PURPOSE: Ambrisentan is a propanoic acid-class, ETA-selective endothelin receptor antagonist that has been shown to improve exercise tolerance and symptoms of pulmonary arterial hypertension (PAH) in two Phase 3 placebo-controlled studies (ARIES-1 and ARIES 2). Quality of life was assessed in these studies using the SF-36 Health Survey.
METHODS: Patients receiving blinded treatment (2.5, 5, 10 mg ambrisentan or placebo) in ARIES-1 and ARIES-2 completed a SF-36 Health Survey at baseline and week 12. The primary comparison was change from baseline for the combined ambrisentan group to placebo. Scores were analyzed using repeated measures analysis of covariance for patients with data at baseline and week 12. A sensitivity analysis of all patients, with penalties for death and premature discontinuation, was also conducted.
RESULTS: A total of 110 patients receiving placebo and 242 patients receiving ambrisentan had data at baseline and week 12; baseline scores for each scale were comparable between these groups. An increase from baseline in the ambrisentan group compared to placebo (p<0.05) was observed for the physical functioning (3.8±7.7 vs. 1.1±7.6), role-physical (6.1±10.8 vs. 1.4±10.8), vitality (4.2±9.6 vs. 1.2±9.6), and the physical component summary (3.4±8.1 vs. 0.9±8.4) scales. Similar results were observed in a sensitivity analysis that included all patients. An increase from baseline compared to placebo (p<0.05) was also observed in at least 1 ambrisentan dose group for the physical functioning, role-physical, general health, vitality, role-emotional, mental health, and physical component summary scales. The incidence of peripheral edema was slightly greater for patients receiving ambrisentan (17.2%) compared to placebo (10.6%). Ambrisentan was well-tolerated and no patients receiving ambrisentan developed aminotransferase abnormalities >3xULN.
CONCLUSION: Ambrisentan improved multiple scales of the SF-36 Health Survey in patients with PAH following 12 weeks of treatment.
CLINICAL IMPLICATIONS: Patients with PAH experience substantial physical and emotional limitations that diminish their quality of life, thereby affecting their overall health status. By improving exercise tolerance and PAH symptoms, ambrisentan may also benefit patient quality of life.
DISCLOSURE: Fernando Torres, Grant monies (from industry related sources) Guilead Pharmaceutical, Actelion, United Therapeutics, Lung Rx; Consultant fee, speaker bureau, advisory committee, etc. Guilead Pharmaceutical, Pfizer, Actelion, United Therapeutics, Enzysive; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Ambrisentan is not FDA approved at this time.