Evaluation of patients with severe pulmonary hypertension and a range of comorbidities prescribed inhaled treprostinil.
Date
2024-11
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Attention Stats
Abstract
Background
Patients with pulmonary arterial hypertension (PAH) and additional cardiac or pulmonary comorbidities have a poor prognosis and are frequently excluded from clinical trials. The purpose of this study was to evaluate outcomes of patients with pulmonary hypertension (PH) secondary to a range of World Symposium on PH (WSPH) groups treated with inhaled treprostinil (iTRE) in a real-world setting.Methods
Patients with PH who were started on treatment with iTRE at Duke University were classified by WSPH Group and included patients with Groups 1, 2, 3, combined Groups 2 and 3 (PH in the setting of left heart failure and chronic lung disease), Group 4, and Group 5 PH. Time to disease worsening, a composite of death, lung transplantation, or transition to intravenous prostacyclin was compared by WSPH Group, and iTRE treatment status using a multivariable Cox proportional hazards model adjusted for age, sex, and Registry to Evaluate Early and Long-Term PAH Disease Management Lite 2 risk score. Treatment with iTRE was defined as a time-varying covariate.Results
The cohort included 270 patients with PH: 30.6% Group 1; 10% Group 2; 32.2% Group 3; 11.1% combined Groups 2 and 3; and 15.9% with either Group 4 or 5 PH. At 3 and 6 months of follow-up, 24.8% and 38.9% of patients, respectively, were no longer treated with iTRE. Patients who discontinued treatment with iTRE had a significantly higher risk of disease worsening (adjusted hazard ratio: 5.02, 95% confidence interval: 3.44-7.31). There was no significant difference in disease worsening among WSPH Groups.Conclusions
In a real-world setting, many patients with PH secondary to a range of WSPH Groups tolerated treatment with iTRE. Future studies should phenotype patients with PH based on both comorbidities and therapeutic responsiveness.Type
Department
Description
Provenance
Subjects
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Swaminathan, Aparna C, Amber Meservey, Alice Parish, Cynthia L Green, Kishan Parikh, Terry Fortin, Richard A Krasuski, Jordan W Whitson, et al. (2024). Evaluation of patients with severe pulmonary hypertension and a range of comorbidities prescribed inhaled treprostinil. JHLT open, 6. p. 100131. 10.1016/j.jhlto.2024.100131 Retrieved from https://hdl.handle.net/10161/34041.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Aparna Swaminathan
Cynthia Lea Green
Survival Analysis
Longitudinal Data Analysis
Logistic Regression
Missing Data
Clinical Trial Methods
Maximum Likelihood Methods
Kishan S Parikh
Duke University Medical Center
Duke Clinical Research Institute
Terry Ann Fortin
Richard Andrew Krasuski
Dr. Richard Krasuski is Director of the Adult Congenital Heart Center at Duke University Medical Center, the Director of Hemodynamic Research, and the Medical Director of the CTEPH Program. He is considered a thought leader in the fields of pulmonary hypertension and congenital heart disease. His research focus is in epidemiologic and clinical studies involving patients with pulmonary hypertension and patients with congenital heart disease. He is involved in multiple multicenter studies through the Alliance for Adult Research in Congenital Cardiology (AARCC). He has also helped to develop multiple research databases in these patient populations. He is Co-PI in the upcoming EPIPHANY Study examining the impact of medical and transcatheter interventions on RV-PA coupling in patients with chronic thromboembolic pulmonary hypertension. Over his career he has mentored over 80 students, residents and fellows and has published over 300 peer reviewed publications, book chapters and meeting abstracts. He is also the Chief Editor of Advances in Pulmonary Hypertension and on the editorial boards of several leading medical journals.
Talal I Dahhan
An Internist, Pulmonologist and Critical Care Medicine physician with great interest in diagnosis and management of pulmonary vascular disease, as well as innovations in critical care curricular designs and graduate medical education.
Sudarshan Rajagopal
I am a physician-scientist with a research focus on G protein-coupled receptor signaling in inflammation and vascular disease and a clinical focus on pulmonary vascular disease, as I serve as Co-Director of the Duke Pulmonary Vascular Disease Center. My research spans the spectrum from clinical research in pulmonary vascular disease, to translational research in cardiovascular disease, to the basic science of receptor signaling.
Our basic science resesarch focuses on understanding and untapping the signaling potential of G protein-coupled receptors (GPCRs) to regulate inflammation in vascular disease. GPCRs are the most common transmembrane receptors in the human genome (over 800 members) and are some of the most successful targets for drug therapies. While it has been known for some time that these receptors signal through multiple downstream effectors (such as heterotrimeric G proteins and multifunctional beta arrestin adapter proteins), over the past decade it has been better appreciated that these receptors are capable of signaling with different efficacies to these effectors, a phenomenon referred to as “biased agonism”. Ligands can be biased, by activating different pathways from one another, and receptors can be biased, by signaling to a limited number of pathways that are normally available to them. Moreover, this phenomenon also appears to be common to other transmembrane and nuclear receptors. While a growing number of biased agonists acting at multiple receptors have been identified, there is still little known regarding the mechanisms underlying biased signaling and its physiologic impact.
Much of our research focuses on the chemokine system, which consists of approximately twenty receptors and fifty ligands that display considerable promiscuity with each other in the regulation of immune cell function in inflammatory diseases. Research from our group and others have shown that many of these ligands act as biased agonists when signaling through the same receptor. We use models of inflammation such as contact hypersensitivity and pulmonary arterial hypertension (PAH). PAH is a disease of the pulmonary arterioles that results in right heart failure and most of its treatments target signaling by GPCRs. We use multiple approaches to probe these signaling mechanisms, including in-house pharmacological assays, advanced phosphoproteomics and single cell RNA sequencing.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.