medical Center, Petah Tikva, Israel. 9. Pfizer Inc, New York, New York. 10. Worldwide Pharmaceutical Operations, Pfizer Ltd, Sandwich, Kent, United Kingdom. 11. University Paris-Sud, National Reference Center for Severe Pulmonary Hypertension, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France. 12. Division of Pulmonary Sciences and Critical Care Medicine, and Cardiology Director, Pulmonary Hypertension Program, University of Colorado Denver, Denver, Colorado.
Abstract
BACKGROUND: In pulmonary arterial hypertension (PAH), adding oral sildenafil to intravenous epoprostenol improved 6-minute walk distance (6MWD) and hemodynamics and delayed time to clinical worsening in a 16-week randomized, placebo-controlled trial (Pulmonary Arterial Hypertension Combination Study of Epoprostenol and Sildenafil [PACES-1]). METHODS: Patients completing PACES-1 could receive sildenafil (titrated to 80 mg, three times daily, as tolerated) in an open-label extension study (PACES-2) for ≥ 3 years; additional therapy was added according to investigator judgment. Survival and changes from PACES-1 baseline in World Health Organization Functional Class and 6MWD were captured. RESULTS: In an open-label setting, 6MWD, an effort-dependent outcome measure, was known to have improved or to have been maintained in 59%, 44%, and 33% of patients at 1, 2, and 3 years, respectively; functional class was known to have improved or to have been maintained in 73%, 59%, and 46%. At 3 years, 66% of patients were known to be alive, 24% were known to have died, and 10% were lost to follow-up. Patients with PACES-1 baseline 6MWD < 325 meters without 6MWD improvement during the first 20 weeks of sildenafil treatment subsequently had poorer survival. CONCLUSIONS: Although reliable assessments of safety and efficacy require a long-term randomized trial, the addition of sildenafil to background intravenous epoprostenol therapy appeared generally to be well tolerated in PAH patients.
RCT Entities:
BACKGROUND: In pulmonary arterial hypertension (PAH), adding oral sildenafil to intravenous epoprostenol improved 6-minute walk distance (6MWD) and hemodynamics and delayed time to clinical worsening in a 16-week randomized, placebo-controlled trial (Pulmonary Arterial Hypertension Combination Study of Epoprostenol and Sildenafil [PACES-1]). METHODS:Patients completing PACES-1 could receive sildenafil (titrated to 80 mg, three times daily, as tolerated) in an open-label extension study (PACES-2) for ≥ 3 years; additional therapy was added according to investigator judgment. Survival and changes from PACES-1 baseline in World Health Organization Functional Class and 6MWD were captured. RESULTS: In an open-label setting, 6MWD, an effort-dependent outcome measure, was known to have improved or to have been maintained in 59%, 44%, and 33% of patients at 1, 2, and 3 years, respectively; functional class was known to have improved or to have been maintained in 73%, 59%, and 46%. At 3 years, 66% of patients were known to be alive, 24% were known to have died, and 10% were lost to follow-up. Patients with PACES-1 baseline 6MWD < 325 meters without 6MWD improvement during the first 20 weeks of sildenafil treatment subsequently had poorer survival. CONCLUSIONS: Although reliable assessments of safety and efficacy require a long-term randomized trial, the addition of sildenafil to background intravenous epoprostenol therapy appeared generally to be well tolerated in PAH patients.
Authors: Rogério Souza; Marion Delcroix; Nazzareno Galié; Pavel Jansa; Sanjay Mehta; Tomás Pulido; Lewis Rubin; B K S Sastry; Gérald Simonneau; Olivier Sitbon; Adam Torbicki; Neli Boyanova; Liliya Chamitava; Claudia Stein; Richard N Channick Journal: Adv Ther Date: 2022-07-12 Impact factor: 4.070
Authors: Nazzareno Galiè; Sean Gaine; Richard Channick; J Gerry Coghlan; Marius M Hoeper; Irene M Lang; Vallerie V McLaughlin; Cheryl Lassen; Lewis J Rubin; Shu-Fang Hsu Schmitz; Olivier Sitbon; Victor F Tapson; Kelly M Chin Journal: Adv Ther Date: 2021-10-30 Impact factor: 3.845