@article{eb6c799d89b84cd8a9ac5505c96aadfd,
title = "Results of an Expert Consensus Survey on the Treatment of Pulmonary Arterial Hypertension With Oral Prostacyclin Pathway Agents",
abstract = "Background: Treatment of pulmonary arterial hypertension (PAH) has evolved substantially over the past two decades and varies according to etiology, functional class (FC), hemodynamic parameters, and other clinical factors. Current guidelines do not provide definitive recommendations regarding the use of oral prostacyclin pathway agents (PPAs) in PAH. To provide guidance on the use of these agents, an expert panel was convened to develop consensus statements for the initiation of oral PPAs in adults with PAH. Methods: A systematic literature search was conducted using MEDLINE. The established RAND/University of California Los Angeles appropriateness method, which incorporates the Delphi method and the nominal group technique, was used to create consensus statements. Idiopathic, heritable, repaired congenital heart defect, and drug- or toxin-induced PAH (IPAH+) was considered as one etiologic grouping. The process was focused on the use of oral treprostinil or selexipag in patients with IPAH+ or connective tissue disease-associated PAH and FC II or III symptoms receiving background dual endothelin receptor antagonist/phosphodiesterase type 5 inhibitor therapy. Results: The panel developed 14 consensus statements regarding the appropriate use of oral PPAs in the target population. The panel identified 13 clinical scenarios in which selexipag may be considered as a treatment option. Conclusions: The paucity of clinical evidence overall, and particularly from randomized trials in this setting, creates a gap in knowledge. These consensus statements are intended to aid physicians in navigating treatment options and using oral PPAs in the most appropriate manner in patients with PAH.",
keywords = "oral prostacyclin, oral treprostinil, prostacyclin pathway agent, pulmonary arterial hypertension, selexipag",
author = "McLaughlin, {Vallerie V.} and Richard Channick and {De Marco}, Teresa and Farber, {Harrison W.} and Sean Gaine and Nazzareno Gali{\'e} and Krasuski, {Richard A.} and Ioana Preston and Rogerio Souza and Coghlan, {J. Gerry} and Frantz, {Robert P.} and Anna Hemnes and Kim, {Nick H.} and Lang, {Irene M.} and David Langleben and Mengtao Li and Olivier Sitbon and Victor Tapson and Adaani Frost",
note = "Funding Information: Author contributions: All authors completed the PIXEL surveys, had access to the data, contributed to data interpretation and manuscript writing, provided final approval of the manuscript for submission, and have agreed to be accountable for the work in that any questions concerning the work are investigated and resolved. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: V. V. M. is a consultant and/or advisor for Actelion Pharmaceuticals US, Inc, Bayer Corp, Gilead Sciences, Inc, St. Jude Medical, Steadymed Therapeutics, and United Therapeutics Corp. The University of Michigan has received research funding from Actelion Pharmaceuticals US, Inc, Arena Pharmaceuticals, Bayer Corp, Gilead Sciences, Inc, and Eiger BioPharmaceuticals. R. C. has received researched grants from Actelion Pharmaceuticals US, Inc, and Bayer Corp; and is a consultant to Actelion Pharmaceuticals US, Inc, Bayer Corp, ZappRx, Inc, and ThirdPole. T. D. M. is a consultant for Johnson & Johnson/Actelion Pharmaceuticals, United Therapeutics, Arena, and SCOPE/Bial. She is a speaker for Actelion Pharmaceuticals. H. W. F. has received honoraria from Actelion Pharmaceuticals US, Inc, Bayer Corp, and SAB Biotherapeutics. He is a consultant for Actelion Pharmaceuticals, United Therapeutics, Boehringer-Ingelheim, and Bristol-Myers Squibb. He has performed end point adjudication for United Therapeutics. S. G. has received honoraria from Actelion Pharmaceuticals and United Therapeutics. He has received travel grants from Actelion, Novartis, and Menerini. He has performed drug safety board monitoring for United Therapeutics, GSK, and Novartis. N. G. reports grants and personal fees from Actelion, Bayer, GSK, and Pfizer; and personal fees from MSD, all outside the submitted work. R. A. K. is a consultant and receives research funding from Actelion Pharmaceuticals. He is also an investigator for Edwards Lifesciences and is an unpaid member of the scientific advisory board for Ventripoint. I. P. has been a principle investigator on studies sponsored by Actelion, Acceleron, Bayer, Complexa, Liquidia, PhaseBio, Tenax, and United Therapeutics. She has been a steering committee member for Actelion, Acceleron, and Liquidia; and an adjudication committee member for Pfizer. She has served as a consultant for Actelion, Respira, and United Therapeutics; and has reviewed grants for Gilead and United Therapeutics. R. S. has received consultancy fees from Actelion, Bayer, Acceleron, GSK, and Pfizer. J. G. C. has received consultancy fees and honoraria from Actelion Pharmaceuticals, United Therapeutics, GSK, and Bayer; study grants from Actelion Pharmaceuticals; and conference fees from Bayer. R. P. F. is a consultant and steering committee member for Actelion Pharmaceuticals US, Inc; and has served on advisory boards for Abbott and United Therapeutics. A. H. has received grants from the NIH and CMREF. She has served as a consultant for Actelion, Bayer, Complexa, United Therapeutics, and PHPrecisionMed where she also owns equity interest. N. H. K. has received research support from Bellerophon, Eiger, Gossamer Bio, Lung Biotechnology, and SoniVie. He has served as a consultant for Actelion, Arena, Bayer, MSD, and United Therapeutics. He has served on the speakers bureaus for Actelion and Bayer. I. M. L. has relationships with pharmaceutical companies including AOPOrphan Pharmaceuticals AG, Actelion-Janssen (speaker honoraria and grants to the institution), MSD (speaker honoraria), Medtronic (speaker honoraria and travel expenses), and Ferrer (speaker honoraria and travel expenses). D. L. is a consultant and on advisory boards for Acceleron, Actelion, Bayer, Bellerophon, Northern Therapeutics, and PhaseBio. He has received research support from Actelion, Bayer, Eiger, Northern Therapeutics, Reata, and United Therapeutics. He has been on speakers bureaus for Actelion and Bayer. He has received travel and accommodation support from Acceleron, Actelion, Bayer, and Northern Therapeutics. O. S. has received research grants from Actelion, Bayer, GlaxoSmithKline, and MSD. He also has served as a consultant to Actelion, Bayer, Ferrer, Gossamer Bio, MSD, and United Therapeutics. V. T. has served on advisory boards and has received research funding from Actelion, Bayer, and United Therapeutics. He has served on the steering committees for the latter companies, and for Vwave. A. F. has received honoraria and travel expenses for Actelion-sponsored lectures and expert advice litigation related to PH therapies; has received honoraria for consultation and study end point adjudication for United Therapeutics; consults for PhaseBio; and performs data safety monitoring for Complexa. None declared (M. L.). Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript. Other contributions: We thank Dinesh Khanna, MD, University of Michigan, for consultation on Delphi methodology and moderation of the face-to-face panel meeting, which was funded by Actelion Pharmaceuticals. We also thank Kelly Chin, MD, University of Texas, Southwestern Medical Center, for providing her expert opinion to survey questions and Stephen Chan, MD, PhD, University of Pittsburgh School of Medicine, for providing his expert opinion to survey questions and at the face-to-face PIXEL meeting. Medical writing support, funded by Actelion Pharmaceuticals, was provided by Holly Strausbaugh, PhD, and Laura Evans, PharmD, on behalf of Twist Medical. Additional information: The e-Appendix and e-Figure can be found in the Supplemental Materials section of the online article. Funding Information: Other contributions: We thank Dinesh Khanna, MD, University of Michigan, for consultation on Delphi methodology and moderation of the face-to-face panel meeting, which was funded by Actelion Pharmaceuticals. We also thank Kelly Chin, MD, University of Texas, Southwestern Medical Center, for providing her expert opinion to survey questions and Stephen Chan, MD, PhD, University of Pittsburgh School of Medicine, for providing his expert opinion to survey questions and at the face-to-face PIXEL meeting. Medical writing support, funded by Actelion Pharmaceuticals, was provided by Holly Strausbaugh, PhD, and Laura Evans, PharmD, on behalf of Twist Medical. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2020",
month = apr,
doi = "10.1016/j.chest.2019.10.043",
language = "English (US)",
volume = "157",
pages = "955--965",
journal = "CHEST",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "4",
}