The new guidelines for the management of pulmonary arterial hypertension (PAH) in adults published by The American College of Chest Physicians (CHEST) is free to view in this month’s online issue of the journal CHEST for patients and clinicians alike.
Full access to the study, entitled “Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults: CHEST Guideline and Expert Panel Report” appears in the August issue of the journal. The new set of guidelines were initially announced in June and covered in a previous report by Pulmonary Hypertension News. The updated guidelines aim to provide advanced, continuing insights into PAH for clinicians, in turn enabling them to optimally guide pharmacological therapy for adult PAH patients.
The full free-access article is available as a PDF format and features 79 recommendations and expert consensus statements, describing the appropriate use of the most recent drug therapies for PAH.
PAH is characterized by a mean pulmonary arterial pressure greater than 25 mm Hg at rest or greater than 30 mm Hg during exercise, and is responsible for progressive and sustained increase in pulmonary vascular resistance leading to right ventricular (RV) failure. Patients suffering from connective tissue diseases, such as scleroderma or liver disease, or infected with HIV are more susceptible to develop PAH. In addition, genetic predisposition also plays a major role in the development of the disease. In the first stages of disease, symptoms are similar to other medical conditions, resulting in a delayed diagnosis until more severe symptoms arise.
Although there have been recent improvements in therapeutic options, PAH is still associated with a high mortality rate, and effective pharmacological treatments are still a challenge for clinicians and their patients. Additionally, the authors stress that an accurate and timely diagnosis is essential before initiating therapy.
Until 15 years ago, the only FDA-approved drug for PAH was epoprostenol, a prostaglandin that inhibits platelet activation and induces vasodilation. Currently, several drugs and delivery-route options exist, all of them discussed in the new CHEST guidelines, including prostanoids, endothelia antagonists, phosphodiesterase inhibitors, a soluble guanylate cyclase stimulator, and calcium channel blockers, which, although not FDA-approved, are often used to treat PAH.
“Treatment of PAH has become a challenging field to keep abreast of due to the increasing number of medications and the large volume of data provided by the clinical studies responsible for their approval. The newly updated CHEST guidelines provide the clinician with a comprehensive approach to the medical management of adult patients with PAH,” said guideline panelist, James R. Klinger, MD, FCCP, Professor of Medicine, Brown University, and PAH guideline topic editor, in a CHEST press release.
There are still not enough clinical studies providing clear and concrete evidence concerning PAH, therefore only 9 of the 79 recommendations in the guidelines are evidence-based. The remaining statements are based on consensus expert advice.
“While these guidelines highlight the best options for treatment today, the process of creating these guidelines shines a light on the lack of sufficient evidence to support stronger recommendations. There are still considerable gaps in trials, research, and understanding the disease,” added Darren Taichman, MD, PhD, FCCP, Adjunct Associate Professor of Medicine, University of Pennsylvania and PAH guideline panel chair, in a CHEST press release. “We hope the community of academic and industry-based researchers will choose carefully those studies that will answer the most important clinical questions so as to best use the limited but generous efforts of our patients, who risk their well-being as volunteer participants in clinical studies.”
PAH is not a common disease, making it difficult to enroll patients in clinical trials in order to obtain useful and relevant clinical data. However, efforts are being made in that direction. Reata Pharmaceuticals, a Texas based drug developer, is currently enrolling patients for its Phase 2 multi-center, double-masked, randomized, dose-ranging, placebo-controlled clinical trial assessing the safety, tolerance, and efficacy of bardoxolone methyl, an antioxidant inflammation modulator in patients suffering from PAH.
Despite current efforts, future studies focusing specifically on the essential clinical questions are needed, this way shortening the current gaps regarding adequate pharmacotherapy for PAH.