Pulmonology

ERA Agonist May Be an Effective Add-On for PAH Patients

Ambrisentan, a selective endothelin-A specific receptor antagonist (ERA), may be an effective adjunctive therapy for patients with pulmonary arterial hypertension who inadequately respond to phosphodiesterase-5 inhibitor (PDE5i) monotherapy, researchers reported.

Previous studies have suggested that combining ambrisentan and tadalafil in functional class II or III patients may be beneficial, but research has not evaluated whether ambrisentan is safe and efficacious as an add-on for patients who continue to have symptoms while receiving a PDE5i such as tadalafil.
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For the study, 33 participants who had a suboptimal response to PDE5i monotherapy were assessed using an open-label design. One group of patients received at least one dose of ambrisentan in addition to a PDE5i (tadalafil or sildenafil). Patients in the control group received placebo and then tadalafil or sildenafil.

Study participants were followed for up to 48 weeks.  Functional parameters and biomarkers were assessed through week 48, and cardiopulmonary hemodynamics were assessed at week 24. The study’s primary endpoint was change in pulmonary vascular resistance.

At week 24, researchers observed statistically significant improvements in pulmonary vascular resistance. Mean pulmonary arterial pressure and cardiac index were also evaluated, and also showed significant improvements. Improvements in secondary endpoints, including 6-minute walk distance, N-terminal pro b-type natriuretic peptide, and maintenance or improvement in WHO functional class (97% of patients), were also observed.

“The hemodynamic, functional, and biomarker improvements observed in the ATHENA-1 study suggests that the sequential addition of ambrisentan to patients not having a satisfactory response to established PDE5i monotherapy is a reasonable option,” the study’s authors concluded.

—Lauren LeBano

Reference

Shapiro S, Torres F, Feldman J, et al. Clinical and hemodynamic improvements after adding ambrisentan to background PDE5i therapy in patients with pulmonary arterial hypertension exhibiting a suboptimal therapeutic response (ATHENA-1). Respir Med. 2017;126:84-92.