Conference: 2012 International PHA Conference and Scientific Sessions
Release Date: 06.22.2012
Presentation Type: Abstracts
Shapiro S1; Gillies H2; Allard M2; Blair C2; Oudiz RJ3
1West Los Angeles VA HealthCare UCLA School of Medicine, Los Angeles, CA, USA; 2Gilead Sciences Inc., Foster City, CA, USA; 3LA Biomedical Research Institute at Harbor-UCLA, Torrance, CA, USA.
BACKGROUND: Ambrisentan is an ETA-selective endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension (PAH). ATHENA-1 was an open-label efficacy and safety study of the addition of ambrisentan therapy to PAH patients with a sub-optimal response to phosphodiesterase-5 inhibitor (PDE5i) therapy. At 24 weeks, ambrisentan was well tolerated and provided clinically relevant improvements in hemodynamic parameters (mPAP, cardiac index and PVR) and exercise ability. The 48-week data is now presented here.
METHODS: Entry criteria included WHO functional class III symptoms and a pulmonary vascular resistance (PVR) of ≥ 400 dyne.sec/cm5. Patients received 5mg ambrisentan once-daily for 4 weeks with the dose increased to 10mg once-daily for an additional 44 weeks. The 48-week endpoints include: survival; time to clinical worsening; change in WHO functional class, 6-minute walk distance (6MWD), Borg Dyspnea Index (BDI), and NT-proBNP.
RESULTS: Thirty-three subjects received ambrisentan at the start of the study. At 48 weeks the Kaplan Meier survival was 96% (95% CI: 89% to 100%) and freedom from clinical worsening (percent event free) was 80% (95% CI: 66% to 94%). Nearly all (97%) patients improved or maintained their WHO functional class through 48 weeks. At baseline, 6MWD was 362±99 m, BDI score was 3.7±2.1, and NT-proBNP was 717±618 ng/L. At 48 weeks, 6MWD (+15 m, 95% CI: -15 to 44), BDI (-0.7, 95% CI: -1.4 to +0.1), and NT-pro BNP (-35%, 95% CI: -53% to -10%) were numerically improved. The most frequent adverse events were nasal congestion, headache and upper respiratory tract infection. Eight subjects (24%) discontinued study drug due to adverse events.
CONCLUSIONS: Long term addition of ambrisentan therapy to PAH patients with a sub-optimal response to PDE5i therapy was well tolerated and demonstrated improvements in 6MWD, WHO functional class, BDI, and NT-proBNP as well as high survival rates over 48 weeks.