Safety and Efficacy of Ambrisentan-Phosphodiesterase Type 5 (PDE5) Inhibitor Combination Therapy for Japanese Pulmonary Arterial Hypertension Patients in Real-World Clinical Practice.

Background: This retrospective study was conducted to evaluate the safety and efficacy of ambrisentan combination therapy with phosphodiesterase type 5 (PDE5) inhibitors in Japanese patients with pulmonary arterial hypertension (PAH). Methods and Results: PAH patients who received ambrisentan for the first time in combination with a PDE5 inhibitor between January 2013 and the end of August 2015 were included in this study. Adverse drug reaction (ADR) safety analysis, as well as the efficacy analysis focusing on changes in clinical parameters, were investigated for overall cases and cases stratified by patient background. Forty-eight consecutive patients (n=21, 43.8% with idiopathic PAH; male/female, 18/30; average age, 43.3±17.4 years; World Health Organization functional class III/IV, n=22, 45.8%) who were treated with ambrisentan and a PDE5 inhibitor in Japan underwent the safety analysis. A total of 14 ADR occurred in 10 patients (20.8%). ADR included headache (8.3%), face edema (4.2%), angina pectoris (2.1%), hyperemia (2.1%), dyspnea (2.1%), pulmonary hypertension (i.e., worsening of PAH, 2.1%), nausea (2.1%), hepatic function abnormal (2.1%), edema (2.1%), and sudden death (2.1%). On analysis of hemodynamics parameters, there was a significant improvement in the mean pulmonary arterial pressure (-13.5 mmHg, P=0.0001) and pulmonary vascular resistance (-563.53 dyn·s·cm-5, P=0.0033). Conclusions: Ambrisentan combination therapy is safe and effective in hemodynamics improvement.