Prostacyclin analogue benefit consistent in PAH patients with underlying cardiovascular conditions
Presenter: Jean M. Elwing, MD, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH
Efficacy of oral treprostinil in patients with pulmonary arterial hypertension with and without cardiovascular comorbidities. Session: Pulmonary Vascular Disease Posters 3. Presented Oct 10, 2023.
Oral treprostinil reduces the risk of clinical worsening in patients with pulmonary artery hypertension (PAH) regardless of whether they have cardiovascular comorbidities. Moreover, the efficacy of oral treprostinil is not affected by the number of cardiovascular comorbidities, according to results of this post hoc analysis of the randomized, placebo-controlled FREEDOM-EV study presented at CHEST 2023.
In this analysis, event rates were numerically similar for patients with or without cardiac comorbidities affecting approximately 25% to 26% in each of several cohorts evaluated, according to presenter Jean M. Elwing, MD, of the Department of Medicine at the University of Cincinnati College of Medicine in Cincinnati, Ohio.
“The clinical worsening data for each cohort very closely mirror the overall FREEDOM-EV population data, suggesting that oral treprostinil benefits patients with and without cardiovascular morbidities,” said Dr. Elwing.
The findings of this study are important given the increasing number of patients with PAH who present with cardiovascular comorbidities, she said. In the 2022 PAH clinical practice guidelines from the European Society of Cardiology and the European Respiratory Society, authors emphasized the need to assess cardiovascular comorbidities when making treatment decisions. Patients with cardiopulmonary comorbidities have poorer responses to PAH medication, a higher likelihood of nonadherence to treatment, and a higher risk of mortality compared to PAH patients with no cardiopulmonary comorbidities, according to the guidelines.
Negative impact on response to initial oral combination therapy was demonstrated in a recent study that included 181 treatment-naive patients with PAH. Results showed cardiovascular comorbidities were associated with a less effective response to treatment. More specifically, treatment-induced decreases in pulmonary vascular resistance were observed for patients with 1 cardiac comorbidity, and even more for those with 2 or more cardiac comorbidities.
In most patients in that study, initial oral therapy was the combination of the endothelin receptor antagonist ambrisentan and the PDE5 inhibitor tadalafil. By comparison, the efficacy of prostacyclin therapies in PAH patients with cardiovascular comorbidities is less well understood, Dr Elwing said.
Accordingly, Dr Elwing and co-investigators performed a post hoc analysis of FREEDOM-EV, the global, randomized, double blind, placebo-controlled study. For the analysis, 3 groups were defined based on the number of cardiovascular comorbidities in patients’ medical histories (none, 1 or more, and 2 or more).
The most common cardiovascular comorbidity among patients in FREEDOM-EV was hypertension. Among patients with at least 1 cardiovascular comorbidity, hypertension was present in 28% of the oral treprostinil-treated group and 25% of the placebo-treated group. Other common cardiovascular comorbidities included hypercholesterolemia in 13% to 14% of patient subsets, heart arrythmias in 11% to 12%, and diabetes mellitus in 9% to 10%.
Previously published results of the FREEDOM-EV study showed that in patients with PAH, oral treprostinil reduced the risk of clinical worsening compared to placebo when added to oral monotherapy. In the overall data from the study, clinical worsening events were seen in 26% of participants in the oral treprostinil group (n = 90) and 36% of participants in the placebo group (n = 124).
In the present post hoc analysis, clinical worsening events were seen in similar proportions of patients, data presented at CHEST 2023 show. Clinical worsening events were seen in 26% of patients with no cardiovascular comorbidities, 26% of patients with at least 1 comorbidity, and 25% of patients with 2 or more.
Moreover, hazard ratios (HRs) between the groups closely mirrored the overall FREEDOM-EV population data. The overall baseline risk-adjusted HR was 0.61 (95% confidence interval [CI] 0.46-0.81; P < .001). In the post hoc analysis reported here, HRs were 0.63 (95% CI, 0.43-0.93; P = .021) for the no-comorbidity group, 0.60 (95% CI, 0.40-0.90; P = .013) for the 1 or more comorbidity group, and 0.52 (95% CI, 0.30-0.91; P = 0.022) for the 2 or more group.
“Oral treprostinil reduces the risk of clinical worsening irrespective of the presence of cardiovascular comorbidities,” Dr. Elwing and co-authors concluded in the abstract.
Disclosures
The study was sponsored by United Therapeutics. Jean Elwing reported Consulting/Advising with United Therapeutics, Altavant, Aerovate, Bayer, Gossamer Bio, Liquida, Acceleron/Merck, Janssen, and Insmed. She also reported Research Support/Grants with United Therapeutics, Gossamer Bio, Bayer, Acceleron/Merck, Altavant, Aerovate, Pharmosa/Liquidia, Actelion/Janssen, Lung LLC.
References
Elwing JM, Dar Vizza C, Franco V, et al. Efficacy of oral treprostinil in patients with pulmonary arterial hypertension with and without cardiovascular comorbidities. Chest 2023; 164(4 Suppl):A5883-A5885. doi:https://doi.org/10.1016/j.chest.2023.07.3790
Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension [published correction appears in Eur Heart J 2023; 44(15):1312]. Eur Heart J 2022; 43(38):3618-3731. doi:10.1093/eurheartj/ehac237
White RJ, Jerjes-Sanchez C, Bohns Meyer GM, et al; FREEDOM-EV Investigators. Combination therapy with oral treprostinil for pulmonary arterial hypertension. A double-blind placebo-controlled clinical trial. Am J Respir Crit Care Med 2020; 201(6):707-717. doi:10.1164/rccm.201908-1640OC