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TOPLINE:

The presence of cardiovascular comorbidities has minimal effect on the efficacy of inhaled or oral treprostinil when used alongside oral monotherapy in patients with pulmonary arterial hypertension (PAH).

METHODOLOGY:

• Researchers conducted a post hoc analysis of two phase 3 trials (TRIUMPH and FREEDOM-EV) to evaluate whether comorbid conditions influence the efficacy and tolerability of inhaled or oral treprostinil when added to oral monotherapy in patients with PAH, with or without cardiovascular comorbidities.
• Overall, 235 patients from the TRIUMPH study who received inhaled treprostinil in combination with oral monotherapy and 690 patients from the FREEDOM-EV study who received oral treprostinil alongside oral monotherapy were included in the analysis.
• Patients in both groups were stratified on the basis of the presence of zero, one or more, and two or more cardiovascular comorbidities, including atrial fibrillation, coronary artery disease, diabetes, heart failure, hypercholesterolemia, hypertension, obesity, and smoking history.
• TRIUMPH assessed improvement in exercise capacity as measured by the 6-minute walk distance and change in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels from baseline to week 12, and FREEDOM-EV evaluated the proportion of patients experiencing clinical worsening.
• For both trials, safety was also assessed in terms of adverse events (AEs).

TAKEAWAY:

• In the TRIUMPH study, the 6-minute walk distance improved significantly at 12 weeks in patients with zero (26.0 m; P = .020), one or more (22.0 m; P = .006), and two or more (21.6 m; P = .043) comorbidities receiving inhaled treprostinil compared with placebo.
• Similarly, significant reductions in the levels of NT-proBNP were observed in patients with zero (−231.0 pg/mL; P = .03), one or more (−230.5 pg/mL; P = .007), and two or more (−401.5 pg/mL; P = .005) comorbidities receiving inhaled treprostinil compared with placebo.
• In the FREEDOM-EV study, the risk for clinical worsening was lower across patient groups with zero (36%; P = .034), one or more (41%; P = .014), and two or more (45%; P = .026) comorbidities receiving oral treprostinil than for those receiving placebo.
• AE profiles remained consistent across all comorbidity groups in both TRIUMPH and FREEDOM-EV trials; however, in both trials, a greater number of patients treated with inhaled or oral treprostinil than those treated with placebo discontinued treatment due to AEs.

IN PRACTICE:

“Results from this post hoc analysis suggest that sequential combination therapy with oral or inhaled treprostinil and another background PAH therapy may also be a treatment option for this patient population with cardiovascular comorbidities,” the authors wrote.

SOURCE:

The study was led by R. James White, MD, PhD, University of Rochester Medical Center, Rochester, New York. It was published online on November 29, 2024, in CHEST.

LIMITATIONS:

The study did not include low diffusing capacity of the lungs for carbon monoxide as a comorbid condition, limiting the ability to fully characterize the patient population. Additionally, in the FREEDOM-EV study, patients with three or more risk factors for left ventricular disease were excluded, potentially limiting the applicability to individuals with a greater burden of cardiovascular comorbidities.

DISCLOSURES:

This study was supported by the United Therapeutics Corporation. Several authors reported receiving speaker fees, consulting fees, honoraria, travel and accommodation, support for scientific meetings, and research funding and serving on advisory boards or as consultants for various pharmaceutical organizations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.