Clinical and hemodynamic improvements after adding ambrisentan to background PDE5i therapy in patients with pulmonary arterial hypertension exhibiting a suboptimal therapeutic response (ATHENA-1). (May 2017) - Shapiro, Shelley
Abstract: Objective: Pulmonary arterial hypertension (PAH) is a condition which may lead to right ventricular failure and premature death. While recent data supports the initial combination of ambrisentan (a selective ERA) and tadalafil (a PDE5i) in functional class II or III patients, there is no published data describing the safety and efficacy of ambrisentan when added to patients currently receiving a PDE5i and exhibiting a suboptimal response. The ATHENA-1 study describes the safety and efficacy of the addition of ambrisentan in this patient population. Methods: PAH patients with a suboptimal response to current PDE5i monotherapy were assigned ambrisentan in an open-label fashion and evaluated for up to 48 weeks. Cardiopulmonary hemodynamics (change in PVR as primary endpoint) were evaluated at week 24 and functional parameters and biomarkers were measured through week 48. Time to clinical worsening (TTCW) and survival are also described. Results: Thirty-three subjects were included in the analysis. At week 24, statistically significant improvements in PVR (−32%), mPAP (−11%), and CI (+25%) were observed. Hemodynamic improvements at week 24 were further supported by improvements in the secondary endpoints: 6-min walk distance (+18 m), NT-proBNP (−31%), and maintenance or improvement in WHO FC in 97% of patients. Adverse events were consistent with known effects of ambrisentan. Conclusion: 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. Highlights: This study evaluates the addition of ambrisentan to patients with an unsatisfactory response to PDE5i monotherapy. The addition of ambrisentan was associated with hemodynamic, functional, and biomarker improvement compared to baseline. Significant improvements were observed in PVR (−33%), mPAP (−11%), and CI (+24%) following 24 weeks of add-on ambrisentan. At week 24, 6MWD, NT-proBNP, and WHO functional class showed improvements from baseline. Adverse events were consistent with known effects of ambrisentan, but 10% of patients discontinued because of them.