PURPOSE: Ambrisentan is a propanoic acid-class, ETA-selective endothelin receptor antagonist that has been shown to improve efficacy in two Phase 3 placebo-controlled studies (ARIES-1 and ARIES-2) of patients with pulmonary arterial hypertension (PAH). The efficacy and safety of ambrisentan was assessed in these studies for patients with idiopathic PAH (IPAH) or PAH associated with connective tissue diseases (PAH-CTD).
METHODS: Patients with IPAH (n=251) and PAH-CTD (n=124) received placebo, 2.5, 5, or 10 mg ambrisentan once-daily. These studies were powered for 6-minute walk distance (6MWD) in the overall study population; therefore, only descriptive analyses were performed to explore efficacy trends for subgroups.
RESULTS: Baseline 6MWD was 349±79 meters (m) for IPAH and 335±81 m for PAH-CTD. Baseline Borg dyspnea index (BDI) was 3.9±2.2 for IPAH and 3.8±2.3 for PAH-CTD. Similar 6MWD and BDI scores were observed at baseline for patients receiving placebo or ambrisentan in each subgroup. The placebo-adjusted increase in 6MWD at week 12 was greater for the IPAH subgroup (+58 m; 95% CI: 36 to 79) compared to the PAH-CTD subgroup (+19 m; 95% CI: -10 to 48) subgroups. In contrast, the placebo-adjusted decrease in BDI at week 12 was similar for the IPAH (-0.8; 95% CI: -1.4 to -0.19) and PAH-CTD (-1.0; 95% CI: -1.7 to -0.18) subgroups. WHO functional class deterioration was similar at week 12 for the IPAH and PAH-CTD subgroups receiving ambrisentan (2.4% and 3.7%, respectively) and less than placebo (16.5% and 20.9%, respectively). Peripheral edema was similar in the IPAH and PAH-CTD subgroups receiving ambrisentan (16.3% and 19.8%, respectively) and was slightly greater than placebo (9.4% and 14.0%, respectively). Ambrisentan was well-tolerated in both subgroups and no aminotransferase abnormalities >3xULN were observed for patients receiving ambrisentan.
CONCLUSION: Consistent trends of increased exercise capacity, decreased dyspnea, and less WHO functional class deterioration were observed with ambrisentan treatment compared to placebo in both IPAH and PAH-CTD subgroups.
CLINICAL IMPLICATIONS: Ambrisentan may be a viable treatment for patients with PAH-CTD, as well as patients with idiopathic PAH.
DISCLOSURE: David Badesch, Grant monies (from sources other than industry) National Institutes of Health; Grant monies (from industry related sources) GlaxoSmithKline, United Therapeutics / Lung Rx, Actelion, Lilly/ICOS, Encysive, Pfizer, Myogen / Gilead, CoTherix; Fiduciary position (of any organization, association, society, etc, other than ACCP Pulmonary Hypertension Association Board of Directors; American Thoracic Society Board of Directors; Consultant fee, speaker bureau, advisory committee, etc. GlaxoSmithKline, Actelion, Myogen / Gilead, Encysive, CoTherix, Pfizer, United Therapeutics, Mondno-Biotech, Biogen IDEC, PR Pharmaceuticals, Forrest Labs, Scios, Amgen, Biovale Pharmaceuticals / Clarus Health, Johnson & Johnson; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Ambrisentan