PURPOSE:Ambrisentan is an ETA-selective endothelin receptor antagonist (ERA) that is approved for the treatment of pulmonary arterial hypertension (PAH) in patients with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening. Ambrisentan has been shown to improve 6-minute walk distance (6MWD) in two Phase 3, 12-week, placebo-controlled studies (ARIES-1 and ARIES-2). ARIES-E is an ongoing, long term extension study of ARIES-1 and ARIES-2. Two-year, long-term data from the ARIES studies are presented.
METHODS:This is an integrated analysis of 383 patients who received at least 1 dose of ambrisentan (2.5, 5, or 10 mg qd) in ARIES-1, ARIES-2, or ARIES-E. Patients who received placebo in the previous studies were randomized to ambrisentan in ARIES-E. The first 24 weeks of dosing in ARIES-E was a blinded, fixed-dose period. After 24 weeks, blinded dose adjustment was permitted. Baseline was defined as the time of randomization to ambrisentan.
RESULTS:Baseline subject characteristics were as follows: 63% idiopathic PAH, 37% associated PAH. Nearly all subjects were WHO class II (43%) or WHO class III (47%). Baseline 6MWD was 347 ± 85.4 meters. Two-year data from the ARIES studies will be available in July, 2008. Assessments of exercise tolerance, PAH symptoms, survival, and safety data will be presented.
CONCLUSION:Data from this analysis will provide the most comprehensive examination of the long-term safety and efficacy of ambrisentan for the treatment of PAH.
CLINICAL IMPLICATIONS:These data may support the long-term use of ETA-selective ERAs in the treatment of PAH.
DISCLOSURE:Ronald Oudiz, Grant monies (from industry related sources) Gilead Sciences; No Product/Research Disclosure Information