Conference: 2012 International PHA Conference and Scientific Sessions
Release Date: 06.22.2012
Presentation Type: Abstracts
Rubin LJ1; Gillies H2; Allard M2; Blair C2; Badesch DB3 on behalf of the ARIES-3 Study Group.
1. University of California San Diego, La Jolla, CA, USA
2. Gilead Sciences Inc., Foster City, CA, USA
3. University of Colorado, Denver, CO, USA
BACKGROUND: Ambrisentan (ABS) is an ETA-selective endothelin receptor antagonist approved for the treatment of Group 1 pulmonary arterial hypertension (PAH). The therapeutic effects of ABS in Group1 PAH patients have been well described. ARIES-3 is an open-label study that evaluated efficacy and safety of ABS in a diverse pulmonary hypertension patient population.
METHODS: 224 patients with pulmonary hypertension (Groups 1, 3, 4, and 5) received 48-weeks of ABS therapy (5 mg once-daily x 24 weeks, then the dose could be increased to 10 mg once-daily) in the ARIES-3 study. This exploratory post-hoc subgroup analysis examines in detail for the first time the response to ABS of Group 4 Chronic Thromboembolic Pulmonary Hypertension (CTEPH) patients compared with Group 1 PAH patients. Change from baseline through week 48 is presented using last observation carried forward imputation for missing data.
RESULTS: 29 patients had CTEPH (proximal, n=11; distal, n=18) and 139 patients had PAH. CTEPH patients were older (6316 years) than PAH patients (5015 years). Baseline characteristics were similar between subgroups. At 48 weeks, improvements in 6-minute walk distance (6MWD) were +19 m (95% CI: 0.2 to 37) in the CTEPH subgroup and +36 m (95% CI: 25 to 48) in the PAH subgroup. The decrease in B-type natriuretic peptide (BNP) was -22% (95% CI: -41% to +3%) in the CTEPH subgroup compared to -20% (95% CI: -32% to -6%) in the PAH subgroup. Improvements from baseline in Borg Dyspnea Index scores were -0.8% (95% CI: -1.2% to +0.3%) in the CTEPH subgroup compared to -0.7% (95% CI: -1.0% to -0.3%) in the PAH subgroup. Approximately 90% of patients improved or maintained their WHO functional class at week 48. Kaplan-Meier estimates of survival were 93% (95% CI: 74% to 98%) in the CTEPH and 98% (95% CI: 93% to 99%) in the PAH subgroup at week 48. Kaplan-Meier estimates of event free clinical worsening was 86% (95% CI: 66% to 94%) in the CTEPH subgroup and 85% (95% CI: 77% to 90%) in the PAH subgroup. Adverse events reported were comparable between the 2 subgroups, with peripheral edema and headache being the most common events.
CONCLUSIONS: Ambrisentan was generally well-tolerated in CTEPH patients and trends toward improvement in exercise ability and dyspnea were observed. This post-hoc analysis provides a rationale for performing larger, placebo-controlled controlled studies to determine the efficacy and safety of ambrisentan in CTEPH.