Letairis Helps PAH Patients Who Fail to Respond Fully to Adcirca-like Therapies

Pulmonary arterial hypertension (PAH) patients who fail to respond completely to Adcirca (tadalafil) or Viagra (sildenafil) benefit from Letairis (ambrisentan) as an add-on therapy, according to a study.

The research, “Clinical and hemodynamic improvements after adding ambrisentan to background PDE5i therapy in patients with pulmonary arterial hypertension exhibiting a suboptimal therapeutic response (ATHENA-1),” was published in the journal Respiratory Medicine.

PAH can lead to failure of the right side of the heart and premature death. Letairis, an endothelin-A specific receptor antagonist (ERA), is an approved PAH treatment. It has been found safe and effective when administered alone or with Adcirca, an oral medication that inhibits an enzyme called phosphodiesterase-5 (PDE5).

While previous studies showed the drug’s effectiveness and safety when administered in a combined form, the effect of adding Letairis to patients exhibiting a sub-optimal response to a PDE5 inhibitor therapy was unknown. A sub-optimal response means patients continue to have symptoms after therapy.

The ATHENA-1 clinical trial (NCT00617305) addressed whether a combination of Letairis and a PDE5 inhibitor would be effective.

Researchers recruited PAH patients whose symptoms continued after PDE5i therapy. The study comprised two arms: One group received at least one dose of Letairis plus an approved PDE-5 inhibitor, Adcirca or Viagra. The control group was assigned a placebo, followed by Adcirca or Viagra.

The study’s primary objective was to evaluate the two groups’ change in pulmonary vascular resistance (PVR) and hemodynamic, or blood-flow-related, parameters. Patients were evaluated for up to 48 weeks. PVR was assessed at week 24, and functional parameters and biomarkers were measured through week 48. Thirty-three patients were included in the analysis.

At week 24, patients on Letairis and a PDE-5 inhibitor showed a significant improvement in PVR and in the hemodynamic parameters of mean pulmonary arterial pressure and cardiac index. The improvements in the hemodynamic parameters at week 24 were supported by improvements in the secondary endpoints, including six-minute walk test, N-terminal pro b-type natriuretic peptide, NT-proBNP — a diagnostic marker of heart failure — and maintenance or improvement in WHO functional class in 97% of patients.

Overall, the data from the ATHENA-1 study “suggests that the sequential addition of [Letairis] to patients not having a satisfactory response to established PDE5i monotherapy is a reasonable option,” researchers wrote.