Inhaled Treprostinil Effective in Many Groups of Patients with Pulmonary Hypertension
Presenter: Amber Meservey, MD, Internal Medicine, Duke University Hospital, Durham, NC.
A summary of the session, Outcomes of patients across the spectrum of pulmonary hypertension groups prescribed inhaled treprostinil, October 20, 2021, Chest 2021.
Inhaled treprostinil appears to be effective in decreasing the rates of disease progression in patients with pulmonary hypertension (PH) and various concomitant cardiac and pulmonary diseases, according to this retrospective cohort study presented by Amber Meservey, an investigator for this study. “Discontinuation of inhaled treprostinil was associated with increased risk of disease worsening, irrespective of disease severity,” she said. “We also found that their WSPH [World Symposium on Pulmonary Hypertension] PH disease severity group was not associated with risk of disease worsening among PH patients started on inhaled treprostinil. The major clinical implication of this study was that treatment with inhaled treprostinil in patients with group 1 PH alongside group 2 and/or group 3 PH resulted in similar outcomes as in patients with isolated group 1 disease.”
“PH frequently complicates cardiac and pulmonary conditions,” Meservey explained. “Although we know that development of PH leads to worse outcomes, treatment of PH disproportionate to concomitant heart and lung disease remains controversial. Use of inhaled treprostinil, an inhaled pulmonary vasodilator, was recently approved by the FDA for use in group 3 PH due to interstitial lung disease based on improvement on 6-minute walk distance.”
“Despite a lack of FDA approval, treprostinil is being used clinically for patients who demonstrate clinical characteristics of group 1 physiology out of proportion to their underlying cardiopulmonary condition. We sought to evaluate the impact of inhaled treprostinil treatment on rates of disease progression in patients with PH secondary to a range of World Symposium WSPH groups. As an exploratory objective we also compared disease progression across WSPH groups.”
Meservey and colleagues undertook a retrospective cohort study of 270 patients with PH across WSPH groups who were started on inhaled treprostinil at Duke University Hospital between 2009 and 2017. Subjects had mean pulmonary artery pressure of 25 mm Hg or greater and were categorized according to WSPH groups. The primary outcome was time to disease worsening, which was defined as composite of death, lung transplantation, or transition to IV prostacyclin.
They used a multivariant Cox proportional hazards model to compare time to disease worsening among patients who continued inhaled treprostinil compared with those who had discontinued the medication for at least 7 days. Inhaled treprostinil use was analyzed as a time-dependent covariate and was adjusted for age, sex, and REVEAL Lite 2 score, a validated score of PH severity.
Baseline characteristics show the average age was 64 years, and the majority of patients were female. About 30% had isolated group 1 disease.
“Overall, this was a sick cohort, with 56% of patients being WHO Functional Class III and 24% Class IV at the start of inhaled treprostinil,” Meservey said. “We found no significant difference in baseline characteristics for those who remained on inhaled treprostinil versus those who did not.”
“Baseline physiologic variables were broken down by those who used inhaled treprostinil for more than 3 months and those who had discontinued therapy. Again, we did not find a statistically significant differences between groups. Overall, the average starting 6-minute walk distance was 240 meters and average mean pulmonary arterial pressure was 50 mm Hg.
“We also looked at disease worsening stratified by WSPH group,” Meservey said. “The most favorable outcomes were for patients with isolated group 1 disease and least favorable for mixed group 1, 2, and 3 disease.”
In addition, Meservey said that a multivariate model showed no statistically significant difference with respect to time to disease worsening. “After adjusting for age, sex and REVEAL Lite 2 score, patients who did not continue treatment with inhaled treprostinil had a higher risk of disease progression, with a HR of 5.01. The interaction between inhaled treprostinil continuation and WSPH group was not significant.”
Meservey concluded that results showed that discontinuing inhaled treprostinil was associated with increased risk of disease worsening, irrespective of the patient’s disease severity. Furthermore, for those started on inhaled treprostinil, the patient’s WSPH group did not increase their risk of disease worsening. Clinically, the implications are that treatment with inhaled treprostinil in patients with different PH groups resulted in similar outcomes. However, Meservey cautioned that the study is limited by its retrospective design, and prospective, randomized studies are necessary to confirm the findings.
Disclosures
Amber Meservey, MD: No relationships to disclose.
Reference
Meservey A, Swaminathan A, Parish A, et al. Outcomes of patients across the spectrum of pulmonary hypertension groups prescribed inhaled treprostinil. Presented virtually at: Chest Annual Meeting 2021; October 20, 2021.